Natural selection on functional modules, a genome-wide analysis.

TitleNatural selection on functional modules, a genome-wide analysis.
Publication TypeJournal Article
Year of Publication2011
AuthorsSerra, F, Arbiza, L, Dopazo, J, Dopazo, H
JournalPLoS Comput Biol
Volume7
Issue3
Paginatione1001093
Date Published2011 Mar
ISSN1553-7358
KeywordsAnimals; Databases, Genetic; Drosophila; Genome, Insect; Genome-Wide Association Study; Genomics; Mammals; Phylogeny; Selection, Genetic; Sequence Analysis, DNA
Abstract

Classically, the functional consequences of natural selection over genomes have been analyzed as the compound effects of individual genes. The current paradigm for large-scale analysis of adaptation is based on the observed significant deviations of rates of individual genes from neutral evolutionary expectation. This approach, which assumed independence among genes, has not been able to identify biological functions significantly enriched in positively selected genes in individual species. Alternatively, pooling related species has enhanced the search for signatures of selection. However, grouping signatures does not allow testing for adaptive differences between species. Here we introduce the Gene-Set Selection Analysis (GSSA), a new genome-wide approach to test for evidences of natural selection on functional modules. GSSA is able to detect lineage specific evolutionary rate changes in a notable number of functional modules. For example, in nine mammal and Drosophilae genomes GSSA identifies hundreds of functional modules with significant associations to high and low rates of evolution. Many of the detected functional modules with high evolutionary rates have been previously identified as biological functions under positive selection. Notably, GSSA identifies conserved functional modules with many positively selected genes, which questions whether they are exclusively selected for fitting genomes to environmental changes. Our results agree with previous studies suggesting that adaptation requires positive selection, but not every mutation under positive selection contributes to the adaptive dynamical process of the evolution of species.

DOI10.1371/journal.pcbi.1001093
Alternate JournalPLoS Comput Biol
PubMed ID21390268
PubMed Central IDPMC3048381