Adaptação, quem diria, tem papel importante na evolução humana

Adaptation Plays Significant Role In Human Evolution

ScienceDaily (Jan. 20, 2009) — For years researchers have puzzled over whether adaptation plays a major role in human evolution or whether most changes are due to neutral, random selection of genes and traits.

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Pervasive Hitchhiking at Coding and Regulatory Sites in Humans
James J. Cai1, J. Michael Macpherson1, Guy Sella2¶, Dmitri A. Petrov1¶*

1 Department of Biology, Stanford University, Stanford, California, United States of America, 2 Department of Evolution, Systematics, and Ecology, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel

Abstract

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald–Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying natural selection at functional sites should affect levels and patterns of polymorphism at linked nonfunctional sites. Here, we search for these effects by analyzing patterns of neutral polymorphism in humans in relation to the rates of recombination, functional density, and functional divergence with chimpanzees. We find that the levels of neutral polymorphism are lower in the regions of lower recombination and in the regions of higher functional density or divergence. These correlations persist after controlling for the variation in GC content, density of simple repeats, selective constraint, mutation rate, and depth of sequencing coverage. We argue that these results are most plausibly explained by the effects of natural selection at functional sites—either recurrent selective sweeps or background selection—on the levels of linked neutral polymorphism. Natural selection at both coding and regulatory sites appears to affect linked neutral polymorphism, reducing neutral polymorphism by 6% genome-wide and by 11% in the gene-rich half of the human genome. These findings suggest that the effects of natural selection at linked sites cannot be ignored in the study of neutral human polymorphism.

Author Summary

There is much reported evidence for positive selection at specific loci in the human genome. Additional papers based on comparisons between the genomes of humans and chimpanzees have also suggested that adaptive evolution may be quite common. At the same time, it has been surprisingly hard to find unambiguous evidence that either positive or negative (background) selection is affecting genome-wide patterns of variation at neutral sites. Here, we evaluate the prevalence of positive or background selection by using two genome-wide datasets of human polymorphism. We document that levels of neutral polymorphism are substantially lower in the regions of (i) higher density of genes and/or regulatory regions, (ii) higher protein or regulatory divergence, and (iii) lower recombination. These patterns are robust to a number of possible confounding factors and suggest that effects of selection at linked sites cannot be ignored in the study of the human genome.

Citation: Cai JJ, Macpherson JM, Sella G, Petrov DA (2009) Pervasive Hitchhiking at Coding and Regulatory Sites in Humans. PLoS Genet 5(1): e1000336.

doi:10.1371/journal.pgen.1000336

Editor: Gil McVean, University of Oxford, United Kingdom

Received: August 26, 2008; Accepted: December 11, 2008; Published: January 16, 2009

Copyright: © 2009 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research was supported by the grant from the National Institutes of Health (GM077368) and the National Science Foundation (0317171) to DAP and a Flegg Fellowship and by the Israel Science Foundation (grant no. 1435/07) to GS.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: dpetrov@stanford.edu

¶ These authors are joint senior authors on this work.

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