Last year, Katie Pollard and colleagues published a couple of papers in which they identified regions of the human genome that had recently undergone an acceleration in their rate of evolution and characterized the expression pattern of an RNA gene located in one of those regions. The RNA gene is expressed in the developing brain, which lead people to speculate that it played some important role in making humans smarter than chimps (my round-up and stab at speculation can be seen here). Their approach toward identifying those regions is quite simple, but the cause of accelerated evolution in those regions is unclear. Are they evolving rapidly because of natural selection fixing beneficial mutations, or is evolution sped up because of higher mutation rates?
Pollard and colleagues started by searching for sequences that are highly conserved (ie, have very few changes) amongst all mammals, excluding humans. They then searched within the highly conserved sequences for those with the fastest rates of evolution along the lineage leading to humans, after the divergence with chimpanzees (see here for a review of relative rate tests). They dubbed these rapidly evolving human sequences "human accelerated regions" (HARs). The fastest evolving HAR contained a sequence encoding an RNA that is expressed in the developing neocortex, but not translated into a protein. The authors also attempted to detect signatures of positive selection using polymorphism data (see here and here), but they did not find much evidence for adaptive evolution from either the publicly available SNP data or their own resequencing data.
In their interpretation of the results, Pollard et al suggest that it's unclear whether the HARs are rapidly evolving because of natural selection or higher rates of mutation in humans. But in an opinion piece published in Trends in Genetics, Nicolas Galtier and Laurent Duret argue that variation in mutation rate is a more likely explanation for many of the HARs. Their argument is based upon the types of changes that have occurred within HARs and their location in the genome.
One nice feature of Pollard et al's study is the fact that they exclude relaxed selective constraint as an explanation for accelerated evolution along the human lineage. They do so by comparing the rates of evolution of HARs against that of four-fold synonymous sites (third positions in codons which do not change the amino acid encoded by the codon), which are assumed to evolve neutrally. If the HARs evolved at a rate equivalent to that of the synonymous sites, then the accelerated evolution would most likely be the result of relaxed selective constraint along the human lineage. But the HARs evolve much faster than the neutral rate, suggesting that the changes along the human lineage were driven by natural selection.
The changes along the human lineage are also biased towards going from adenine (A) and thymine (T) to guanine (G) and cytosine (C). These types of changes are referred to as weak to strong because A and T are held together by two hydrogen bonds, while G and C are held together by three hydrogen bonds. Throughout the majority of a genome, weak to strong and strong to weak changes should occur at approximately equal frequencies. At recombination hotspots, however, weak to strong changes will dominate. That's because the recombination events are initiated by double strand breaks (DSBs) in DNA, which are then repaired by one of a few DSB repair pathways. If an individual is heterozygous for an A/T and a G/C nucleotide at a site near a DSB, one of the DSB repair pathways is known to preferentially replace the A/T with G/C during the repair event (known as biased gene conversion, or BGC).
That's the mechanism by which mutational bias would allow for accelerated evolution in one region of a genome but not another. This would not explain accelerated evolution along any particular lineage unless the recombination hotspots differed between species. And they do! Gil McVean and colleagues used polymorphism data to study recombination in the human genome (reviewed here). They found that recombination hotspots are ephemeral, changing often since the divergence of humans and chimps. If recombination hotspots have changed, and those hotspots induce weak to strong mutations, and HARs are biased for weak to strong mutations, it follows that HARs can be explained by mutational bias.
Galtier and Duret use that logic to argue that many of the HARs identified by Pollard et al evolved rapidly because of mutation bias, not natural selection. Pollard et al do acknowledge the possibility that BGC could be responsible for the HARs, but nowhere near as aggressively as Galtier and Duret. Not only do the HARs have an excess of weak to strong substitutions, they are also located near recombination hotspots, further supporting the mutation explanation. Additionally, if natural selection were responsible for the HARs, you would expect the signature of selection spread widely around the region under selection. BGC, on the other hand, will produce a much more localized signature, which is what Pollard et al observed.
If Galtier and Duret's hypothesis is correct, then these HARs represent an "Achilles' heel" of the genome -- essentially the opposite of the natural selection hypothesis. Rather than being shaped by natural selection, the HARs may be highly mutable regions which must be tolerated despite the fact that they occur in functional regions (remember, they are highly conserved amongst all mammals studied except for humans). If a recombination hotspot were to appear in a functional sequence (or a functional sequence were to migrate into a highly recombining region, like Fxy in mice), you would observe accelerated evolution in that region. Natural selection would need to be even stronger to maintain the function of that sequence, but many of those sequences would rapidly evolve despite being under strong selective constraint.
Galtier N and Duret L. 2007. Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution. Trends Genet 23: 273-277 doi:10.1016/j.tig.2007.03.011
Pollard KS, Salama SR, King B, Kern AD, Dreszer T, et al. 2006. Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2: e168 doi:10.1371/journal.pgen.0020168
Pollard KS, Salama SR, Lambert N, Lambot M-A, Coppens S, et al. 2006. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443: 167-172 doi:10.1038/nature05113
Spencer CCA, Deloukas P, Hunt S, Mullikin J, Myers S, et al. 2006. The influence of recombination on human genetic diversity. PloS Genet 2: e148 doi:10.1371/journal.pgen.0020148
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Evolution is a Myth!
Many people, when they can't provide evidence for their theory, adopt the strategy of falsehood. Such is the case with many of those who have fallen victim to the propaganda of renowned evolutionists.
If evolutionists want to end the arguments all they have to do is, get their brilliant heads together and assemble a 'simple' living cell. This should be possible, since they certainly have a very great amount of knowledge about what is inside the 'simple' cell.
