I just read Stephen Hawking's new book, The Grand Design over the weekend. I was excited to read it but I have to say that I was thoroughly disappointed. I loved The Universe in a Nutshell. I also loved Mlodinow's The Drunkards Walk. This book was supposed to explain M-Theory but it only alluded to it. I can sum up this short book as the following: Anyone who believes in God is stupid, we don't need to invoke God to explain the origin of the universe, I'd love to explain M-theory to you but you are probably a bible believing christian who believes that God literally stopped the sun for Joshua to give him an extra day in battle so you probably wouldn't understand.
My primary interest is in biology and I don't know a lot about physics. I'd love to learn but Hawking's and Mlodinow's condescending attitudes were no help.
Why the attitude? I believe that the answer is simple. Biology has a real scientific answer for the apparent design in nature. As Robert Wright points out in his brilliant book The Evolution of God, Paley was not wrong when he made his argument from design. He noticed that much like a watch has a watchmaker, life must have had a designer. It turns out that he was right. Living organisms, unlike rocks or other minerals were designed and this design may even point to a higher purpose. The designer was natural selection. Natural selection explains the apparent design we see in the natural world.
The world of physics has no equivalent. Hawking and Mlodinow present nothing equivalent to natural selection in their new book. The only way they can explain our universe that is fine tuned for human life, is to appeal to the idea that 10 to the 500th power universes (all unobservable) must somehow exist and we find ourselves in this one because it is the only one in which beings like us could evolve. This is an interesting idea, but it is just an idea. I can't believe that they started the book with "Philosophy is dead" and then, instead of laying out the science, they philosophized about how the universe did not need a creator. Maybe they are right, I don't know. But, their question is not a scientific question but a philosophical one. Natural selection explains the apparent design we see in life on earth. But, from what I got from this book M-Theory does no such thing for the universe itself. It doesn't matter how much Hawking and Mlodinow wish it were otherwise.
Saturday, September 11, 2010
Tuesday, August 17, 2010
The spongebob squarepants genome published!
In the Aug 5th issue of nature discusses the recent publication of the A. queenslandica genome. Sponges are among the very simplest multicelluar animals so if we want to ever really understand cancer we need to understand how the first multicellular animals were able to overcome it.
The one thing that stuck out the most to me was that the genome is more complex than many suspected. The sponge has a repertoire of 18000 genes including some distant homologues to genes that code for muscle tissue and neurons in vertebrates. The article quotes Douglas Erwin who claims that this kind of complexity indicates that perhaps sponges descended from more complex animals. Another indication of this is the fact that sponge phylogeny is so poorly resolved and there is even speculation that they may be paraphyletic. Perhaps, they represent the degenerate tips of a tree that is long ago extinct. This is all possible but, I think that such conclusions may be very premature. I think that the kind of complexity we find in the sponge is exactly what we should expect. The genes for the complex neuromuscular system we find in bilaterans today certainly did not come from nowhere. Their predecessors must have evolved in simpler creatures that used them in completely different ways. If this was not the case, then such systems would simply not exist.
This is a common theme in evolution. For example, the genes that comprise the vertebrate eye lurked in our common ancestor with sea squirts filling other functions about the body. Natural selection is not an inventor and it doesn't synthesize new structures out of thin air, it can only tinker with parts that are already at hand. It will be exciting as over the next several years we are able to tease out just exactly what sponges and their relatives used these genes for!
The one thing that stuck out the most to me was that the genome is more complex than many suspected. The sponge has a repertoire of 18000 genes including some distant homologues to genes that code for muscle tissue and neurons in vertebrates. The article quotes Douglas Erwin who claims that this kind of complexity indicates that perhaps sponges descended from more complex animals. Another indication of this is the fact that sponge phylogeny is so poorly resolved and there is even speculation that they may be paraphyletic. Perhaps, they represent the degenerate tips of a tree that is long ago extinct. This is all possible but, I think that such conclusions may be very premature. I think that the kind of complexity we find in the sponge is exactly what we should expect. The genes for the complex neuromuscular system we find in bilaterans today certainly did not come from nowhere. Their predecessors must have evolved in simpler creatures that used them in completely different ways. If this was not the case, then such systems would simply not exist.
This is a common theme in evolution. For example, the genes that comprise the vertebrate eye lurked in our common ancestor with sea squirts filling other functions about the body. Natural selection is not an inventor and it doesn't synthesize new structures out of thin air, it can only tinker with parts that are already at hand. It will be exciting as over the next several years we are able to tease out just exactly what sponges and their relatives used these genes for!
Saturday, June 26, 2010
Phylogenetic dataset workflow literature review
I just got done with my evolution class for the summer semester and for my final project, I wrote a paper reviewing the literature about phylogenetic dataset automation. You can download it here. Enjoy!
Sunday, June 20, 2010
Natural selection
Most natural selection is purifying selection, that is it weeds out harmful random mutations. For the most part, natural selection actually keeps things simple and just maintains what is currently in place. If there are alleles in a population and 1 does not have any fitness advantage over another, then 1 eventually taking over the population can simply be explained by a random evolutionary mechanism such as genetic drift.
Natural selection on the other hand is the only mechanism for adaptive evolutionary change. The complex adaptations we see in nature such as the vertebrate eye for example, represent the accumulation of small changes such that each were more fit than another. There is no mechanism for natural selection to see ahead, each small step had to be beneficial enough on its own to be selected for, there is no perfect archetype being strived for.
Since natural selection can only work with existing variation which must necessarily arise from random variation, it is not possible for any adaptation to simply come out of nowhere. Natural selection tinkers with existing structures to give rise to new ones.
Is there a way to reconcile the fact that in general natural selection tends to be conservative rather than creative with the fact that natural selection is the only known mechanism to generate adaptive structures? I think so. Sean Carroll explained in his book Endless Forms Most Beautiful that over evolutionary time the force of natural selection tends to reduce the number of structures while at the same time increasing their specialization. For example, if a gene is duplicated several times, the resulting redundancy will loosen the constraints of natural selection on these gene sequences. As the conservative force of natural selection pares down this redundancy, new functions will be inevitably carved out from this variation.
In other words, natural selection is not a builder or an inventor. Natural selection is a sculptor.
Natural selection on the other hand is the only mechanism for adaptive evolutionary change. The complex adaptations we see in nature such as the vertebrate eye for example, represent the accumulation of small changes such that each were more fit than another. There is no mechanism for natural selection to see ahead, each small step had to be beneficial enough on its own to be selected for, there is no perfect archetype being strived for.
Since natural selection can only work with existing variation which must necessarily arise from random variation, it is not possible for any adaptation to simply come out of nowhere. Natural selection tinkers with existing structures to give rise to new ones.
Is there a way to reconcile the fact that in general natural selection tends to be conservative rather than creative with the fact that natural selection is the only known mechanism to generate adaptive structures? I think so. Sean Carroll explained in his book Endless Forms Most Beautiful that over evolutionary time the force of natural selection tends to reduce the number of structures while at the same time increasing their specialization. For example, if a gene is duplicated several times, the resulting redundancy will loosen the constraints of natural selection on these gene sequences. As the conservative force of natural selection pares down this redundancy, new functions will be inevitably carved out from this variation.
In other words, natural selection is not a builder or an inventor. Natural selection is a sculptor.
Wednesday, June 16, 2010
Endosymbiosis
According to the endosymbiotic theory the first eukaryote was formed by the merger of 2 prokaryotes. But how did this happen? The traditional idea was that a primitive eukaryote engulfed the ancestor of our mitochondria since eukaryotes are known for phagocytosis, the abilty to engulf other cells. However, this is probably not how it happened because the ability to engulf other cells requires energy. It is now known that all eukaryotes either have mitochondria or have lost them at some point. Nick Lane contends in his book Power, Sex, Suicide that this links the origin of eukaryotes with the acquisition of mitochondria. So, before the host cell acquired mitochondria, it wasn't going around engulfing other cells. Lane suggests that perhaps these two ancient prokaryotes started out their symbiotic relationship by living in close proximity and progressed over time to one cell living inside the other.
Genetic studies suggest that the host cell was most likely a methanogen archea. These cells are anaerobic meaning they survive on sulpher and stay away from oxygen. This seems unlikely because if this were true, why did eukaryotes appear just as oxygen levels were rising? As Lane points out, more oxygen means more sulphates because oxygen reacts with sulpher from volcanoes to produce sulphates. But, as we all know, most eukaryotes thrive in the presence of oxygen. Besides, what would use would a methenogen have for mitochondria which are useless without oxygen? Lane believes that the most likely answer is that the ancestor of mitochondria had a diverse genetic toolkit. Perhaps, it had the genes for utilizing hydrogen and oxygen. Once it started supplying the hydrogen for the methanogen, it would no longer be dependent on deep sea vents and could venture off into oxygenated environments. This primitive eukaryote would have had to adapt to the oxygenated environment before the mitochondria ancestor living inside it lost its oxygen utilizing genes through disuse.
This chain of events is just one way eukaryotes could have evolved. The lesson here is that there were enough contingencies that the ascent beyond bacteria only happened once on earth in the billions of years that bacteria have populated the earth. We are truly lucky to have made it through this bottleneck. The biggest gulf in all of life is the divide between prokaryotes and eukaryotes. This gulf is much vaster than even the chasm between no life and life. We have more in common with a humble yeast cell than it does with a bacterium.
Mitochondria are the powerhouses, of the cell and without them, complex life may not even be possible. Bacteria have been around for billions of years yet, they are eternally bacteria. There are many disadvantages to maintaining mitochondria. Their genes evolve about 20 times faster than nuclear genes as they are more susceptible to mutation. Also, the genetic machinery must be maintained in each of the hundreds of mitochondria in each cell. Over time, in difference lineages, genes have migrated from the mitochondria to the nucleus. But, there is not even 1 example of a eukaryote losing all of its mitochondrial genes, therefore there must be a huge advantage to these genetic outposts. Lane argues that local control of energy production is absolutely essential. If mitochondria didn't have their own genomes, they would not be able to individually regulate energy production. Regulating hundreds of mitochondria from the nucleus would be extremely complex and it may not even be possible for such a mechanism to evolve.
Endosymbiotic theory is a beautiful illustration of the fact that the way nature solves problems aren’t always the most straightforward but reflect phylogenetic contingencies inherent to particular lineages. The merger of 2 simple prokaryotes, despite some of the disadvantages may have been the only way for complex life to evolve on earth. According to Lane, it is also why we are most likely alone in a universe full of bacteria.
Genetic studies suggest that the host cell was most likely a methanogen archea. These cells are anaerobic meaning they survive on sulpher and stay away from oxygen. This seems unlikely because if this were true, why did eukaryotes appear just as oxygen levels were rising? As Lane points out, more oxygen means more sulphates because oxygen reacts with sulpher from volcanoes to produce sulphates. But, as we all know, most eukaryotes thrive in the presence of oxygen. Besides, what would use would a methenogen have for mitochondria which are useless without oxygen? Lane believes that the most likely answer is that the ancestor of mitochondria had a diverse genetic toolkit. Perhaps, it had the genes for utilizing hydrogen and oxygen. Once it started supplying the hydrogen for the methanogen, it would no longer be dependent on deep sea vents and could venture off into oxygenated environments. This primitive eukaryote would have had to adapt to the oxygenated environment before the mitochondria ancestor living inside it lost its oxygen utilizing genes through disuse.
This chain of events is just one way eukaryotes could have evolved. The lesson here is that there were enough contingencies that the ascent beyond bacteria only happened once on earth in the billions of years that bacteria have populated the earth. We are truly lucky to have made it through this bottleneck. The biggest gulf in all of life is the divide between prokaryotes and eukaryotes. This gulf is much vaster than even the chasm between no life and life. We have more in common with a humble yeast cell than it does with a bacterium.
Mitochondria are the powerhouses, of the cell and without them, complex life may not even be possible. Bacteria have been around for billions of years yet, they are eternally bacteria. There are many disadvantages to maintaining mitochondria. Their genes evolve about 20 times faster than nuclear genes as they are more susceptible to mutation. Also, the genetic machinery must be maintained in each of the hundreds of mitochondria in each cell. Over time, in difference lineages, genes have migrated from the mitochondria to the nucleus. But, there is not even 1 example of a eukaryote losing all of its mitochondrial genes, therefore there must be a huge advantage to these genetic outposts. Lane argues that local control of energy production is absolutely essential. If mitochondria didn't have their own genomes, they would not be able to individually regulate energy production. Regulating hundreds of mitochondria from the nucleus would be extremely complex and it may not even be possible for such a mechanism to evolve.
