02578nas a2200301   4500008004100000022001400041245006900055210006600124260001300190300001300203490000600216520167900222653001201901653002301913653001501936653001901951653003401970653001302004653001202017653001402029653002302043653002702066100002102093700002102114700002002135700002002155856010102175       2011                        eng d  a1553-735800aNatural selection on functional modules, a genome-wide analysis.0 aNatural selection on functional modules a genomewide analysis  c2011 Mar  ae10010930 v73 a<p>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.</p>10aAnimals10aDatabases, Genetic10aDrosophila10aGenome, Insect10aGenome-Wide Association Study10aGenomics10aMammals10aPhylogeny10aSelection, Genetic10aSequence Analysis, DNA1 aSerra, François1 aArbiza, Leonardo1 aDopazo, Joaquin1 aDopazo, Hernán  uhttps://www.clinbioinfosspa.es/content/natural-selection-functional-modules-genome-wide-analysis