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Genome Biology and Evolution Advance Access originally published online on June 5, 2009
Genome Biology and Evolution (2009) Vol. 2009:114; doi:10.1093/gbe/evp012 published on June 22, 2009
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Estimates of Positive Darwinian Selection Are Inflated by Errors in Sequencing, Annotation, and Alignment

Adrian Schneider*, Alexander Souvorov{dagger}, Niv Sabath{ddagger}, Giddy Landan{ddagger}, Gaston H. Gonnet* and Dan Graur{ddagger}

* ETH Zürich, Zürich, Switzerland
{dagger} National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland
{ddagger} Department of Biology and Biochemistry, University of Houston

E-mail: dgraur{at}uh.edu.


  Abstract

Published estimates of the proportion of positively selected genes (PSGs) in human vary over three orders of magnitude. In mammals, estimates of the proportion of PSGs cover an even wider range of values. We used 2,980 orthologous protein-coding genes from human, chimpanzee, macaque, dog, cow, rat, and mouse as well as an established phylogenetic topology to infer the fraction of PSGs in all seven terminal branches. The inferred fraction of PSGs ranged from 0.9% in human through 17.5% in macaque to 23.3% in dog. We found three factors that influence the fraction of genes that exhibit telltale signs of positive selection: the quality of the sequence, the degree of misannotation, and ambiguities in the multiple sequence alignment. The inferred fraction of PSGs in sequences that are deficient in all three criteria of coverage, annotation, and alignment is 7.2 times higher than that in genes with high trace sequencing coverage, "known" annotation status, and perfect alignment scores. We conclude that some estimates on the prevalence of positive Darwinian selection in the literature may be inflated and should be treated with caution.

Keywords: multiple sequence alignment, sequencing quality, gene annotation, positive Darwinian selection

Accepted May 21, 2009

William Martin, Associate Editor


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