Endosymbiotic theory is a beautiful illustration of the fact that the way nature solves problems aren’t always the most straightforward but reflect phylogenetic contingencies inherent to particular lineages. The merger of 2 simple prokaryotes, despite some of the disadvantages may have been the only way for complex life to evolve on earth. According to Lane, it is also why we are most likely alone in a universe full of bacteria.
Friday, June 4, 2010
Monday, May 24, 2010
How prosperity evolves...
I am reading Matt Ridley's latest book "The Rational Optimist: How Prosperity Evolves." Ridley argues that humans developed a capacity for trade long before the advent of agriculture. It is in our nature. There is no tribe on earth that doesn't engage in trade and commerce. He says that it is incredibly patronizing to suggest that westerners have markets and commerce and that other people's just give each other gives to lubricate social cohesion. After almost a million years of gene culture co-evolution, humans can hardly survive without trading things and ideas. A great example of this was the Tasmanians. After 1000s of years of isolation they lost all of their technology till they had no better tools than Neanderthals. Ridley points out that the capacity for advanced technology lies in the collective brain, not in individuals. Without the ability to trade with their neighbors, Tasmanians could not tap this collective brain. As a result, their technology withered and dwindled.
I am only about a 4th of the way through so more to come. Cool stuff!
I am only about a 4th of the way through so more to come. Cool stuff!
Sunday, May 16, 2010
What is the best evolutionary explanation for the existence of 2 sexes?
In hindsight, it isn’t that hard to see the benefit of 2 sexes. Even bacteria have an archaic way to recombine genes. Genetic recombination is necessary to weed out bad mutations and makes it possible for beneficial mutations arising in different individuals to end up in the same individual. However, it is not obvious how such a system can arise through the process of natural selection. Natural selection cannot plan ahead, only what is immediately beneficial can be selected for. An organism that can reproduce asexually will be able to pass on more of its genes than one that only passes on half, therefore we should expect that species should tend to lose the capacity for sexual reproduction as its benefits are long term and natural selection cannot plan ahead.
Another problem is that if we are to have genetic recombination, then why are there only 2 sexes? If a mutation arose that allowed an individual to mate with either male or female, wouldn’t such a trait be favored by natural selection since such an individual would have access to twice the mates? Overtime, this third sex would dominate; it is interesting that such a system is not widespread.
I was fascinated by Nick Lane ideas on these issues in his book Power, Sex and Suicide. Mitochondria have their own genomes and are passed on only through the maternal line. Over time, genes from the mitochondrial genome have migrated to the nucleus but no eukaryote has lost all of them. There are a core set that are always retained in the mitochondria. Lane explains that this is because local regulation of energy production on the mitochondria is very important. The micromanagement of the production of energy in each mitochondrion from the nucleus would be an extremely complex mechanism that perhaps could not evolve step by step by natural selection and that is why we don’t see it. So, like it or not, we are stuck with a separate mitochondrial genome. As such, we need a mechanism to pass on the mitochondria. That is where the 2 sexes come in. We need to have a specialized sex that is in charge of passing on the mitochondria. There are elaborate mechanisms in place in many different species to make sure that male mitochondria do not make it into the offspring. This implies that there are good reasons why the mitochondria from both parents can’t mix. Some diseases can be traced to events where these mechanisms fail and an individual has a mix from both parents. Lane believes that the mitochondrial genome has to match up with the genes that are in the nucleus. It is easier for these to match up if all of the mitochondria are the same. Regardless of the reasons, mitochondria coming from 1 parent seems to be very important. According to Lane, regardless of any benefits we may see in hindsight, without the need for a specialized sex for passing on the mitochondria, there would be no mechanism for maintaining the 2 sex paradigm we see with only rare exceptions across all eukaryotes.
Another problem is that if we are to have genetic recombination, then why are there only 2 sexes? If a mutation arose that allowed an individual to mate with either male or female, wouldn’t such a trait be favored by natural selection since such an individual would have access to twice the mates? Overtime, this third sex would dominate; it is interesting that such a system is not widespread.
I was fascinated by Nick Lane ideas on these issues in his book Power, Sex and Suicide. Mitochondria have their own genomes and are passed on only through the maternal line. Over time, genes from the mitochondrial genome have migrated to the nucleus but no eukaryote has lost all of them. There are a core set that are always retained in the mitochondria. Lane explains that this is because local regulation of energy production on the mitochondria is very important. The micromanagement of the production of energy in each mitochondrion from the nucleus would be an extremely complex mechanism that perhaps could not evolve step by step by natural selection and that is why we don’t see it. So, like it or not, we are stuck with a separate mitochondrial genome. As such, we need a mechanism to pass on the mitochondria. That is where the 2 sexes come in. We need to have a specialized sex that is in charge of passing on the mitochondria. There are elaborate mechanisms in place in many different species to make sure that male mitochondria do not make it into the offspring. This implies that there are good reasons why the mitochondria from both parents can’t mix. Some diseases can be traced to events where these mechanisms fail and an individual has a mix from both parents. Lane believes that the mitochondrial genome has to match up with the genes that are in the nucleus. It is easier for these to match up if all of the mitochondria are the same. Regardless of the reasons, mitochondria coming from 1 parent seems to be very important. According to Lane, regardless of any benefits we may see in hindsight, without the need for a specialized sex for passing on the mitochondria, there would be no mechanism for maintaining the 2 sex paradigm we see with only rare exceptions across all eukaryotes.
Sunday, May 9, 2010
Critique of evolutionary theory
for my Evolution capstone course, we are each supposed to bring in an argument against evolution which according to the professor will fall into 1 of 3 categories. I know I've heard this before but I don't remember what they were. Anyway, I'm sure most of the examples that students will bring in will be from intelligent design advocates associated with the religious right. However, according to Kenneth Miller, in his book Only a theory, many of the creationist arguments that come from the religious right were actually borrowed from the extreme academic left. Case in point, a recent book that Nature called a "misguided attack on evolution", What Darwin Got Wrong by philosopher Jerry Fodor is a great example. His central argument is that natural selection cannot tell the difference between adaptive traits and freeloader traits. I have addressed this topic at length in previous posts and I believe it is a pretty inane claim coming from such a supposedly sophisticated philosopher. I don't believe that there is a meaningful distinction between a selfish freeloading trait and a truly adaptive trait (see my last few posts on this topic.)
Another claim he makes is that evolution is a historical process and as such isn't truly testable. I like the way that Nick Lane addresses this claim in his book Life Ascending in his chapter on the evolution of the vertebrate eye. He points out that when investigating the evolution of a particular phenotype, we actually can make specific predictions. It doesn't matter that the process actually occurred long ago. The fact is, we can make predictions about how some structure evolved and we can confirm or falsify these claims as the data comes in from genome sequences and other sources. For example, we can make the claim that the vertebrate eye evolved by the process of natural selection. The common ancestor of invertebrate chordates and vertebrates did have a retina. In fact, the sea squirt today has a retina but no lens. So, to confirm this claim we would need to show that the specialized lens proteins that exist in the vertebrate eye were already present in this common ancestor. What is important to note here is that these kinds of claims are definitely falsifiable. If these apparently specialized proteins just appeared out of thin air, that would be a huge blow to natural selection. Potentially, if such a pattern emerged, then evolution by natural selection could be falsified. But, according to Lane, this is not what was found. He explains that vertebrate eye crystallin proteins were sequenced in the 80s and all of the proteins used to construct the vertebrate eye can be found in other parts of the body fulfilling other completely unrelated tasks. In fact, in the sea squirt which does not have a lens over its retina, some of these crystallin proteins are performing other functions nearby in the brain. This example is not isolated of course and there are many different ways that predictions can be made about the path that natural selection has taken which can then be tested as data becomes available. Fodor's criticism is indeed misguided.
Another claim he makes is that evolution is a historical process and as such isn't truly testable. I like the way that Nick Lane addresses this claim in his book Life Ascending in his chapter on the evolution of the vertebrate eye. He points out that when investigating the evolution of a particular phenotype, we actually can make specific predictions. It doesn't matter that the process actually occurred long ago. The fact is, we can make predictions about how some structure evolved and we can confirm or falsify these claims as the data comes in from genome sequences and other sources. For example, we can make the claim that the vertebrate eye evolved by the process of natural selection. The common ancestor of invertebrate chordates and vertebrates did have a retina. In fact, the sea squirt today has a retina but no lens. So, to confirm this claim we would need to show that the specialized lens proteins that exist in the vertebrate eye were already present in this common ancestor. What is important to note here is that these kinds of claims are definitely falsifiable. If these apparently specialized proteins just appeared out of thin air, that would be a huge blow to natural selection. Potentially, if such a pattern emerged, then evolution by natural selection could be falsified. But, according to Lane, this is not what was found. He explains that vertebrate eye crystallin proteins were sequenced in the 80s and all of the proteins used to construct the vertebrate eye can be found in other parts of the body fulfilling other completely unrelated tasks. In fact, in the sea squirt which does not have a lens over its retina, some of these crystallin proteins are performing other functions nearby in the brain. This example is not isolated of course and there are many different ways that predictions can be made about the path that natural selection has taken which can then be tested as data becomes available. Fodor's criticism is indeed misguided.
Thursday, April 29, 2010
Bioinformatic analysis of Ephemeroptera
This semester I have been creating a workflow using Taverna to help Dr. Ogden at UVU with his analysis of mayflies and dragonflies.
Taverna is a platform used to create scientific workflows. There is a drag and drop interface where existing services can be drug to the workflow and integrated with your experiment. Taverna integrates with MyExperiment which makes it easy to publish and share your workflows. Dr Ogden has a particular problem he is trying to solve with his research that has not been addressed yet using this platform so many custom components have to be developed using Java in order to complete this project. This semester, I got something working but there is still a lot of work to do.
My workflow needs to be smart enough to automatically create a merged dataset for any order specified but also flexible enough that the user can customize the way that the data set is created and analyzed. Currently, a lot of time is spent manually creating these datasets and this project will not only speed up this process but make the research more traceable and consistent.
Dr Ogden was impressed by my demo and believes that this project may be publishable. Currently, there are not workflow components out there this fill this need. If I make this workflow and the components flexible enough, then other researchers may be able to easily integrate them into their own research projects and this could potentially be a big contribution to the bioinformatics community!
Taverna is a platform used to create scientific workflows. There is a drag and drop interface where existing services can be drug to the workflow and integrated with your experiment. Taverna integrates with MyExperiment which makes it easy to publish and share your workflows. Dr Ogden has a particular problem he is trying to solve with his research that has not been addressed yet using this platform so many custom components have to be developed using Java in order to complete this project. This semester, I got something working but there is still a lot of work to do.
My workflow uses queries genbank and gets all of the sequences for the Ephemeroptera order. It then extracts the taxa and the element name from each one. There are a lot of duplicates so it then sorts these by date and gets the most recent, also if one sequence is marked as complete and another as partial it will use the complete one. For each element, if there are enough taxa for it, it will create a dataset for that element. Wingless for example only has 3 taxa so that one is skipped.
Then it does a multiple alignment for each dataset. After that, it creates a merged dataset, for all of the taxa that appear in enough of the datasets (if a given taxa doesn't appear in enough of the individual datasets it is left out.)
The next step is to do a phylogenetic analysis on the final merged dataset. I am still experimenting with how to do this. Taverna likes to do everything with webservices but this dataset is large so that might not be practical. So, it would probably be best to fire off a mr bayes or paup block on the local machine. Anyway, that part is relatively easy anyway.
Over the summer I will be experimenting with creating a slick web interface which I will design using Open Lazlo technology which is a rich web interface programming language that I have been learning on the side.
My workflow needs to be smart enough to automatically create a merged dataset for any order specified but also flexible enough that the user can customize the way that the data set is created and analyzed. Currently, a lot of time is spent manually creating these datasets and this project will not only speed up this process but make the research more traceable and consistent.
Dr Ogden was impressed by my demo and believes that this project may be publishable. Currently, there are not workflow components out there this fill this need. If I make this workflow and the components flexible enough, then other researchers may be able to easily integrate them into their own research projects and this could potentially be a big contribution to the bioinformatics community!
Monday, April 26, 2010
Alu elements and uniquely human traits
Just finished a paper about alu proliferation in primates and the connection to higher cognition in humans. I hope you like it! Download it here
Monday, April 5, 2010
Did population bottlenecks 1mya and before the great leap forward accelerate human evolution?
Here is a possible question for my paper:
Did population bottlenecks 1mya and before the great leap forward accelerate human evolution?
