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PMID: 19411606 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The difficulty of avoiding false positives in genome scans for natural selection.

Genome research ·Vol. 19 ·No. 5 ·2009-05-00 ·Pages 922-33

Mallick S, Gnerre S, Muller P, Reich D

Abstract

Several studies have found evidence for more positive selection on the chimpanzee lineage compared with the human lineage since the two species split. A potential concern, however, is that these findings may simply reflect artifacts of the data: inaccuracies in the underlying chimpanzee genome sequence, which is of lower quality than human. To test this hypothesis, we generated de novo genome assemblies of chimpanzee and macaque and aligned them with human. We also implemented a novel bioinformatic procedure for producing alignments of closely related species that uses synteny information to remove misassembled and misaligned regions, and sequence quality scores to remove nucleotides that are less reliable. We applied this procedure to re-examine 59 genes recently identified as candidates for positive selection in chimpanzees. The great majority of these signals disappear after application of our new bioinformatic procedure. We also carried out laboratory-based resequencing of 10 of the regions in multiple chimpanzees and humans, and found that our alignments were correct wherever there was a conflict with the published results. These findings throw into question previous findings that there has been more positive selection in chimpanzees than in humans since the two species diverged. Our study also highlights the challenges of searching the extreme tails of distributions for signals of natural selection. Inaccuracies in the genome sequence at even a tiny fraction of genes can produce false-positive signals, which make it difficult to identify loci that have genuinely been targets of selection.

MeSH Terms
Animals Base Sequence Evolution, Molecular Genome Genomics Humans Molecular Sequence Data Pan troglodytes/genetics Selection, Genetic Sequence Alignment Sequence Analysis, DNA Synteny
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mallick Swapan
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. [email protected]
Gnerre Sante
Muller Paul
Reich David
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.086512.108
Email
[email protected]
Published
2009-05-00
Pages
922-33
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC2675981
Subset
IM
Grants
NHGRI NIH HHS · U01 HG004168 · United States
NHGRI NIH HHS · U01 HG 004168 · United States
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External Links
PubMed source DOI: 10.1101/gr.086512.108 PMC Full Text View journal details
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