An Empirical Test for Branch-Specific Positive Selection

Abstract

The use of phylogenetic analysis to predict positive selection specific to human genes is complicated by the very close evolutionary relationship with our nearest extant primate relatives, chimpanzees. To assess the power and limitations inherent in use of maximum-likelihood (ML) analysis of codon substitution patterns in such recently diverged species, a series of simulations was performed to assess the impact of several parameters of the evolutionary model on prediction of human-specific positive selection, including branch length and d N /d S ratio. Parameters were varied across a range of values observed in alignments of 175 transcription factor (TF) genes that were sequenced in 12 primate species. The ML method largely lacks the power to detect positive selection that has occurred since the most recent common ancestor between humans and chimpanzees. An alternative null model was developed on the basis of gene-specific evaluation of the empirical distribution of ML results, using simulated neutrally evolving sequences. This empirical test provides greater sensitivity to detect lineage-specific positive selection in the context of recent evolutionary divergence.

Evidence for positive selection in the gene fruitless in Anastrephafruit flies

“…Both dN/dS and MM01 analyses require that the differences among sequences represent fixed substitutions among very well defined lineages [ 29 , 45 , 46 ]. When dealing with data from recently diverged lineages, few fixed substitution are found among sequences, and consequently, the power of the tests to discriminate between positive and purifying selection is reduced [ 47 ]. Additionally, recently diverged lineages, such as the species A. fraterculus , A. sororcula and A. obliqua here considered, may still segregate ancestral polymorphisms.…”

Comparative genomics and the study of evolution by natural selection

“…Positive Darwin selection can be demonstrated for many genes and, again, selection seems more prevalent in larger populations. Since the ability to detect selection in DNA sequence data will in many cases be a matter of obtaining sufficient power (Nickel et al . 2008), it is likely that future work will strengthen the evidence for genic selection (Hahn 2008).…”

“…Positive Darwin selection can be demonstrated for many genes and, again, selection seems more prevalent in larger populations. Since the ability to detect selection in DNA sequence data will in many cases be a matter of obtaining sufficient power (Nickel et al 2008), it is likely that future work will strengthen the evidence for genic selection (Hahn 2008). However, at present, the old neutralistselectionist debate seems to have no clear winner; both drift and selection play important roles in molecular evolution and an outstanding challenge for future research will therefore be to reveal to what extent phenotypic evolution can be attributed to nonselective processes.…”

Alcohol impairs J774.16 macrophage-like cell antimicrobial functions inAcinetobacter baumanniiinfection

“…6 Moreover, EtOH exposure elevated serum IgG and IgA antibody levels indicative of B-cell dysfunction. 7 Macrophages play an important role in early modulation of immune response to multidrug-resistant Ab infection. 8 However, there is lack of information about EtOH abuse effects on specific effector functions of host cells in Ab infection.…”