Han and Xing argue in their 2005 paper, Under the genomic radar, that the capacity for alu proliferation can lurk in the primate genome for millions of years. This is because a low activity variant known as a stealth driver may occasionally spawn a high activity daughter sequence. These daughter sequences and it's spawn are likely to be purged by natural selection but the parent stealth driver would be untouched. It would not be active enough itself for natural selection to even be able to see it. In this sense Alu sequences have evolved to subvert natural selection. If Hedges is correct, then even this highly active daughter sequence might be able to subvert natural selection if there is a population bottleneck. In such a bottleneck, these highly active daughter sequences would be permitted to wreak their havoc while any disastrous insertions would have to be selected out one by one. Therefore, population bottlenecks promote alu proliferation. (See my more detailed summary of these 2 articles in my previous post: Did we evolve to evolve?)
In their 2009 article "Mobile elements reveal small population size in the ancient ancestors of Homo sapiens" Huff, Rogers, et al up at the University of Utah compared the complete genomes of 2 individuals. They say that back in the 80s it was predicted that regions of the genome with a rare insertion event (such as an alu insertion) are twice as old as regions without such an event. This is true because a region with such an event has 2 sub-regions one before and one after. They observed that regions with an insertion event had twice the nucleotide diversity which confirms this idea. They determined that the average time since the most recent common ancestor for regions with an insertion event was just under a million years (half this for other regions.) By studying these regions they were able to determine which high confidence that the effective population size a million years ago was less than 26,000 and probably closer to 18,500. This surprisingly low number may be explained by a series of population bottlenecks or different competing populations of homo replacing one another.
Now, this paper used alu sequence data as a marker to determine that there was a population bottleneck a million years ago. It doesn't say anything about the possibility that this bottleneck facilitated increased alu proliferation which is what I would expect from reading Xing and Hedges. Whether or not I can connect these 2 things is something that I will have to determine.
In another 2009 paper from the U "Mobile elements create structural variation" Xing, Huff, et al show how alu proliferation can contribute to structural variation in the human genome. They compared sequences in the HuRef sequencing project to those from the human genome project. They focused on insertions and deletions that were particular to the HuRef genome so that they could identify structural variations that are polymorphic in humans. They found that as many as a third of these polymorphic alu insertions occurred within genic regions. However,all but 3 were not within exons. But as I discussed in previous posts, alu sequences within introns have been shown in some cases to regulate the expression of the parent gene so I believe these variations could potentially be significant. I have a lot of literature supporting this stuff. Also, as Wray (see previous post) argues phenotypic variation arising from regulatory changes may be more directly shapable by natural selection because they tend to be co-dominant.
My next step is to find the connection between the literature about bottlenecks facilitating proliferation and this stuff about alu sequences generating structural variation in the genome. Is there something I can test here using sequence data available on genbank? The accession numbers for the alus studied in the structural varation paper are on there, what can I do with them?
After I have connected those things, then I want to show that selection for higher cognition molded the human brain from this novel variation.
To sum up what I have to work with so far:
Rogers et al: Analyzing alu sequence insertions can tell us about past population bottlenecks
Han and Xing: The stealth driver model predicts that these bottlenecks promote alu proliferation
Xing Huff: Alu proliferation creates structural variation (This is the part that I think I will be able to do some sequence analysis. All of the alus studied in the paper are in genbank)
I have lots of material explaining how natural selection can take advantage of this varation (exonization, alternative splicing, A-I editing, etc) to build the human brain.
In connecting all of these things, I want to answer the question at the top of this post. Did past bottlenecks, accelerate alu proliferation and more importantly, was this extra variation needed to produce the human brain? Or in other words is it selection pressure which determines the outcome or is natural selection constrained by available materials?
Did population bottlenecks 1mya and before the great leap forward accelerate human evolution?
Han and Xing argue in their 2005 paper, Under the genomic radar, that the capacity for alu proliferation can lurk in the primate genome for millions of years. This is because a low activity variant known as a stealth driver may occasionally spawn a high activity daughter sequence. These daughter sequences and it's spawn are likely to be purged by natural selection but the parent stealth driver would be untouched. It would not be active enough itself for natural selection to even be able to see it. In this sense Alu sequences have evolved to subvert natural selection. If Hedges is correct, then even this highly active daughter sequence might be able to subvert natural selection if there is a population bottleneck. In such a bottleneck, these highly active daughter sequences would be permitted to wreak their havoc while any disastrous insertions would have to be selected out one by one. Therefore, population bottlenecks promote alu proliferation. (See my more detailed summary of these 2 articles in my previous post: Did we evolve to evolve?)
In their 2009 article "Mobile elements reveal small population size in the ancient ancestors of Homo sapiens" Huff, Rogers, et al up at the University of Utah compared the complete genomes of 2 individuals. They say that back in the 80s it was predicted that regions of the genome with a rare insertion event (such as an alu insertion) are twice as old as regions without such an event. This is true because a region with such an event has 2 sub-regions one before and one after. They observed that regions with an insertion event had twice the nucleotide diversity which confirms this idea. They determined that the average time since the most recent common ancestor for regions with an insertion event was just under a million years (half this for other regions.) By studying these regions they were able to determine which high confidence that the effective population size a million years ago was less than 26,000 and probably closer to 18,500. This surprisingly low number may be explained by a series of population bottlenecks or different competing populations of homo replacing one another.
Now, this paper used alu sequence data as a marker to determine that there was a population bottleneck a million years ago. It doesn't say anything about the possibility that this bottleneck facilitated increased alu proliferation which is what I would expect from reading Xing and Hedges. Whether or not I can connect these 2 things is something that I will have to determine.
In another 2009 paper from the U "Mobile elements create structural variation" Xing, Huff, et al show how alu proliferation can contribute to structural variation in the human genome. They compared sequences in the HuRef sequencing project to those from the human genome project. They focused on insertions and deletions that were particular to the HuRef genome so that they could identify structural variations that are polymorphic in humans. They found that as many as a third of these polymorphic alu insertions occurred within genic regions. However,all but 3 were not within exons. But as I discussed in previous posts, alu sequences within introns have been shown in some cases to regulate the expression of the parent gene so I believe these variations could potentially be significant. I have a lot of literature supporting this stuff. Also, as Wray (see previous post) argues phenotypic variation arising from regulatory changes may be more directly shapable by natural selection because they tend to be co-dominant.
My next step is to find the connection between the literature about bottlenecks facilitating proliferation and this stuff about alu sequences generating structural variation in the genome. Is there something I can test here using sequence data available on genbank? The accession numbers for the alus studied in the structural varation paper are on there, what can I do with them?
After I have connected those things, then I want to show that selection for higher cognition molded the human brain from this novel variation.
To sum up what I have to work with so far:
Rogers et al: Analyzing alu sequence insertions can tell us about past population bottlenecks
Han and Xing: The stealth driver model predicts that these bottlenecks promote alu proliferation
Xing Huff: Alu proliferation creates structural variation (This is the part that I think I will be able to do some sequence analysis. All of the alus studied in the paper are in genbank)
I have lots of material explaining how natural selection can take advantage of this varation (exonization, alternative splicing, A-I editing, etc) to build the human brain.
In connecting all of these things, I want to answer the question at the top of this post. Did past bottlenecks, accelerate alu proliferation and more importantly, was this extra variation needed to produce the human brain? Or in other words is it selection pressure which determines the outcome or is natural selection constrained by available materials?
Monday, March 29, 2010
the role of alu sequences in uniquely human traits
One way that alu sequences are recruited into the functional genome is through a process called exonization.
Lei and Day explain that alu elements actually contain enhancer sequences that facilitate this process.
Ha¨sler and Katharina Strub explain that many alus are found within coding regions of genes. They get there through exonization. This can happen when an alu is inserted in the middle of an intronic region resulting in a new exon. There are several possibilities for alternative splicing in this scenario. Perhaps only the alu sequence itself is included in the new exon or the portion of the intron upstream or downstream could potentially be included. Not all potential splice sites are employed at the same frequency. This is evidence of selection shaping how these genes are alternatively spliced. Another interesting thing is that in every case, some kind of alternative splicing occurs in every gene that contains an exonized alu. The addition of a new exon into a gene would probably involve a frameshift and would be presumably deleterious. So, perhaps unless the original gene is preserved through alternative splicing any new configuration is eliminated through selection.
The exonization process depends on multiple subsequent mutations. These have been mapped out in some cases by Singer and Shmitz in their paper: From Junk to Gene. I wasn't able to look at the whole article yet, because I am waiting for the interlibrary loan but they actually map out the exact sequence of steps involved in the exonization of some particular alu sequences which is pretty amazing.
Since exonization events depend on multiple successive mutations and almost all of the time there will be no benefit for the organism there would need to be a large pool of proliferating alus to draw from in order to explore all of the possibilities. The human genome contains over a million such sequences.
Another area I have been reading about is in the role of alus in RNA editing. Eisenberg explains that in addition to sometimes changing the products of mRNA transcripts, RNA editing may subtly effect the stability of the RNA molecule which in the end would effect expression.
Mattick links alu sequences to the function of memory formation in the human brain. He points out that the ADAR2 protein which is involved in RNA editing binds to alu sequences. ADAR2 is linked to cell signaling pathways involved in memory formation. Mattick believes that this may be a way that an organisms environment and an individual's experiences can shape the way memories are formed.
Gommans and Maas describe RNA editing in terms of evolvability. They argue that selection may favor systems with high levels of diversity and that the drive toward complexity may arise from the need to keep selfish elements under control. They argue that the more complex an organism is, the more resilient it is against the effects of RNA editing. This inevitably leads to tolerance and proliferation of alus that induce RNA editing. This new editing increases the complexity of the organism even more which results in a feedback loop of ascending complexity.
The debate about how much of the noncoding genome is functional is fundamentally misguided. In the case of transposable elements in general and alus in particular, all are in some sense evolutionarily successful or they would not be there at all. But are they functional? I suppose it depends on your perspective. I am reminded of Lane's musings on the troubled birth of the individual. While they generally share the same interests, even the cells in our own body cannot cooperate without mechanisms in place to force them into compliance. All of the genes and other elements in the genome also have a strong incentive to cooperate because if the organism dies then none of them are passed on. But, all elements in the genome must balance these common interests with their own individual interests and unlike rebellious cancerous cells which will never break free, selfish genetic elements are free to evolve and explore ways to pass themselves on. To survive, all elements in the genome must find ways to pass themselves on. So, if a transposable element is recruited by natural selection to perform some function, this element has not lost some kind of battle. From it's perspective, this is the best thing that can happen as being recruited to a task grants the element job security. The same thing happens when a protein coding gene is duplicated. The newly spawned gene must contribute something useful or risk being thrown out by natural selection. Whether you think of the individual in terms of a colony of cells or a group of genes, nothing noteworthy, beautiful or complex can arise without some kind of conflict among the constituent parts. Natural selection does not just magically push life toward complexity. Conflict in the genome isn't about "parasitic" sequences "invading" the genome. Rather, it is about millions of elements cooperating, if reluctantly, to form a cohesive whole. Without conflict, natural selection would have nothing to work with at all.
Lei and Day explain that alu elements actually contain enhancer sequences that facilitate this process.
Ha¨sler and Katharina Strub explain that many alus are found within coding regions of genes. They get there through exonization. This can happen when an alu is inserted in the middle of an intronic region resulting in a new exon. There are several possibilities for alternative splicing in this scenario. Perhaps only the alu sequence itself is included in the new exon or the portion of the intron upstream or downstream could potentially be included. Not all potential splice sites are employed at the same frequency. This is evidence of selection shaping how these genes are alternatively spliced. Another interesting thing is that in every case, some kind of alternative splicing occurs in every gene that contains an exonized alu. The addition of a new exon into a gene would probably involve a frameshift and would be presumably deleterious. So, perhaps unless the original gene is preserved through alternative splicing any new configuration is eliminated through selection.
The exonization process depends on multiple subsequent mutations. These have been mapped out in some cases by Singer and Shmitz in their paper: From Junk to Gene. I wasn't able to look at the whole article yet, because I am waiting for the interlibrary loan but they actually map out the exact sequence of steps involved in the exonization of some particular alu sequences which is pretty amazing.
Since exonization events depend on multiple successive mutations and almost all of the time there will be no benefit for the organism there would need to be a large pool of proliferating alus to draw from in order to explore all of the possibilities. The human genome contains over a million such sequences.
Another area I have been reading about is in the role of alus in RNA editing. Eisenberg explains that in addition to sometimes changing the products of mRNA transcripts, RNA editing may subtly effect the stability of the RNA molecule which in the end would effect expression.
