Inference of Evolutionary Forces Acting on Human Biological Pathways.

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_F1C43009CD42
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inference of Evolutionary Forces Acting on Human Biological Pathways.
Périodique
Genome Biology and Evolution
Auteur(s)
Daub J.T., Dupanloup I., Robinson-Rechavi M., Excoffier L.
ISSN
1759-6653 (Electronic)
ISSN-L
1759-6653
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
7
Numéro
6
Pages
1546-1558
Langue
anglais
Résumé
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.
Mots-clé
McDonald-Kreitman test, human evolution, pathway analysis, polygenic selection
Pubmed
Web of science
Création de la notice
09/05/2015 16:05
Dernière modification de la notice
03/03/2018 22:39
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