After all, shouldn't all the combined Intelligence of all the worlds scientist be able the do what chance encounters with random chemicals, without a set of instructions, accomplished about 4 billion years ago,according to the evolutionists, having no intelligence at all available to help them along in their quest to become a living entity. Surely then the evolutionists scientists today should be able to make us a 'simple' cell.
If it weren't so pitiful it would be humorous, that intelligent people have swallowed the evolution mythology.
Beyond doubt, the main reason people believe in evolution is that sources they admire, say it is so. It would pay for these people to do a thorough examination of all the evidence CONTRARY to evolution that is readily available: Try answersingenesis.org. The evolutionists should honestly examine the SUPPOSED evidence 'FOR' evolution for THEMSELVES.
Build us a cell, from scratch, with the required raw material, that is with NO cell material, just the 'raw' stuff, and the argument is over. But if the scientists are unsuccessful, perhaps they should try Mother Earth's recipe, you know, the one they claim worked the first time about 4 billion years ago, so they say. All they need to do is to gather all the chemicals that we know are essential for life, pour them into a large clay pot and stir vigorously for a few billion years, and Walla, LIFE!
Oh, you don't believe the 'original' Mother Earth recipe will work? You are NOT alone, Neither do I, and MILLIONS of others!
Macro evolution does NOT happen.
Many people, when they can't provide evidence for their theory, adopt the strategy of falsehood. Such is the case with many of those who have fallen victim to the propaganda of renowned evolutionists.
If evolutionists want to end the arguments all they have to do is, get their brilliant heads together and assemble a 'simple' living cell. This should be possible, since they certainly have a very great amount of knowledge about what is inside the 'simple' cell.
After all, shouldn't all the combined Intelligence of all the worlds scientist be able the do what chance encounters with random chemicals, without a set of instructions, accomplished about 4 billion years ago,according to the evolutionists, having no intelligence at all available to help them along in their quest to become a living entity. Surely then the evolutionists scientists today should be able to make us a 'simple' cell.
If it weren't so pitiful it would be humorous, that intelligent people have swallowed the evolution mythology.
Beyond doubt, the main reason people believe in evolution is that sources they admire, say it is so. It would pay for these people to do a thorough examination of all the evidence CONTRARY to evolution that is readily available: Try answersingenesis.org. The evolutionists should honestly examine the SUPPOSED evidence 'FOR' evolution for THEMSELVES.
Build us a cell, from scratch, with the required raw material, that is with NO cell material, just the 'raw' stuff, and the argument is over. But if the scientists are unsuccessful, perhaps they should try Mother Earth's recipe, you know, the one they claim worked the first time about 4 billion years ago, so they say. All they need to do is to gather all the chemicals that we know are essential for life, pour them into a large clay pot and stir vigorously for a few billion years, and Walla, LIFE!
Oh, you don't believe the 'original' Mother Earth recipe will work? You are NOT alone, Neither do I, and MILLIONS of others!
Thanks for the insight, Mr James Collins.
I feel so stupid for devoting my life to something that is just sooooo wrong. Do I have egg on my face or what?*
*of course, by egg, I mean that God-designed yolky substance that magically turns into a perfectly designed chicken for me to eat. The way its legs are shaped--meaty on one end, slender on the other--it's like their little protein-popsicles. Way to go God, thanks for designing the chicken leg so perfectly, it's Christ-dili-icious!
I'd love to stay and post some more inane comments but I gotta go worship Jesus, vote Republican, oppress a few homosexuals, and then help my son with his science project. His teachers are so stupid, filling his head full of facts and trying to instill him to think independently. I'm going to change all that of course. For his science project, he's designing a project that shows how the yearn for scientific inquiry can be cured through prayer. Man-o-man will the world be better off without the ills of empiricism, cause-and-effect learning, and curiosity. Then I think I'll stop by the Planned Parenthood clinic and make a few 16 year girls cry. Nothing makes me feel better than yelling at troubled adolescent females. Afterall, it's their fault for visiting that abominable place. After that, I'll go to bible study and tell all my crucifix-junky friends how I did God's work great today. Then I'll donate some money to the 700 club and go bitch-slap my wife, like it says in that great book. I love myself because I am great and Jesus loves me and tells me the truth. I believe everything in the bible because it is true. I'm a super-duper smart Jesus-genius. I love America**
**except for gays, pregnant teenagers, public school teachers, democrats, academics, scientists, muslims, New Yorkers, Nation readers, vegetarians, and immigrants***.
***except for Pedro, that Mexican guy who cuts my lawn, he's okay I guess.
I'm not clear how the DSB repair mechanism you describe alters mutation rates. It's based on gene conversion at mismatches - and the mismatch is only present if the mutation has already occurred on the homologous chromosome. As far as I can see, while it changes which types of mutations are retained, it shouldn't affect the mutation rate itself. Wouldn't the excess weak-to-strong mutations preserved by the biased conversion be exactly counterbalanced by the number of strong-to-weak mutations which are preferentially eliminated by the biased conversion?
What do we know about how recombination hotspots arise? Why *are* these regions more prone to recombination?
Finally, it seems clear from the above that HARs are likely to be associated with recombination hotspots, because of the bias in mutation types. The question then is why there is also a functional bias in the genes found in HARs (immune system genes, testis genes and brain development genes). It seems scarcely plausible that recombination hotspots are somehow selectively directed to regions of the genome based on the functions of the genes in that region.
Galtier & Duret present BGC as a sort-of localized meiotic drive mechanism. So, technically, it's not mutation bias, but it leads to the rapid fixation of weak to strong mutations at recombination hot spots.