Mattick links alu sequences to the function of memory formation in the human brain. He points out that the ADAR2 protein which is involved in RNA editing binds to alu sequences. ADAR2 is linked to cell signaling pathways involved in memory formation. Mattick believes that this may be a way that an organisms environment and an individual's experiences can shape the way memories are formed.
Gommans and Maas describe RNA editing in terms of evolvability. They argue that selection may favor systems with high levels of diversity and that the drive toward complexity may arise from the need to keep selfish elements under control. They argue that the more complex an organism is, the more resilient it is against the effects of RNA editing. This inevitably leads to tolerance and proliferation of alus that induce RNA editing. This new editing increases the complexity of the organism even more which results in a feedback loop of ascending complexity.
The debate about how much of the noncoding genome is functional is fundamentally misguided. In the case of transposable elements in general and alus in particular, all are in some sense evolutionarily successful or they would not be there at all. But are they functional? I suppose it depends on your perspective. I am reminded of Lane's musings on the troubled birth of the individual. While they generally share the same interests, even the cells in our own body cannot cooperate without mechanisms in place to force them into compliance. All of the genes and other elements in the genome also have a strong incentive to cooperate because if the organism dies then none of them are passed on. But, all elements in the genome must balance these common interests with their own individual interests and unlike rebellious cancerous cells which will never break free, selfish genetic elements are free to evolve and explore ways to pass themselves on. To survive, all elements in the genome must find ways to pass themselves on. So, if a transposable element is recruited by natural selection to perform some function, this element has not lost some kind of battle. From it's perspective, this is the best thing that can happen as being recruited to a task grants the element job security. The same thing happens when a protein coding gene is duplicated. The newly spawned gene must contribute something useful or risk being thrown out by natural selection. Whether you think of the individual in terms of a colony of cells or a group of genes, nothing noteworthy, beautiful or complex can arise without some kind of conflict among the constituent parts. Natural selection does not just magically push life toward complexity. Conflict in the genome isn't about "parasitic" sequences "invading" the genome. Rather, it is about millions of elements cooperating, if reluctantly, to form a cohesive whole. Without conflict, natural selection would have nothing to work with at all.
Monday, March 15, 2010
Did we evolve to evolve?
As I discussed in previous posts, ALU elements are unique to primates and the fact that their proliferation rates and transcription patterns are different in humans than other primates suggests that they may be responsible some uniquely human traits. In "Under The Genomic Radar: The stealth model of alu amplification" Han and Xing, put forward some ideas about why some subfamilies of ALUs suddenly proliferate after millions of years with no activity. They explain that the AluYa and AluYb alu subfamilies actually date back 18-26my. However, the proliferation of these sequences has only occurred in the human lineage. Since the parent sequences date much further back in the primate genome, it seems that the capacity for proliferation has been there for quite some time.
The traditional model has been that master ALU sequence continually spawns daughter sequences that proliferate throughout the genome. However, this simplistic model fails to account for the fact that proliferation rates vary widely over time and across taxa. Han and Xing explain their stealth driver model as an alternate explanation. They believe that a low activity sequence can lurk in the genome over long periods of time. Occasionally, this sequence may spawn a daughter sequence that is much more active, these daughter sequences are actually responsible for the vast majority of the activity.
These highly active daughter sequences are highly likely to be detrimental to the organism. Natural selection may weed these out, but the parent stealth driver would be invisible to natural selection so it would be allowed to persist to spawn another high activity daughter sequence in the future.
In this sense, ALU elements themselves have in fact evolved to evolve. However, there is no reason to think that they have our interests in mind. These stealth drivers lay low because they don't want to kill their hosts and end up dead themselves. But, if they lay low forever they will be drowned out by their competitors.
But when do they come out of their hiding place? According to Hedges in "Differential alu mobilization and polymorphism among human and chimp lineages" it may be that these sequences end up proliferating when natural selection is unable to weed them out. This would occur during a population bottleneck. I found this idea very intriguing because as Wray pointed out in my last post, some uniquely human characteristics may be regulated by ALU transcription in the human brain. For example, regulation of the prodynorphin gene which has roles in memory, emotional status and perception. If Hedges idea is true, then a population bottleneck 3 million years ago could have been responsible for the fact that certain subfamilies that have not expanded in other primate lineages ended up proliferating in the human lineage. Hedges explains that any deleterious ALU insertion would be selected out by natural selection. But, in a population bottleneck, natural selection may not be able to get rid of the high activity master ALU sequence itself. So, although deleterious changes would be weeded out as they appear, the sequences would continue to proliferate. The vast majority of those that persist would be either neutral or very slightly deleterious. The human lineage is known for its bushiness. This extra variation may have driven increased speciation events. Is it possible that these extra raw materials may have given rise to some unique human traits? I believe the answer might be yes.
I have a lot more on my list to read on this topic. My research has led to some papers coming from the U which is pretty cool. My goal is to shed some light on the unique path that human evolution has trod and perhaps show that whether or not it is always beneficial to the organism as a whole, selfish elements in our genome have evolved to evolve. Perhaps the friction among these rival elements are the spark that ignited human evolution.
The traditional model has been that master ALU sequence continually spawns daughter sequences that proliferate throughout the genome. However, this simplistic model fails to account for the fact that proliferation rates vary widely over time and across taxa. Han and Xing explain their stealth driver model as an alternate explanation. They believe that a low activity sequence can lurk in the genome over long periods of time. Occasionally, this sequence may spawn a daughter sequence that is much more active, these daughter sequences are actually responsible for the vast majority of the activity.
These highly active daughter sequences are highly likely to be detrimental to the organism. Natural selection may weed these out, but the parent stealth driver would be invisible to natural selection so it would be allowed to persist to spawn another high activity daughter sequence in the future.
In this sense, ALU elements themselves have in fact evolved to evolve. However, there is no reason to think that they have our interests in mind. These stealth drivers lay low because they don't want to kill their hosts and end up dead themselves. But, if they lay low forever they will be drowned out by their competitors.
But when do they come out of their hiding place? According to Hedges in "Differential alu mobilization and polymorphism among human and chimp lineages" it may be that these sequences end up proliferating when natural selection is unable to weed them out. This would occur during a population bottleneck. I found this idea very intriguing because as Wray pointed out in my last post, some uniquely human characteristics may be regulated by ALU transcription in the human brain. For example, regulation of the prodynorphin gene which has roles in memory, emotional status and perception. If Hedges idea is true, then a population bottleneck 3 million years ago could have been responsible for the fact that certain subfamilies that have not expanded in other primate lineages ended up proliferating in the human lineage. Hedges explains that any deleterious ALU insertion would be selected out by natural selection. But, in a population bottleneck, natural selection may not be able to get rid of the high activity master ALU sequence itself. So, although deleterious changes would be weeded out as they appear, the sequences would continue to proliferate. The vast majority of those that persist would be either neutral or very slightly deleterious. The human lineage is known for its bushiness. This extra variation may have driven increased speciation events. Is it possible that these extra raw materials may have given rise to some unique human traits? I believe the answer might be yes.
I have a lot more on my list to read on this topic. My research has led to some papers coming from the U which is pretty cool. My goal is to shed some light on the unique path that human evolution has trod and perhaps show that whether or not it is always beneficial to the organism as a whole, selfish elements in our genome have evolved to evolve. Perhaps the friction among these rival elements are the spark that ignited human evolution.
Monday, March 8, 2010
ALU elements and human evolution
One of the most exciting areas around noncoding sequences are the discoveries being made around ALU elements expressed in the brain. This article is a good review of the current research. A 2006 paper by Hasler and Strub "ALU elements as regulators of gene expression" in the journal Nucleic Acids Research explains that ALU elements arose exclusively in the primate lineage and are implicated in shaping the evolution of the primate brain.
ALUs have been shown to be involved in alternative splicing. They have also been shown to edit mRNAs in other ways as well. The paper talks about a process called exonization where a previously intronic sequence is recruited into the coding region of a gene. When this area includes an ALU element, there is potential for this exon to be alternatively spliced. Computational studies have confirmed that this does indeed happen.
Since ALUs evolved very recently, they all share much similarity. This makes it easier to do bioinformatic studies on them. Also, the fact that they are exclusive to the primate lineage is exciting because they may be the secret that sets humans apart.
ALUs have been shown to be involved in alternative splicing. They have also been shown to edit mRNAs in other ways as well. The paper talks about a process called exonization where a previously intronic sequence is recruited into the coding region of a gene. When this area includes an ALU element, there is potential for this exon to be alternatively spliced. Computational studies have confirmed that this does indeed happen.
Since ALUs evolved very recently, they all share much similarity. This makes it easier to do bioinformatic studies on them. Also, the fact that they are exclusive to the primate lineage is exciting because they may be the secret that sets humans apart.
Junk DNA: how much really is junk?
Junk DNA:
The question of how much of our junk DNA may turn out to be functional is a fascinating topic. I wrote a paper on this topic about 5 years ago based largely on the work of John Mattick. Mattick argues that because most of the genome is actually transcribed, and because it seems to be transcribed in a programmatic way (ie some noncoding areas are transcribed in a pattern dissimilar to adjacent genes) then most of the genome is probably functional. When I wrote the paper, I agreed with this idea but I have a more nuanced position today I think. A few weeks before I finished my report, a paper was published in nature showing that a mouse that had many noncoding regions deleted from its genome was clinically equivalent to other mice. Among the noncoding regions that were deleted from the mouse's genome were areas referred to as "ultra conserved regions." Some UCR's are more conserved in vertebrates than some of the most constant proteins. If these sequences were conserved so pristinely by natural selection, they must have a crucial function. But, this experiment seemed to show that was not the case. But, there is still a mystery here. If these sequences were not crucial for the survival of the mouse, why were they conserved over the course of 100 million years of evolution?
Going back to my notes of Power, Sex, Suicide by Nick Lane, on page 187 he talks about how the extra DNA in eukaryotes may function as raw material for new genes. Bacteria were under selection for trim genomes because fast division was important. It's not that eukaryotes are under selection for bigger genomes so that they can later evolve new genes. Natural selection cannot and does not plan ahead. Therefore, the tendency toward bigger genomes is more likely because mutations that add something, anything to the genome are more likely to be neutral than ones that delete something. Therefore, if eukaryotes are not under selection for small genomes, then they will tend to collect junk over time.
Why our 'junk DNA' may be useful after all:
Pearson, Aria New Scientist; 7/14/2007, Vol. 195 Issue 2612, p42-45, 4p
Finally a balanced and reasonable article on the subject of junk DNA. Pearson points out that we have actually known about functional noncoding DNA since the early 70s. In Mattick's writings, he accuses the scientific establishment of completely ignoring noncoding regions for decades. From what I've been reading, I don't think that this is actually the case. The reason why science has focused on coding regions in because they are better understood and mutations in them are more easily pinpointed.
The article compares junk DNA to bloatware on new computers. Some of it may appear to be doing something and appear to be functional but whether or not it is doing us any good is debatable. This is an interesting analogy and I can't help but think it must be true in many cases.
Many researchers believe that most noncoding RNAs that are transcribed are really just noise that is generated by the transcription of nearby genes. However, Gingeras argues that this can't explain a lot of non coding transcription because many non coding RNAs are transcribed in areas where there are no genes nearby. I wonder if a lot of this is like the bloatware analogy. Perhaps something is happening but that doesn't mean that whatever is happening is necessarily benefiting the organism.
One interesting observation that Mattick makes is that long noncoding RNAs transcribed in the mouse brain are transcribed differently than the genes that they are closest to. This suggests that their transcription is not an accident but must be controlled programmatically.
What this article shows is that the debate is not about whether or not any sequences outside of protein coding sequences are functional. We have known that many are for decades. The debate is about how much will end up being functional. Mattick argues that more than 50% of the genome is functional and perhaps up to 80% or 90% based on the amount of the genome that is transcribed. Other researchers put the estimate at below 5% of the genome and there are plenty in between.
This is a fascinating debate. To me it seems unlikely that Mattick is right. He cannot explain why some species such as the puffer fish can get away with such a trim genome or why some relatively simple organisms such as some species of amoeba have so much junk DNA that their genomes are actually larger than humans.
But, at the same time, even if the most conservative biologists are right, if less than 5% of the genome is functional, that is still a lot of functional non coding DNA that we don't understand yet!
This paper talks about the experiment that deleted ultra conserved regions from the mouse. One explanation that was given was that perhaps the effect of these regions is subtle. If the sequence made the mouse just 1% more likely to survive then it would be preserved. I don't like this explanation. If the effect was really that subtle, then it would be more likely to be able to evolve over time. If these sequences are more preserved then protein coding genes then subtle effects do not explain their preservation.
