The jumble of brain evolution
Sunday, January 7, 2007
The setting-University of Chicago. The players-Bruce Lahn and Chung-I Wu, both researchers on brain evolution. The issue-whether the brain genes are evolving at a faster rate in humans than other genes, and also than the same brain genes in other primate and rodent lineages. And both coming up with exactly the opposite results!!!
This has got the potential to be one of the most interesting debates in Biology!
It all started in 2004 with Bruce Lahn (the person in the photu), who right from birth wanted to work on the human brain, published a paper in Cell that had come to the above conclusions. No wonder
the news gripped the scientific community by storm. Nonetheless, the Lahn group identified a few genes which had a very high rate of adaptive evolution, and set to work upon it later. They further published back to back papers in 2005 in Science which said that particular haplotypes of two genes- ASPM and microcephalin-which have evolved out quite recently have spread in the human population all around the world due to selective (or adaptive) evolution. What selection pressure, obviously, they couldnt say.
These papers probably blasted the patience off of quite a few researchers, for immediately in 2006, there was a simulation that quite bluntly said Bruce was wrong. The authors said that the spread of these haplotypes could be very well explained by an Out-Of-Africa expansion of human population. Quite logical in saying so. (I had also thought of the same, then ;) ) But Bruce followed up the letter saying
"...The demographic models they adopt, however, strongly contradict a decade of empirical research on human demographic history and do not account for the critical features of the data on which our argument for selection was based...."
with no further counter-arguments or evidences. That was the end of it.
Now, Dr. Chung-I Wu from the same place as Bruce - UChicago - has come up with a PLoS paper in December 2006 that again quite bluntly goes to proclaim BRUCE WAS WRONG! He says this more bluntly than the earlier challengers.
Dr. Wu has taken a larger dataset and tried to beat Bruce at his own game. While the 2004 paper had considered only house-keeping genes as the reference genes for quantifying evolution, these guys took a whopping 12,000 + genes for their study. Instead of comparing with house-keeping genes, they compare the brain genes with the entire genome. Their conclusions are:
1) Brain-expressed genes are evolving at a lower rate than the rest of the genome
2) Even Brain-specific genes are evolving at a lower rate than the brain-expressed genes
3) Although primate genes are faster-evolving than rodent-genes this observation could be flawed as the evolutionary distance is quite large.
Now there have been no comments on this paper till now, and believe me, I am keeping a watch. However, I feel there is one primary difference between the two studies that needs more explanation. Th2 2004 paper considers ony house-keeping genes while this paper considers all genes, regardless of their nature. The problem is, it has been reported that tissue-specific genes in mammalian genomes have evolved faster than the housekeeping genes (again from Uchicago). Thats obvious. Someone else has reported that reproductive genes are evolving at a high rate. In such a scenario, considering all genes - regardless of whether they are tissue-specific or not specific - might bias the overall rate of evolution of the genome-wide set. If towards the higher side, the brain genes would anyways look puny!
On the other hand, Bruce gives a logical reason for considering 95 or so house-keeping genes only:
"...Given that housekeeping genes perform basic cellular functions that are likely conserved across different species, they should have evolved predominantly under constraint (and experiencing little positive selection). If housekeeping genes also show higher Ka/Ks in primates, then it would cast doubt on the interpretation that the elevated Ka/Ks of nervous system genes in primates is the consequence of positive selection......."
Whatever the reason, I am waiting for Bruce's formal reply to this one, if at all he wants to get public about it. Or he might just settle the matter in his Department itself??
This has got the potential to be one of the most interesting debates in Biology!
It all started in 2004 with Bruce Lahn (the person in the photu), who right from birth wanted to work on the human brain, published a paper in Cell that had come to the above conclusions. No wonder
the news gripped the scientific community by storm. Nonetheless, the Lahn group identified a few genes which had a very high rate of adaptive evolution, and set to work upon it later. They further published back to back papers in 2005 in Science which said that particular haplotypes of two genes- ASPM and microcephalin-which have evolved out quite recently have spread in the human population all around the world due to selective (or adaptive) evolution. What selection pressure, obviously, they couldnt say.These papers probably blasted the patience off of quite a few researchers, for immediately in 2006, there was a simulation that quite bluntly said Bruce was wrong. The authors said that the spread of these haplotypes could be very well explained by an Out-Of-Africa expansion of human population. Quite logical in saying so. (I had also thought of the same, then ;) ) But Bruce followed up the letter saying
"...The demographic models they adopt, however, strongly contradict a decade of empirical research on human demographic history and do not account for the critical features of the data on which our argument for selection was based...."
with no further counter-arguments or evidences. That was the end of it.
Now, Dr. Chung-I Wu from the same place as Bruce - UChicago - has come up with a PLoS paper in December 2006 that again quite bluntly goes to proclaim BRUCE WAS WRONG! He says this more bluntly than the earlier challengers.
Dr. Wu has taken a larger dataset and tried to beat Bruce at his own game. While the 2004 paper had considered only house-keeping genes as the reference genes for quantifying evolution, these guys took a whopping 12,000 + genes for their study. Instead of comparing with house-keeping genes, they compare the brain genes with the entire genome. Their conclusions are:
1) Brain-expressed genes are evolving at a lower rate than the rest of the genome
2) Even Brain-specific genes are evolving at a lower rate than the brain-expressed genes
3) Although primate genes are faster-evolving than rodent-genes this observation could be flawed as the evolutionary distance is quite large.
Now there have been no comments on this paper till now, and believe me, I am keeping a watch. However, I feel there is one primary difference between the two studies that needs more explanation. Th2 2004 paper considers ony house-keeping genes while this paper considers all genes, regardless of their nature. The problem is, it has been reported that tissue-specific genes in mammalian genomes have evolved faster than the housekeeping genes (again from Uchicago). Thats obvious. Someone else has reported that reproductive genes are evolving at a high rate. In such a scenario, considering all genes - regardless of whether they are tissue-specific or not specific - might bias the overall rate of evolution of the genome-wide set. If towards the higher side, the brain genes would anyways look puny!
On the other hand, Bruce gives a logical reason for considering 95 or so house-keeping genes only:
"...Given that housekeeping genes perform basic cellular functions that are likely conserved across different species, they should have evolved predominantly under constraint (and experiencing little positive selection). If housekeeping genes also show higher Ka/Ks in primates, then it would cast doubt on the interpretation that the elevated Ka/Ks of nervous system genes in primates is the consequence of positive selection......."
Whatever the reason, I am waiting for Bruce's formal reply to this one, if at all he wants to get public about it. Or he might just settle the matter in his Department itself??
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