Abstract for presentation at 11th International Congress of Human Genetics

Darwin’s Fingerprint: Accelerated recent adaptive evolution in humans

  • Eric Wang, 1Department of Biological Chemistry, University of California, Irvine College of Medicine. Irvine, CA 92697, United States
  • Pierre Baldi, 2School of Information and Computer Science, University of California, Irvine. Irvine, CA 92697, 3Institute of Genomics and Bio, United States
  • Robert Moyzis, 1Department of Biological Chemistry, University of California, Irvine College of Medicine. Irvine, CA 92697, United States
  • Dr Resie Vervenne, Dept. of Clinical Genetics, VU medical center, Amsterdam, The Netherlands
  • Dr Gerard Pals, Dept. of Clinical Genetics, VU medical center, Amsterdam, The Netherlands

    • Using the > 3.9 million single-nucleotide polymorphism (SNP) genotype datasets from Perlegen Sciences (Hinds et al., Science 307, 1072-1079, 2005), and the updated International Human HapMap Project (Nature 437, 1299-1320, 2005), 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 (Wang et al., PNAS 103, 135-140, 2006). The method relies only on high-heterozygousity SNPs for analysis, and is therefore applicable to the high ascertainment bias Perlegen and HapMap data sets. Using this sensitive LDD test, the fingerprint of recent inferred selection was uncovered for over 100 times more loci (> 5,000) than other published global approaches using less sensitive tests. Even with this increased sensitivity, simulation studies indicate that the LDD test, at the Mb scale employed, effectively distinguishes selection from other causes of extensive LD, such as inversions, population bottlenecks and admixture. The genes identified by the LDD test were clustered according to Gene-Ontology (GO) categories. Based on over-representation 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. While the number of selected alleles identified is large, it is similar to the estimated number obtained for artificial selection (by humans) on the maize genome (Wright et al., Science 308, 1310-1314, 2005). We have calculated allele ages for all selected sites, indicating that most of the human selective events occurred in the last 10,000-40,000 years, a time of major population expansion out of Africa followed by regional shifts from hunter-gatherer to agrarian societies. The acceleration of these adaptive events in recent evolutionary time suggests that gene-culture interactions directly or indirectly shaped the human genome.

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