Another explanation given by Kelly Frazer is that redundancy could be built in and there were other regions that compensated for the ones that were deleted. I don't like this explanation either. If there really is this much redundancy then how could the region be more conserved than protein coding genes? I don't see how natural selection could keep these regions so pristine if there is redundancy in the system.
This is a great mystery to me because I don't agree with any of the explanations put forward. There are many potential angles for my thesis here.
Sean Carroll:
Scientific American May 2008: Regulating Evolution
This article in Scientific American by one of my favorite authors Sean Carroll (Endless Forms Most Beautiful) explores the evolution of "enhancers" which he refers to as "switches." Eukaryotes uniquely promote transcription of their genes through these switches which can appear long before, long after or even with in introns! They are hard to detect experimentally which is why many genetic mutations have been determined to be regulatory in nature even though the exact mutation remains elusive.
The article explores some examples of phenotypes that can be modified by these regulatory sequences without affecting how the gene is expressed in other parts of the body or in other life stages.
One of the main source articles that Carroll references is Wray's paper in nature which I review below:
Gregory Wray: March 2007 Nature Reviews Genetics The evolutionary Significance of cis-regulatory mutations
Wray argues that cis-regulatory and protein coding mutations may be phenotypically distinct. He gives 2 reasons for this.
1. Each allele in a diploid organism is transcribed independently. Therefore, mutations in regulatory regions tend to be co-dominant whereas structural mutations may not be visible to natural selection till genetic drift takes place to the point where there are significant numbers organisms homozygous for the mutation.
2. Cis-regulatory mutations may only affect the organism in particular tissue or life stage whereas structural mutation will affect organism everywhere protein is expressed. There is potential for alternative splicing to cushion this affect but clear examples of this are rare.
One example he discusses is lactose tolerance in adults in northern Europeans. The switch that enabled this was actually located inside a intron in the gene that was affected. This is interesting because Mattick talks a lot about the potential for introns to evolve function. This is a great example of one that did.
Another example comes from comparisons of microarrays of gene expression in the brains of humans and chimps. The levels are expression are different for more than 10% of the genes that are expressed. The author points out that this is actually probably an underestimate. It is unknown where in the genome the regulatory sequences that affected this expression is encoded. Mattick has argued that trans-regulation may be at work, that is regulatory sequences no where near the genes being expressed.
Another example is the increased expression of prodynorphin in humans relative to other primates. This gene is involved in emotional status and perception of pain. A mutation in the regulatory sequence of this gene is responsible for the increased expression in humans.
I have a lot of material to digest here. There are a lot of angles I can take this. Mattick may be wrong that most of the genome is functional, but from what I am reading that may not matter. Even if only a small percentage is functional that doesn't change the fact that noncoding sequences may be the main drivers of eukaryotic evolution.
The question of how much of our junk DNA may turn out to be functional is a fascinating topic. I wrote a paper on this topic about 5 years ago based largely on the work of John Mattick. Mattick argues that because most of the genome is actually transcribed, and because it seems to be transcribed in a programmatic way (ie some noncoding areas are transcribed in a pattern dissimilar to adjacent genes) then most of the genome is probably functional. When I wrote the paper, I agreed with this idea but I have a more nuanced position today I think. A few weeks before I finished my report, a paper was published in nature showing that a mouse that had many noncoding regions deleted from its genome was clinically equivalent to other mice. Among the noncoding regions that were deleted from the mouse's genome were areas referred to as "ultra conserved regions." Some UCR's are more conserved in vertebrates than some of the most constant proteins. If these sequences were conserved so pristinely by natural selection, they must have a crucial function. But, this experiment seemed to show that was not the case. But, there is still a mystery here. If these sequences were not crucial for the survival of the mouse, why were they conserved over the course of 100 million years of evolution?
Going back to my notes of Power, Sex, Suicide by Nick Lane, on page 187 he talks about how the extra DNA in eukaryotes may function as raw material for new genes. Bacteria were under selection for trim genomes because fast division was important. It's not that eukaryotes are under selection for bigger genomes so that they can later evolve new genes. Natural selection cannot and does not plan ahead. Therefore, the tendency toward bigger genomes is more likely because mutations that add something, anything to the genome are more likely to be neutral than ones that delete something. Therefore, if eukaryotes are not under selection for small genomes, then they will tend to collect junk over time.
Why our 'junk DNA' may be useful after all:
Pearson, Aria New Scientist; 7/14/2007, Vol. 195 Issue 2612, p42-45, 4p
Finally a balanced and reasonable article on the subject of junk DNA. Pearson points out that we have actually known about functional noncoding DNA since the early 70s. In Mattick's writings, he accuses the scientific establishment of completely ignoring noncoding regions for decades. From what I've been reading, I don't think that this is actually the case. The reason why science has focused on coding regions in because they are better understood and mutations in them are more easily pinpointed.
The article compares junk DNA to bloatware on new computers. Some of it may appear to be doing something and appear to be functional but whether or not it is doing us any good is debatable. This is an interesting analogy and I can't help but think it must be true in many cases.
Many researchers believe that most noncoding RNAs that are transcribed are really just noise that is generated by the transcription of nearby genes. However, Gingeras argues that this can't explain a lot of non coding transcription because many non coding RNAs are transcribed in areas where there are no genes nearby. I wonder if a lot of this is like the bloatware analogy. Perhaps something is happening but that doesn't mean that whatever is happening is necessarily benefiting the organism.
One interesting observation that Mattick makes is that long noncoding RNAs transcribed in the mouse brain are transcribed differently than the genes that they are closest to. This suggests that their transcription is not an accident but must be controlled programmatically.
What this article shows is that the debate is not about whether or not any sequences outside of protein coding sequences are functional. We have known that many are for decades. The debate is about how much will end up being functional. Mattick argues that more than 50% of the genome is functional and perhaps up to 80% or 90% based on the amount of the genome that is transcribed. Other researchers put the estimate at below 5% of the genome and there are plenty in between.
This is a fascinating debate. To me it seems unlikely that Mattick is right. He cannot explain why some species such as the puffer fish can get away with such a trim genome or why some relatively simple organisms such as some species of amoeba have so much junk DNA that their genomes are actually larger than humans.
But, at the same time, even if the most conservative biologists are right, if less than 5% of the genome is functional, that is still a lot of functional non coding DNA that we don't understand yet!
This paper talks about the experiment that deleted ultra conserved regions from the mouse. One explanation that was given was that perhaps the effect of these regions is subtle. If the sequence made the mouse just 1% more likely to survive then it would be preserved. I don't like this explanation. If the effect was really that subtle, then it would be more likely to be able to evolve over time. If these sequences are more preserved then protein coding genes then subtle effects do not explain their preservation.
Another explanation given by Kelly Frazer is that redundancy could be built in and there were other regions that compensated for the ones that were deleted. I don't like this explanation either. If there really is this much redundancy then how could the region be more conserved than protein coding genes? I don't see how natural selection could keep these regions so pristine if there is redundancy in the system.
This is a great mystery to me because I don't agree with any of the explanations put forward. There are many potential angles for my thesis here.
Sean Carroll:
Scientific American May 2008: Regulating Evolution
This article in Scientific American by one of my favorite authors Sean Carroll (Endless Forms Most Beautiful) explores the evolution of "enhancers" which he refers to as "switches." Eukaryotes uniquely promote transcription of their genes through these switches which can appear long before, long after or even with in introns! They are hard to detect experimentally which is why many genetic mutations have been determined to be regulatory in nature even though the exact mutation remains elusive.
The article explores some examples of phenotypes that can be modified by these regulatory sequences without affecting how the gene is expressed in other parts of the body or in other life stages.
One of the main source articles that Carroll references is Wray's paper in nature which I review below:
Gregory Wray: March 2007 Nature Reviews Genetics The evolutionary Significance of cis-regulatory mutations
Wray argues that cis-regulatory and protein coding mutations may be phenotypically distinct. He gives 2 reasons for this.
1. Each allele in a diploid organism is transcribed independently. Therefore, mutations in regulatory regions tend to be co-dominant whereas structural mutations may not be visible to natural selection till genetic drift takes place to the point where there are significant numbers organisms homozygous for the mutation.
2. Cis-regulatory mutations may only affect the organism in particular tissue or life stage whereas structural mutation will affect organism everywhere protein is expressed. There is potential for alternative splicing to cushion this affect but clear examples of this are rare.
One example he discusses is lactose tolerance in adults in northern Europeans. The switch that enabled this was actually located inside a intron in the gene that was affected. This is interesting because Mattick talks a lot about the potential for introns to evolve function. This is a great example of one that did.
Another example comes from comparisons of microarrays of gene expression in the brains of humans and chimps. The levels are expression are different for more than 10% of the genes that are expressed. The author points out that this is actually probably an underestimate. It is unknown where in the genome the regulatory sequences that affected this expression is encoded. Mattick has argued that trans-regulation may be at work, that is regulatory sequences no where near the genes being expressed.
Another example is the increased expression of prodynorphin in humans relative to other primates. This gene is involved in emotional status and perception of pain. A mutation in the regulatory sequence of this gene is responsible for the increased expression in humans.
I have a lot of material to digest here. There are a lot of angles I can take this. Mattick may be wrong that most of the genome is functional, but from what I am reading that may not matter. Even if only a small percentage is functional that doesn't change the fact that noncoding sequences may be the main drivers of eukaryotic evolution.
Monday, March 1, 2010
Junk DNA and the foundation of eukaryotic complexity
I've been considering some new ideas for my capstone thesis. In 2004 for my science writing class, I wrote a paper about the possible function of Junk DNA. You can download and read my paper here. I was reluctant to post it because when I reread it now I don't necessarily agree with all of the conclusions that I came to. Now, I think that the idea that most junk DNA is regulatory is probably just wrong. I argued that biological complexity scales better with genome size than with gene count and that perhaps some junk DNA has a regulatory function. I explored the potential roles that micro RNAs, RNA interference and introns might play in the specification of complexity in higher eukaryotes. My main reference was the work of John Mattick who argued that the genome may contain regulatory networks he called Endogenous Controlled Multitasking. I just did a search on him on nature.com and he has done a lot more work since I last looked at him mostly in the area of micro RNAs. This week, I am going to spend some time catching up on this stuff. I think it has a great potential to turn into my thesis. Even though my original idea might have been wrong, this is still a hot area. Perhaps a small percentage of junk DNA is functional. It doesn't all have to be functional for this to be an interesting area for study!
Sunday, February 21, 2010
Further reading
I have been reading some journal articles referenced in the back of Power, Sex, Suicide under further reading to get some more background on Lane's mitochondrial aging ideas. Here's a short summary of what I have so far:
"Living Fast, Dying When?" Article from Waltham International Symposium
This article investigates evidence that correlates metabolic rate with aging. Argues that rise in resting metabolic rate extends life (decoupling in Lane’s book) while rise in nonresting rate decreases lifespan.
"Uncoupled and Surviving" From Journal Aging Cell 2004
This article studies mice with varying levels of metabolism and argues that those with more uncoupling live longer. However, from reading the article it appears that trying to infer rate of uncoupling would be technically very difficult. I will have to do some more research to find out if it is possible.
"Aging Studies On Bats: A Revew" From Biogerontology 2004
This article discusses bats as a model for aging studies. I haven't finished this one yet but it has some good potential. Bats have longer life stages similar to primates and they share flight with birds. It is interesting that they also put off aging.
"Living Fast, Dying When?" Article from Waltham International Symposium
This article investigates evidence that correlates metabolic rate with aging. Argues that rise in resting metabolic rate extends life (decoupling in Lane’s book) while rise in nonresting rate decreases lifespan.
"Uncoupled and Surviving" From Journal Aging Cell 2004
This article studies mice with varying levels of metabolism and argues that those with more uncoupling live longer. However, from reading the article it appears that trying to infer rate of uncoupling would be technically very difficult. I will have to do some more research to find out if it is possible.
"Aging Studies On Bats: A Revew" From Biogerontology 2004
This article discusses bats as a model for aging studies. I haven't finished this one yet but it has some good potential. Bats have longer life stages similar to primates and they share flight with birds. It is interesting that they also put off aging.
Tuesday, February 9, 2010
Lane himself weighs in!
After discussing my human hairlessness idea with my professor last night, I sent the following email to Dr Lane last night asking what he thought about it and whether or not it made sense:
Dr Lane,
I am an undergrad at Utah Valley University studying bioinformatics and a big fan of your books! Last year, one of my professors turned me on to Life Ascending I couldn't put it down. I am trying to nail down a topic for an undergraduate thesis and I have an idea from Power, Sex, Suicide and was was curious whether or not you or anyone else has ever thought about this and if it makes sense in the first place.
