March 05, 2008

Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

This is an open access article, so you can read it all for yourselves; the main conclusion is easy enough to grasp:
  • Genes related to metabolic disorders influence the body's energy management
  • Energy management is crucial for adapting to different climates, e.g., managing cold (example the higher basal metabolic rate of the Siberian Yakut).
  • It is expected theoretically that such genes would have been subjected to natural selection as humans spread around the world and found themselves in different climates
Indeed, this theoretical prediction is supported by the data. What this means, practically, is that for many genes involved in metabolism, similarity of climate implies to some extent similar allele distributions, due to similar selective pressures; spatial proximity or population history do not suffice. Indeed, Natural selection has driven population differentiation in modern humans.

It is noteworthy how much research into the evolution of humans has been based on the 52 populations of the Human Genome Diversity Project. It is precisely by looking at how human populations differ from each other genetically, and correlating this with their different environments and cultures that we will be able to derive a more complete history of our species.

(Yann also blogged about this)

PLoS Genetics

Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

Angela M. Hancock et al.

Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.



Daniel said...

For what it's worth, I've got an excessively long post on this article here:

It's an elegant study, and I'll be posting more about it over the next month or so.

Daniel said...

Whoops - for my post, click here.