Inference of Evolutionary Forces Acting on Human Biological Pathways.

Details

Ressource 1Download: BIB_F1C43009CD42.P001.pdf (3686.62 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_F1C43009CD42
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inference of Evolutionary Forces Acting on Human Biological Pathways.
Journal
Genome Biology and Evolution
Author(s)
Daub J.T., Dupanloup I., Robinson-Rechavi M., Excoffier L.
ISSN
1759-6653 (Electronic)
ISSN-L
1759-6653
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
7
Number
6
Pages
1546-1558
Language
english
Abstract
Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald-Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.
Keywords
McDonald-Kreitman test, human evolution, pathway analysis, polygenic selection
Pubmed
Web of science
Open Access
Yes
Create date
09/05/2015 15:05
Last modification date
20/08/2019 16:19
Usage data