I have been looking into the issue of human hairlessness. In this months issue of Scientific American Jablanski argues that a combination of hairlessness and specialized sweat glands evolved to prevent overheating while chasing down prey on open savanna.
At the end of Power, Sex, Suicide, you talk about the fact that humans already live several times longer than we should for our size and suggest that perhaps similar to birds, but not to the same extent, we may have already increased our lifespan by increasing our mitochondrial capacity and increasing our sensitivity to free radical signalling.
You suggest that this selection possibly occurred because extended lifespan enabled elders to pass on important information to their descendants.
If this is true, then wouldn't it follow that humans are generating more heat? I know there are debates in the literature about whether or not the heat of the open savanna would be enough to explain the evolution of hairlessness in humans. What I am wondering, is if your idea that humans may have increased mitochondrial capacity may have tipped the scales in favor of hairlessness because of the combination of extra heat generated by increased mitochondrial capacity and the heat of the open savanna.
So, I am wondering if linking these 2 things makes any sense at all. As you mention in your book birds do have a slightly higher body temperature because of their higher capacity. Does it make sense to assume that humans generate slightly more heat than other mammals of similar size and as such would have more of a reason to go hairless?
Dr Lane's response:
That's a very interesting idea. The short answer is it certainly makes sense as an idea, but I've never heard of any data that would support it. But all that means is that I think the body temperature of a gorilla is around 37C, as is our own. And as you say, we would lose more heat than a gorilla simply because we are hairless, and so it follows that they would be the same.
Excellent idea! How to test it? I suppose you'd need accurate information on mitochondrial density in different tissues; ideally the level of uncoupling (possibly similar if the difference in heat production comes down to mito density, where all mitos are leaking at the same rate); rate of heat transfer across the skin with or without hair at say 40 degrees; and body temperature (again, I assume it would be similar but the rate of heat production and heat transfer would be different). I suppose other factors might be prevailing wind, height, etc - climatic factors that might alter heat transfer, and which you might take into consideration in terms of the geography of where and when modern hairless humans evolved. Also, any info on lifespan would be useful is australopithecines vs homo sapiens, etc.
I doubt that you could track down much of this information in the time available for your project, but you can probably discuss it all in an open-ended way, and take a stab at realistic values where possible.
Good luck! Best wishes
Nick
Dr Lane,
I am an undergrad at Utah Valley University studying bioinformatics and a big fan of your books! Last year, one of my professors turned me on to Life Ascending I couldn't put it down. I am trying to nail down a topic for an undergraduate thesis and I have an idea from Power, Sex, Suicide and was was curious whether or not you or anyone else has ever thought about this and if it makes sense in the first place.
I have been looking into the issue of human hairlessness. In this months issue of Scientific American Jablanski argues that a combination of hairlessness and specialized sweat glands evolved to prevent overheating while chasing down prey on open savanna.
At the end of Power, Sex, Suicide, you talk about the fact that humans already live several times longer than we should for our size and suggest that perhaps similar to birds, but not to the same extent, we may have already increased our lifespan by increasing our mitochondrial capacity and increasing our sensitivity to free radical signalling.
You suggest that this selection possibly occurred because extended lifespan enabled elders to pass on important information to their descendants.
If this is true, then wouldn't it follow that humans are generating more heat? I know there are debates in the literature about whether or not the heat of the open savanna would be enough to explain the evolution of hairlessness in humans. What I am wondering, is if your idea that humans may have increased mitochondrial capacity may have tipped the scales in favor of hairlessness because of the combination of extra heat generated by increased mitochondrial capacity and the heat of the open savanna.
So, I am wondering if linking these 2 things makes any sense at all. As you mention in your book birds do have a slightly higher body temperature because of their higher capacity. Does it make sense to assume that humans generate slightly more heat than other mammals of similar size and as such would have more of a reason to go hairless?
Dr Lane's response:
That's a very interesting idea. The short answer is it certainly makes sense as an idea, but I've never heard of any data that would support it. But all that means is that I think the body temperature of a gorilla is around 37C, as is our own. And as you say, we would lose more heat than a gorilla simply because we are hairless, and so it follows that they would be the same.
Excellent idea! How to test it? I suppose you'd need accurate information on mitochondrial density in different tissues; ideally the level of uncoupling (possibly similar if the difference in heat production comes down to mito density, where all mitos are leaking at the same rate); rate of heat transfer across the skin with or without hair at say 40 degrees; and body temperature (again, I assume it would be similar but the rate of heat production and heat transfer would be different). I suppose other factors might be prevailing wind, height, etc - climatic factors that might alter heat transfer, and which you might take into consideration in terms of the geography of where and when modern hairless humans evolved. Also, any info on lifespan would be useful is australopithecines vs homo sapiens, etc.
I doubt that you could track down much of this information in the time available for your project, but you can probably discuss it all in an open-ended way, and take a stab at realistic values where possible.
Good luck! Best wishes
Nick
Sunday, February 7, 2010
The naked truth
Why are humans hairless? An article in the journal of Zoology: Evolution of nakedness in Homo sapiens by Rantala puts forth quote a few ideas and their associated weaknesses. You can access the whole article in full here. Here are some of the ideas in the article:
The cooling device hypothesis:
We lost our hair to help us cool down in dry savannas. However Rantala argues that in the day time exposed skin actually receives more solar energy. Also increases perspiration which may cause dehydration which is very bad in savanna. He points out that savanna monkeys actually have increased hair coverage which is what we should expect.
The hunting hypothesis (otherwise known as running hypothesis)
This one says that carnivorous hominids would need to go hairless because they have to chase down their prey. Other primates (presumably these savanna monkeys) are vegetarians and don’t have to move as fast. But again, this hypothesis once again assumes that naked skin is really a good way to cool down (there must be evidence that it is if so many accept this.) Also, if this were true, and males were the hunters, why are females even more hairless?
Allometry hypothesis:
Not all organs increase in the same proportions as animals get bigger. Since humans evolved from smaller apes, the hair got sparser and as it did, sweat became the new coolant and fur became useless. The problem with this one is that gorillas hairs are further apart but they have a thick luxurious coat.
The vestiary hypothesis:
Hairlessness evolved alongside bigger brains and culture which allowed us to use clothing to regulate heat. Rantala doesn't like this one either because he believes that it's also based on faulty cooling factor.
Neoteny hypothesis:
Humans are juvenilized apes and hairlessness was just part of that package. Richard Dawkins points out in his new book "The Greatest Show On Earth" that adult humans share many features with juvenile apes. Perhaps hairlessness came with that package? This is unlikely because not all juvenile ape features are beneficial and natural selection has only retained the beneficial ones.
Adaptation against ectoparasites hypothesis:
One problem with a parasite hypothesis is that all apes have problems with parasites. What makes humans so special? Well the answer is that As humans began to establish base camps, fleas and other parasites became a bigger problem. Diseases caused by these parasites would have had strong selective pressure toward naked skin. Alan Rogers (University of Utah) did some research on the evolution of skin color (MC1R gene) and dates darker skin to about 1.2 million years ago. This is consistent with the time we started to occupy base camps.
The parasite idea is the one that the author likes best. It makes sense and I am sure that there is at least some truth to it. However, I believe that Rantala is mistaken about naked skin being a bad way to cool the body. Dennis Bramble at the University of Utah has been researching on this topic for a while. Here is a paper on The Evolution of Marathon Running. Bramble's research shows that on a hot day, a human could out compete a horse in a marathon. I think the problem with Rantala is that he does not account for our specialized sweat glands which are much different than other primates.
I think that there is probably truth to the parasite idea and the running idea. However, I don't think that these things themselves are the whole story. In my previous "tying it all together" post I have talked about Lane's idea that perhaps humans have increased mitochondrial capacity which was selected for to increase lifespan because of the knowledge advantages that elders provide. Raising internal heat generation lowers free radical formation at rest which in turn increases lifespan. If this is true, then this could make overheating a bigger problem. So far, I can't find any literature linking increased mitochondrial capacity to human hairlessness but I think it is certainly possible. This is an exciting possible angle for my thesis!
The cooling device hypothesis:
We lost our hair to help us cool down in dry savannas. However Rantala argues that in the day time exposed skin actually receives more solar energy. Also increases perspiration which may cause dehydration which is very bad in savanna. He points out that savanna monkeys actually have increased hair coverage which is what we should expect.
The hunting hypothesis (otherwise known as running hypothesis)
This one says that carnivorous hominids would need to go hairless because they have to chase down their prey. Other primates (presumably these savanna monkeys) are vegetarians and don’t have to move as fast. But again, this hypothesis once again assumes that naked skin is really a good way to cool down (there must be evidence that it is if so many accept this.) Also, if this were true, and males were the hunters, why are females even more hairless?
Allometry hypothesis:
Not all organs increase in the same proportions as animals get bigger. Since humans evolved from smaller apes, the hair got sparser and as it did, sweat became the new coolant and fur became useless. The problem with this one is that gorillas hairs are further apart but they have a thick luxurious coat.
The vestiary hypothesis:
Hairlessness evolved alongside bigger brains and culture which allowed us to use clothing to regulate heat. Rantala doesn't like this one either because he believes that it's also based on faulty cooling factor.
Neoteny hypothesis:
Humans are juvenilized apes and hairlessness was just part of that package. Richard Dawkins points out in his new book "The Greatest Show On Earth" that adult humans share many features with juvenile apes. Perhaps hairlessness came with that package? This is unlikely because not all juvenile ape features are beneficial and natural selection has only retained the beneficial ones.
Adaptation against ectoparasites hypothesis:
One problem with a parasite hypothesis is that all apes have problems with parasites. What makes humans so special? Well the answer is that As humans began to establish base camps, fleas and other parasites became a bigger problem. Diseases caused by these parasites would have had strong selective pressure toward naked skin. Alan Rogers (University of Utah) did some research on the evolution of skin color (MC1R gene) and dates darker skin to about 1.2 million years ago. This is consistent with the time we started to occupy base camps.
The parasite idea is the one that the author likes best. It makes sense and I am sure that there is at least some truth to it. However, I believe that Rantala is mistaken about naked skin being a bad way to cool the body. Dennis Bramble at the University of Utah has been researching on this topic for a while. Here is a paper on The Evolution of Marathon Running. Bramble's research shows that on a hot day, a human could out compete a horse in a marathon. I think the problem with Rantala is that he does not account for our specialized sweat glands which are much different than other primates.
I think that there is probably truth to the parasite idea and the running idea. However, I don't think that these things themselves are the whole story. In my previous "tying it all together" post I have talked about Lane's idea that perhaps humans have increased mitochondrial capacity which was selected for to increase lifespan because of the knowledge advantages that elders provide. Raising internal heat generation lowers free radical formation at rest which in turn increases lifespan. If this is true, then this could make overheating a bigger problem. So far, I can't find any literature linking increased mitochondrial capacity to human hairlessness but I think it is certainly possible. This is an exciting possible angle for my thesis!
Friday, February 5, 2010
The blank slate
I bought Steven Pinker's book The Blank Slate: The Modern Denial of Human Nature last semester when researching a paper about cultural evolution. I only had time to flip through it but didn't have time to read it. But, it just barely came out in audio so now I am listening to it. It's an important topic because we could never understand human evolution if we don't acknowledge human nature. Pinker's main assertion is that political radicals in academia push this idea about the human brain being a blank slate devoid of innate structure that is molded only by experience and social interaction and that these ideas have bled over into the hard sciences. This idea is really a secular religion based on the philosophy of Marx since there is no scientific reason to assume that we aren't born with innate faculties.
One problem so far is that the name seems to be somewhat of a straw man. I don't think that everyone he criticizes really believes that the brain has no innate structure at all. He seems very offended about the biological determinist straw man that the other side uses to paint him and I can't help but think that maybe he is doing the same thing at least to some extent. However, I know that the kind of people he talks about exist. I have had some really lefty professors that didn't seem to understand how evolution works always deferring to Gould on the topic and really fit into this blank slate mentality Pinker is talking about.
Also, Pinker seems to want it both ways which makes things confusing. He repeatedly defends the writings of Herrnstein (The Bell Curve) then elsewhere says that race need not be invoked to explain differences among groups.
One problem so far is that the name seems to be somewhat of a straw man. I don't think that everyone he criticizes really believes that the brain has no innate structure at all. He seems very offended about the biological determinist straw man that the other side uses to paint him and I can't help but think that maybe he is doing the same thing at least to some extent. However, I know that the kind of people he talks about exist. I have had some really lefty professors that didn't seem to understand how evolution works always deferring to Gould on the topic and really fit into this blank slate mentality Pinker is talking about.
