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. 2009 Jun 5:1:114-8.
doi: 10.1093/gbe/evp012.

Estimates of positive Darwinian selection are inflated by errors in sequencing, annotation, and alignment

Adrian Schneider  1 , Alexander Souvorov, Niv Sabath, Giddy Landan, Gaston H Gonnet, Dan Graur
Affiliations

Estimates of positive Darwinian selection are inflated by errors in sequencing, annotation, and alignment

Adrian Schneider et al. Genome Biol Evol. .

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: gene annotation; multiple sequence alignment; positive Darwinian selection; sequencing quality.

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Figures

F<sc>IG</sc>. 1.—
FIG. 1.—
Unrooted scaled phylogenetic tree for seven eutherian species. The numbers on the branches are the mean numbers of nonsynonymous substitutions per nonsynonymous sites as inferred from the CODEML analysis. The percentages in parentheses above the downward pointing arrow next to the species name indicate inferred percentages of PSGs in the terminal branch leading from the immediate ancestor to the species when all genes are used. The percentages in parentheses below the downward pointing arrow indicate inferred percentages of PSGs when only all good genes are used. In human, in which a record of trace data has not been kept, all good indicates known annotation status and 100% HoT scores.
See this image and copyright information in PMC

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