Friday, April 14, 2006

Positive selection on gene expression in the human brain

There has been a fair bit of recent research on the role of positive selection on the evolution of the human brain with the discovery that genes such as FOXP2, ASPM and Microcephalin had undergone rapid evolution on the lineage leading to humans.

A new piece is added to this picture with the publication of a new paper in Current Biology on the evolution of gene expression (1) rather than changes in protein sequence, although the two are not mutually exclusive.

This research compared the amount of linkage disequilibrium (LD) which is expected to be high around genes that have experienced recent positive selection with the amount of expression divergence in four tissues (brain, heart, kidney and liver). There was found to be a positive correlation between LD and genes expression divergence in the brain but no the other three tissues. This indicates that the divergence in gene expression is most likely partly due to positive selection rather than another factor like the relaxation of selective constraint. These results show once again that the human brain which is arguably on of our most unique characteristics is clearly the product of evolution.

Other results include:

"Interestingly, the top 5% of gene orthology groups with the highest expression divergence as well as the highest LD contain many genes involved in metabolism (Supplemental data). These genes, most noticeably the ones involved in electron transport and energy pathways, increased significantly in expression in the human versus the chimpanzee brain. It has been argued that amino acid changes in proteins involved in these pathways might have been positively selected for, due to changes in brain size and lifespan."

"Because we observe correlation between LD and expression changes at the level of functional groups rather than individual genes, some or many of the expression changes selected for in the human lineage may have occurred more than to 200,000 years ago. Consequently, our results do not show that all of the expression changes in brain observed in the human lineage can be explained by events within the last 200,000 years. However, a detectable proportion of these events is recent and potentially associated with the origin of modern humans prior to their spread out of Africa."

This seems to agree with other recent research that there has been alot of selection acting on many genes in the human genome 10,000–40,000 years ago (2) and more recently (3). This type of research has the potential to reveal alot about the genetic basis of humanness and proces of human evolution, although as always there is plenty more to discover.

Refs:
1) Positive selection on gene expression in the human brain
Philipp Khaitovich, Kun Tang, Henriette Franz, Janet Kelso, Ines Hellmann, Wolfgang Enard, Michael Lachmann, and Svante Pääbo. Current biology (in press)
(LINK) full text seems to be available for free at the moment


2) Wang ET, Kodama G, Baldi P, Moyzis RK.
Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):135-40. Epub 2005 Dec 21.
Global landscape of recent inferred Darwinian selection for Homo sapiens.
(LINK)

3) Voight BF, Kudaravalli S, Wen X, Pritchard JK.
PLoS Biol. 2006 Mar;4(3):e72. Epub 2006 Mar 7.
A map of recent positive selection in the human genome.
(LINK)

2 comments:

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kanzure said...

Nice post. Here are some notes on the gene composition of the human brain. Microcephalin et al. aren't the only players.

- Bryan