Inference of Evolutionary Forces Acting on Human Biological Pathways.
Bottom Line: 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.This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets.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.
Affiliation: CMPG, Institute of Ecology and Evolution, University of Berne, Switzerland Swiss Institute of Bioinformatics SIB, Lausanne, Switzerland Present address: Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain email@example.com firstname.lastname@example.org.Show MeSH
Mentions: Our 2DNS test has several advantages over classical methods such as the MDK test. First, we focus on the detection of selection in functional groups of genes instead of single genes. Not only is a biological pathway or gene network a more natural unit to test for selection, but by pooling genes belonging to the same gene set, we avoid the exclusion of many genes that have undefined N/S ratios. Second, our test allows one to detect different selective regimes, whereas classical tests are often designed to evidence only one type of selection, usually positive selection. As proposed in figure 3, we can infer which selective regime could have acted on an outlier gene set from its position in the PN/PS-DN/DS plane. Still, different selective processes can yield similar patterns leading to ambivalent interpretations. However, we see this as a problem of the underlying biology (different processes generate similar patterns) rather than of the 2DNS test per se. In these cases, one could inspect the function of the genes of a candidate pathway in more detail to gain insight on the type of selection that might have acted on the gene set.Fig. 3.—
Affiliation: CMPG, Institute of Ecology and Evolution, University of Berne, Switzerland Swiss Institute of Bioinformatics SIB, Lausanne, Switzerland Present address: Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain email@example.com firstname.lastname@example.org.