Civilisation has left its mark on our genes

[Nadvojvoda Janez Kranjski]

Civilisation has left its mark on our genes
22:00 19 December 2005
From New Scientist Print Edition
Bob Holmes

Darwin’s fingerprints can be found all over the human genome. A detailed look at human DNA has shown that a significant percentage of our genes have been shaped by natural selection in the past 50,000 years, probably in response to aspects of modern human culture such as the emergence of agriculture and the shift towards living in densely populated settlements.

One way to look for genes that have recently been changed by natural selection is to study mutations called single-nucleotide polymorphisms (SNPs) – single-letter differences in the genetic code. The trick is to look for pairs of SNPs that occur together more often than would be expected from the chance genetic reshuffling that inevitably happens down the generations.

Such correlations are known as linkage disequilibrium, and can occur when natural selection favours a particular variant of a gene, causing the SNPs nearby to be selected as well.

Robert Moyzis and his colleagues at the University of California, Irvine, US, searched for instances of linkage disequilibrium in a collection of 1.6 million SNPs scattered across all the human chromosomes. They then looked carefully at the instances they found to distinguish the consequences of natural selection from other phenomena, such as random inversions of chunks of DNA, which can disrupt normal genetic reshuffling.

This analysis suggested that around 1800 genes, or roughly 7% of the total in the human genome, have changed under the influence of natural selection within the past 50,000 years. A second analysis using a second SNP database gave similar results. That is roughly the same proportion of genes that were altered in maize when humans domesticated it from its wild ancestors.

“Domesticated” humans

Moyzis speculates that we may have similarly “domesticated” ourselves with the emergence of modern civilisation.

“One of the major things that has happened in the last 50,000 years is the development of culture,” he says. “By so radically and rapidly changing our environment through our culture, we’ve put new kinds of selection [pressures] on ourselves.”

Genes that aid protein metabolism – perhaps related to a change in diet with the dawn of agriculture – turn up unusually often in Moyzis’s list of recently selected genes. So do genes involved in resisting infections, which would be important in a species settling into more densely populated villages where diseases would spread more easily. Other selected genes include those involved in brain function, which could be important in the development of culture.

But the details of any such sweeping survey of the genome should be treated with caution, geneticists warn. Now that Moyzis has made a start on studying how the influence of modern human culture is written in our genes, other teams can see if similar results are produced by other analytical techniques, such as comparing human and chimp genomes.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0509691102)

http://www.newscientist.com/article.ns?id=dn8483

[Nadvojvoda Janez Kranjski]

The study:

Global landscape of recent inferred Darwinian selection for Homo sapiens

By using the 1.6 million single-nucleotide polymorphism (SNP) genotype data set from Perlegen Sciences [Hinds, D. A., Stuve, L. L., Nilsen, G. B., Halperin, E., Eskin, E., Ballinger, D. G., Frazer, K. A. & Cox, D. R. (2005) Science 307, 1072-1079], a probabilistic search for the landscape exhibited by positive Darwinian selection was conducted. By sorting each high-frequency allele by homozygosity, we search for the expected decay of adjacent SNP linkage disequilibrium (LD) at recently selected alleles, eliminating the need for inferring haplotype. We designate this approach the LD decay (LDD) test. By these criteria, 1.6% of Perlegen SNPs were found to exhibit the genetic architecture of selection. These results were confirmed on an independently generated data set of 1.0 million SNP genotypes (International Human Haplotype Map Phase I freeze). Simulation studies indicate that the LDD test, at the megabase scale used, effectively distinguishes selection from other causes of extensive LD, such as inversions, population bottlenecks, and admixture. The 1,800 genes identified by the LDD test were clustered according to Gene Ontology (GO) categories. Based on overrepresentation analysis, several predominant biological themes are common in these selected alleles, including host-pathogen interactions, reproduction, DNA metabolism/cell cycle, protein metabolism, and neuronal function.

Download PDF: http://www.pnas.org/cgi/reprint/0509691102v1.pdf