Also, Pinker seems to want it both ways which makes things confusing. He repeatedly defends the writings of Herrnstein (The Bell Curve) then elsewhere says that race need not be invoked to explain differences among groups.
Monday, February 1, 2010
Tying it all together
So, do our mitochondria really kill us in the end? According to the mitochondrial theory of aging, we should expect to find cells full of worn out mitochondria as we grow old. Lane says that this is not what we find. Worse, most of the diseases associated with aging have been linked to nuclear genes.
However, Lane goes on to explain that as mitochondria become damaged through mutation they are displaced by healthy ones that begin to divide. When a cell is completely riddled with damaged mitochondria, it commits apoptosis. This is why we don't see a build up of mutations, but instead see that organs begin to wither away. The surviving healthy tissue is now under increased stress. This explains why aging diseases are due to mutations in the nuclear genes and is a good clue to why trying to cure them all one by one is futile. The diseases of aging simply add stress to tissues that are already under duress due to loss of cells that committed apoptosis because of worn out mitochondria. If the mitochondria were healthy and the tissue were not withering away, we would not succumb to the diseases of aging. The whole aging process could be delayed as it is in birds. So what is different about birds? Why do they live so long? Lane goes on to explain that birds have far less free radical leakage in their mitochondria. This problem sounds simple enough. Doesn't this mean that more antioxidants should solve the problem? Not so fast, says Lane. Free radicals are actually an important signal that helps regulate energy production. Therefore, if we wish to extend lifespan by reducing free radical leakage, then the chemical receptors that detect free radicals must be enhanced to be more sensitive so that these signals are not blotted out. This is why rats have such a short lifespan. having a more refined detection system is a big evolutionary feat and there has to be a payoff a lot bigger than just extended life. Birds do have a special need: powered flight. Lane also points out that while humans don't live nearly as long as birds, we are much better off than other similarly sized mammals. So that means humans must have recently been under strong selection for longer lifespans and probably already have more sensitive
free radical detection equipment than other mammals. Lane believes that we might find we could significantly increase lifespan by tweaking just a few genes.
So what special selection pressure have humans been under for longer lifespan? It could have been a feedback loop of caring for their elderly and selection for longer lifespan. Therefore, there would be selection for behavior where humans tend to care for those who cannot care for themselves. In my last post, I linked this kind of caring with a tendency to have compassion and care for all disabled including our children. See, I told you I'd tie it all together!
However, Lane goes on to explain that as mitochondria become damaged through mutation they are displaced by healthy ones that begin to divide. When a cell is completely riddled with damaged mitochondria, it commits apoptosis. This is why we don't see a build up of mutations, but instead see that organs begin to wither away. The surviving healthy tissue is now under increased stress. This explains why aging diseases are due to mutations in the nuclear genes and is a good clue to why trying to cure them all one by one is futile. The diseases of aging simply add stress to tissues that are already under duress due to loss of cells that committed apoptosis because of worn out mitochondria. If the mitochondria were healthy and the tissue were not withering away, we would not succumb to the diseases of aging. The whole aging process could be delayed as it is in birds. So what is different about birds? Why do they live so long? Lane goes on to explain that birds have far less free radical leakage in their mitochondria. This problem sounds simple enough. Doesn't this mean that more antioxidants should solve the problem? Not so fast, says Lane. Free radicals are actually an important signal that helps regulate energy production. Therefore, if we wish to extend lifespan by reducing free radical leakage, then the chemical receptors that detect free radicals must be enhanced to be more sensitive so that these signals are not blotted out. This is why rats have such a short lifespan. having a more refined detection system is a big evolutionary feat and there has to be a payoff a lot bigger than just extended life. Birds do have a special need: powered flight. Lane also points out that while humans don't live nearly as long as birds, we are much better off than other similarly sized mammals. So that means humans must have recently been under strong selection for longer lifespans and probably already have more sensitive
free radical detection equipment than other mammals. Lane believes that we might find we could significantly increase lifespan by tweaking just a few genes.
So what special selection pressure have humans been under for longer lifespan? It could have been a feedback loop of caring for their elderly and selection for longer lifespan. Therefore, there would be selection for behavior where humans tend to care for those who cannot care for themselves. In my last post, I linked this kind of caring with a tendency to have compassion and care for all disabled including our children. See, I told you I'd tie it all together!
Friday, January 29, 2010
Why do humans care for their disabled children?
I recently came across an article in Discover magazine that talks about the discovery a fossil a disabled child half million years old that was cared for and nurtured for 10 years. You can find the article here:
The fossil is 530,000 years old and belongs to the species Homo heidelbergensis. It is a 10 year old child with a birth defect that would have caused severe mental and physical handicaps. The fact that the child lived for 10 years is strong evidence that we developed the will and capacity to care for severely disabled offspring long before we became fully human. Such behavior of course is not evolutionarily adaptive. In fact, the effort that must have been exerted to care for this child who would no doubt have no chance of producing offspring of his own, would have had to be much greater than the effort required for the care of a child without such impairments. This effort must have extended to the tribe not just to the mother.
In evolutionary biology, a trait is adaptive if it is heritable and it bolsters reproductive success. The fact that caring for a disabled child is not adaptive means that it is truly a selfless act.
This article struck a personal note for me because I have a 9 year old little boy with severe mental and physical disabilities. How is it that my love for my children is equal when from an evolutionary perspective, one might assume that I should invest all of my resources into the child with the potential of passing on my genes? Am I just conforming to some cultural norm? Boyd and Richerson (see my paper on cultural evolution in my culture evolves post below) talk about an arms race between cultural and biological evolution. The capacity for culture on balance is adaptive and improves the individual's chances of survival and passing on their genes. However, every adaptive trait has some kind of a compromise involved because evolution cannot produce perfect solutions to problems. Culture is an extreme example of this. Our capacity for culture, allows us to escape the tyrannical demands of our selfish biological interests. Because of culture, we are not necessarily chained to the demands of reproduction and survival.
A cultural explanation may be part of what's going on but cannot be the whole answer. Clearly, 530,000 years ago there were no organized religions guilting this tribe into caring for their disabled members. In fact, the child was probably a burden to the rest of the tribe so it is doubtful that the parents would have been judged harshly for choosing to abandon the child. So, it seems to me that these parents did what they did purely out of love.
Even in many modern cultures, having a disabled child may be looked down upon as a shameful thing. This may compel some parents to abandon their child at an institution and keep the whole thing a secret. Nevertheless, there are many examples of parents raising their disabled children even when they are looked down upon and shamed by their culture (I need to do some research to get some clear examples of this.) So, cultural conformity is not the explanation. Despite being maladaptive I believe there is a strong biological tendency for parents to care for their disabled children. Parents that make these sacrifices do so out of love, and not necessarily because of cultural conformity.
If this is true, then how did such a tendency that transcends cultures escape the tyrannical hatchet of natural selection? I believe that the answer may be connected to the uniquely human trait of caring for our elderly. Such care is biologically adaptive. Tribal elders were a vast resource for vital knowledge in ancient societies. Tribes that cared for their elderly eventually out-competed those that didn't. We learned to have compassion for and to take care of those who could not care for themselves. Care for the elderly has clear biological advantages that have been selected for. Is it possible that the same cultural mechanisms that evolved to care for our elderly are the same ones that compel us to love our children unconditionally and to experience love in its purest form?
The fossil is 530,000 years old and belongs to the species Homo heidelbergensis. It is a 10 year old child with a birth defect that would have caused severe mental and physical handicaps. The fact that the child lived for 10 years is strong evidence that we developed the will and capacity to care for severely disabled offspring long before we became fully human. Such behavior of course is not evolutionarily adaptive. In fact, the effort that must have been exerted to care for this child who would no doubt have no chance of producing offspring of his own, would have had to be much greater than the effort required for the care of a child without such impairments. This effort must have extended to the tribe not just to the mother.
In evolutionary biology, a trait is adaptive if it is heritable and it bolsters reproductive success. The fact that caring for a disabled child is not adaptive means that it is truly a selfless act.
This article struck a personal note for me because I have a 9 year old little boy with severe mental and physical disabilities. How is it that my love for my children is equal when from an evolutionary perspective, one might assume that I should invest all of my resources into the child with the potential of passing on my genes? Am I just conforming to some cultural norm? Boyd and Richerson (see my paper on cultural evolution in my culture evolves post below) talk about an arms race between cultural and biological evolution. The capacity for culture on balance is adaptive and improves the individual's chances of survival and passing on their genes. However, every adaptive trait has some kind of a compromise involved because evolution cannot produce perfect solutions to problems. Culture is an extreme example of this. Our capacity for culture, allows us to escape the tyrannical demands of our selfish biological interests. Because of culture, we are not necessarily chained to the demands of reproduction and survival.
A cultural explanation may be part of what's going on but cannot be the whole answer. Clearly, 530,000 years ago there were no organized religions guilting this tribe into caring for their disabled members. In fact, the child was probably a burden to the rest of the tribe so it is doubtful that the parents would have been judged harshly for choosing to abandon the child. So, it seems to me that these parents did what they did purely out of love.
Even in many modern cultures, having a disabled child may be looked down upon as a shameful thing. This may compel some parents to abandon their child at an institution and keep the whole thing a secret. Nevertheless, there are many examples of parents raising their disabled children even when they are looked down upon and shamed by their culture (I need to do some research to get some clear examples of this.) So, cultural conformity is not the explanation. Despite being maladaptive I believe there is a strong biological tendency for parents to care for their disabled children. Parents that make these sacrifices do so out of love, and not necessarily because of cultural conformity.
If this is true, then how did such a tendency that transcends cultures escape the tyrannical hatchet of natural selection? I believe that the answer may be connected to the uniquely human trait of caring for our elderly. Such care is biologically adaptive. Tribal elders were a vast resource for vital knowledge in ancient societies. Tribes that cared for their elderly eventually out-competed those that didn't. We learned to have compassion for and to take care of those who could not care for themselves. Care for the elderly has clear biological advantages that have been selected for. Is it possible that the same cultural mechanisms that evolved to care for our elderly are the same ones that compel us to love our children unconditionally and to experience love in its purest form?
Tuesday, January 19, 2010
Bioinformatics and scientific workflows
This semester I am working with a fellow research student to develop some workflows to automate some analyses for my bioinformatics professor. This week I have been evaluating a scientific workflow solution called Taverna. I have been learning the basics from a powerpoint presentation here.
Taverna allows the user to construct workflows from pre-existing modules that do everything from retrieving sequences in genbank to aligning, analyzing and displaying the data in graph form. This is definitely a fully featured workflow solution. Workflows can be configured to be fail-safe, meaning I can specify alternate modules if 1 is not presently available. Also, when specifying more than 1 input, for example 4 gene sequences instead of 1, Taverna will automatically iterate over each input.
Our next task will be to discover if our workflow problem can be solved by configuring Taverna workflow with modules that already exist. I would actually like to use the API to create my own modules. Also, we need to investigate how easy it is take advantage of multiple processors and machines.
Taverna allows the user to construct workflows from pre-existing modules that do everything from retrieving sequences in genbank to aligning, analyzing and displaying the data in graph form. This is definitely a fully featured workflow solution. Workflows can be configured to be fail-safe, meaning I can specify alternate modules if 1 is not presently available. Also, when specifying more than 1 input, for example 4 gene sequences instead of 1, Taverna will automatically iterate over each input.
Our next task will be to discover if our workflow problem can be solved by configuring Taverna workflow with modules that already exist. I would actually like to use the API to create my own modules. Also, we need to investigate how easy it is take advantage of multiple processors and machines.
Thursday, January 14, 2010
Mitochondria and the meaning of life
I stated in my last post that it would be impossible for bacteria to evolve eukaryote-like complexity without symbiosis because trim genomes and small size are selected for. The size of bacteria is constrained because they need a high surface area to volume ratio in order to respire. But, some bacteria have found ways to increase surface area by changing shape or with infolded membranes. We know that this path has never led to complexity over 4 billion years of evolution, but why?
