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Genome Biology and Evolution Advance Access published online on June 5, 2009
Genome Biology and Evolution, doi:10.1093/gbe/evp012
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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 Schneider1, Alexander Souvorov2, Niv Sabath3, Giddy Landan3, Gaston H. Gonnet1 and Dan Graur3,4

1 ETH Zürich, CH-8092 Zürich, Switzerland (adrian.schneider{at}inf.ethz.ch; gonnet{at}inf.ethz.ch)
2 National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA (souvorov{at}ncbi.nlm.nih.gov)
3 Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001, USA (nsabath{at}uh.edu; giddy.landan{at}gmail.com; dgraur{at}uh.edu)

4 Correspondence to dgraur{at}uh.edu


  Abstract

Published estimates of the proportion of positively selected genes in human vary over three orders of magnitude. In mammals, estimates of the proportion of positively selected genes 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 positively selected genes in all seven terminal branches. The inferred fraction of positively selected genes 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 tell-tale signs of positive selection: the quality of the sequence, the degree of mis-annotation, and ambiguities in the multiple sequence alignment. The inferred fraction of positively selected genes 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

Received February 7, 2009; Revised May 14, 2009; Accepted May 21, 2009


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