Lane believes that it is because as energy generation becomes larger and more complex, local control is essential. We all know that mitochondria have their own genome. Over time, mitochondrial genes have migrated to the nucleus. The exact genes that have migrated are different in different species but there is no species that has lost all mitochondrial genes. The ones that are retained generally benefit local energy production regulation. There are many disadvantages to retaining genes in the mitochondria. They evolve about 20 times faster than nuclear genes as they are more susceptible to mutation. Also, the genetic machinery must be maintained in each of the hundreds of mitochondria in each cell. Since we know that there is not even 1 example of a eukaryote losing all of its mitochondrial genes, there must be a huge advantage to these genetic outposts. Lane argues that local control is absolutely essential. If mitochondria didn't have their own genomes, they would not be able to individually regulate energy production. Regulating hundreds of mitochondria from the nucleus would be extremely complex and it may not be possible for such a mechanism to evolve. This is the problem with bacteria with infolded membranes. If they were to grow and become more complex, localized control of energy production would be essential but there is no mechanism for such a structure to evolve. Symbiosis got around this problem. That is why eukaryotes alone broke free of their bacterial chains!
Lane believes that it is because as energy generation becomes larger and more complex, local control is essential. We all know that mitochondria have their own genome. Over time, mitochondrial genes have migrated to the nucleus. The exact genes that have migrated are different in different species but there is no species that has lost all mitochondrial genes. The ones that are retained generally benefit local energy production regulation. There are many disadvantages to retaining genes in the mitochondria. They evolve about 20 times faster than nuclear genes as they are more susceptible to mutation. Also, the genetic machinery must be maintained in each of the hundreds of mitochondria in each cell. Since we know that there is not even 1 example of a eukaryote losing all of its mitochondrial genes, there must be a huge advantage to these genetic outposts. Lane argues that local control is absolutely essential. If mitochondria didn't have their own genomes, they would not be able to individually regulate energy production. Regulating hundreds of mitochondria from the nucleus would be extremely complex and it may not be possible for such a mechanism to evolve. This is the problem with bacteria with infolded membranes. If they were to grow and become more complex, localized control of energy production would be essential but there is no mechanism for such a structure to evolve. Symbiosis got around this problem. That is why eukaryotes alone broke free of their bacterial chains!
Wednesday, January 13, 2010
Why are bacteria eternally simple?
This question is explored in Nick Lane's book Power, Sex, Suicide. Eukaryotes are indeed unusual. They alone have ascended above the simple constraints of bacterial life.
Bacteria remain simple because natural selection keeps them simple. Unlike eukaryotes, most bacteria have no junk DNA at all. Copying the genome takes time. When bacteria are dividing, those that are fastest will quickly take over. Therefore, junk DNA is quickly discarded. Any gene that is not absolutely essential will be lost over time. Bacteria are very thrifty in this way and this keeps complexity in check and keeps their genome trim. Another constraint is size. Bacteria respire through their cell membrane. If a bacterium were to increase in size, it's surface area with respect to volume quickly plummets. This makes it hard to generate the energy that it needs. Therefore, it is not possible for bacteria to achieve the complexity of eukaryotes through the gradual Darwinian process of natural selection even over the billions of years they have existed. Bacteria remain eternally bacteria.
As I discussed in an earlier post, eukaryotes escaped these bonds through symbiosis. Our mitochondria freed us from a bacterial prison. With mitochondrial to power us, cells could get bigger increase in complexity.
So what is so special about mitochondria? Are bacteria really eternally doomed? Some bacteria have infolded cell walls to increase surface area, why couldn't this have gradually led to eukaryote-like complexity? I will tackle these questions and more next time!
Bacteria remain simple because natural selection keeps them simple. Unlike eukaryotes, most bacteria have no junk DNA at all. Copying the genome takes time. When bacteria are dividing, those that are fastest will quickly take over. Therefore, junk DNA is quickly discarded. Any gene that is not absolutely essential will be lost over time. Bacteria are very thrifty in this way and this keeps complexity in check and keeps their genome trim. Another constraint is size. Bacteria respire through their cell membrane. If a bacterium were to increase in size, it's surface area with respect to volume quickly plummets. This makes it hard to generate the energy that it needs. Therefore, it is not possible for bacteria to achieve the complexity of eukaryotes through the gradual Darwinian process of natural selection even over the billions of years they have existed. Bacteria remain eternally bacteria.
As I discussed in an earlier post, eukaryotes escaped these bonds through symbiosis. Our mitochondria freed us from a bacterial prison. With mitochondrial to power us, cells could get bigger increase in complexity.
So what is so special about mitochondria? Are bacteria really eternally doomed? Some bacteria have infolded cell walls to increase surface area, why couldn't this have gradually led to eukaryote-like complexity? I will tackle these questions and more next time!
Wednesday, January 6, 2010
Origin of the Eukaryotic cell. A truly unlikely event.
According to Nick Lane in his books Life Ascending and Power, Sex, Suicide, the origin of the eukaryotic cell was truly an unlikely event. If we could rewind the tape and try it again, chances are life would appear every time, but the appearance of eukaryotes was contingent on an unlikely chain of events. Because of this, Lane doubts that life more complex than bacteria exists beyond earth. After all, after billions of years it only appeared once on earth.
We now know that the first eukaryote was formed by the merger of 2 prokaryotes. The traditional idea of origins was that a primitive eukaryote engulfed the ancestor of our mitochondria since eukaryotes are known for phagocytosis, the abilty to engulf other cells. However, this is probably not how it happened because the ability to engulf other cells requires energy. It is now known that all eukaryotes either have mitochondria or have lost them at some point. Lane believes that this links the origin of eukaryotes with the acquisition of mitochondria. So, before the host cell acquired mitochondria, it wasn't going around engulfing other cells. Lane suggests that perhaps the 2 prokaryotes started out their symbiotic relationship by living in close proximity and progressed over time to a one cell living inside the other.
Genetic studies suggest that host cell was a methanogen archea. These cells are anaerobic meaning they survive on sulpher and stay away from oxygen. This seems unlikely because if this were true, why did eukaryotes appear just as oxygen levels were rising? As Lane points out, more oxygen means more sulphates because oxygen reacts with sulpher from volcanoes to produce sulphates. But, as we all know, most eukaryotes thrive in the presence of oxygen. Besides, what would use would a methenogen have for mitochondria which are useless without oxygen? Lane believes that the most likely answer is that the ancestor of mitochondria had a diverse genetic toolkit. Perhaps, it had the genes for utilizing hydrogen and oxygen. Once it started supplying the hydrogen for the methanogen, it would no longer be dependent on deep sea vents and could venture off into oxygenated environments. This primitive eukaryote would have had to adapt to the oxygenated environment before the mitochondria ancestor living inside it lost its oxygen utilizing genes through disuse.
This chain of events is just one way eukaryotes could have evolved. The lesson here is that there were enough contingencies that the ascent beyond bacteria only happened once on earth in the billions of years that bacteria have populated the earth. We are truly lucky to have made it through this bottleneck. The biggest gulf in all of life is the divide between prokaryotes and eukaryotes. We have more in common with a humble yeast cell than it does with a bacterium.
We now know that the first eukaryote was formed by the merger of 2 prokaryotes. The traditional idea of origins was that a primitive eukaryote engulfed the ancestor of our mitochondria since eukaryotes are known for phagocytosis, the abilty to engulf other cells. However, this is probably not how it happened because the ability to engulf other cells requires energy. It is now known that all eukaryotes either have mitochondria or have lost them at some point. Lane believes that this links the origin of eukaryotes with the acquisition of mitochondria. So, before the host cell acquired mitochondria, it wasn't going around engulfing other cells. Lane suggests that perhaps the 2 prokaryotes started out their symbiotic relationship by living in close proximity and progressed over time to a one cell living inside the other.
Genetic studies suggest that host cell was a methanogen archea. These cells are anaerobic meaning they survive on sulpher and stay away from oxygen. This seems unlikely because if this were true, why did eukaryotes appear just as oxygen levels were rising? As Lane points out, more oxygen means more sulphates because oxygen reacts with sulpher from volcanoes to produce sulphates. But, as we all know, most eukaryotes thrive in the presence of oxygen. Besides, what would use would a methenogen have for mitochondria which are useless without oxygen? Lane believes that the most likely answer is that the ancestor of mitochondria had a diverse genetic toolkit. Perhaps, it had the genes for utilizing hydrogen and oxygen. Once it started supplying the hydrogen for the methanogen, it would no longer be dependent on deep sea vents and could venture off into oxygenated environments. This primitive eukaryote would have had to adapt to the oxygenated environment before the mitochondria ancestor living inside it lost its oxygen utilizing genes through disuse.
This chain of events is just one way eukaryotes could have evolved. The lesson here is that there were enough contingencies that the ascent beyond bacteria only happened once on earth in the billions of years that bacteria have populated the earth. We are truly lucky to have made it through this bottleneck. The biggest gulf in all of life is the divide between prokaryotes and eukaryotes. We have more in common with a humble yeast cell than it does with a bacterium.
Sunday, January 3, 2010
Bioinformatics and vertebrate hox cluster evolution
Last semester, I took Molecular Evolution and Bioinformatics. It was such a blast! For my final project, I compared hox cluster sequences of humans and other vertebrates with the non vertebrate chordate Amphioxus or Lancelet. Most vertebrates have 4 hox clusters of 14 genes each. Amphioxus has just 1 cluster of 14 genes. It has been known for a while that in the vertebrate line the entire genome was duplicated twice which explains why most have 4 hox clusters. For the most part these genes are well conserved across all chordates. However, the posterior hox genes 10-14 are highly divergent. Therefore, it is not known for sure how many hox genes the ancestral chordate had. It could have had less than 14 and further duplications happened in each line after they diverged or the original chordate could have had 14. I focused on the Amphihox 13 gene to determine it if it was closer to other amphihox genes or to the human hox 13 gene. I conclude that it is most likely closer to the human hox 13 genes and therefore existed in the ancestral chordate.
My final paper is here and the presentation is here.
There is nothing earth shattering here. But, it could be interesting for anyone curious about what bioinformatics is all about.
Next semester, I will be working with my bioinformatics professor to automate bioinformatic analysis using scientific workflows. So, there will definitely be much more on this topic in the future.
My final paper is here and the presentation is here.
There is nothing earth shattering here. But, it could be interesting for anyone curious about what bioinformatics is all about.
Next semester, I will be working with my bioinformatics professor to automate bioinformatic analysis using scientific workflows. So, there will definitely be much more on this topic in the future.
Friday, January 1, 2010
Culture evolves
Last semester at UVU I took a biology and culture topics course. The intersection between culture and biology is a hot topic right now and I was completely enthralled. At the end of the semester, we each had to do a presentation and write a paper on any topic that incorporates biology and culture.
I decided to write a paper on cultural evolution. Specifically, does culture evolve and if so, does it progress in giant leaps or in small increments the way that biological evolution does. This is an interesting question and I was actually surprised by the answer. Logically, we might assume that cultural evolution progresses in giant leaps because unlike biological evolution, it is a guided process. However, the evidence I present in the paper says that the opposite is the case.
I read a lot for this project and referenced a lot of sources. The biggest and most important of these were the book Not By Genes Alone by Richerson and Boyd. I highly recommend this book for anyone who wants to understand how culture evolves. Some evolutionary thinkers such as Richard Dawkins have argued that culture evolves in a genelike way. He calls them "memes". Others such as Dan Sperber have argued that culumulative cultural evolution is not possible because culture is not faithfully transmitted like genes are. Culture is transmitted analogously. The way cultural traits are transmitted depend heavily on the idiosyncrasies of individuals. However, Richerson and Boyd argue that culture definitely does evolve but memelike transmission is not necessary. In fact, they say that a high mutation rate is actually necessary to prevent it from spiraling out of control!
You can download and read my complete paper here. There was a powerpoint presentation that went with it and you can get that here.
More on this topic later. Enjoy!
I decided to write a paper on cultural evolution. Specifically, does culture evolve and if so, does it progress in giant leaps or in small increments the way that biological evolution does. This is an interesting question and I was actually surprised by the answer. Logically, we might assume that cultural evolution progresses in giant leaps because unlike biological evolution, it is a guided process. However, the evidence I present in the paper says that the opposite is the case.
I read a lot for this project and referenced a lot of sources. The biggest and most important of these were the book Not By Genes Alone by Richerson and Boyd. I highly recommend this book for anyone who wants to understand how culture evolves. Some evolutionary thinkers such as Richard Dawkins have argued that culture evolves in a genelike way. He calls them "memes". Others such as Dan Sperber have argued that culumulative cultural evolution is not possible because culture is not faithfully transmitted like genes are. Culture is transmitted analogously. The way cultural traits are transmitted depend heavily on the idiosyncrasies of individuals. However, Richerson and Boyd argue that culture definitely does evolve but memelike transmission is not necessary. In fact, they say that a high mutation rate is actually necessary to prevent it from spiraling out of control!
You can download and read my complete paper here. There was a powerpoint presentation that went with it and you can get that here.
More on this topic later. Enjoy!
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