Gene-Wide Identification of Episodic Selection

Abstract

We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than the synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring an a priori hypothesis regarding which branches are under positive selection) or on a pre-specified subset of foreground lineages (if a suitable a priori hypothesis is available). Selection is modeled as varying stochastically over branches and sites, and we propose a computationally inexpensive evidence metric for identifying sites subject to episodic positive selection on any foreground branches. We compare BUSTED with existing models on simulated and empirical data. An implementation is available on www.datamonkey.org/busted, with a widget allowing the interactive specification of foreground branches.

Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis

“…Because statistical measures of metapopulation structure can be affected by selection as well as migration dynamics, an unrestricted branch site random-effects model, referred to as BUSTED (Branch-Site Unrestricted Statistical Test for Episodic Diversification; implemented in the datamonkey webserver http://datamonkey.org), was used to test for gene-wide episodic diversifying selection (47). The analysis was restricted to only internal branches, which are assumed to capture at least one round of virus replication, to mitigate the biasing effects of transient deleterious mutations on the ratio of nonsynonymous to synonymous substitution rates estimates along terminal branches, where selection has not had time to fully filter such population level variation (48,49).…”

Insights into the Impact of CD8+Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression

“…Because statistical measures of metapopulation structure can be affected by selection as well as migration dynamics, an unrestricted branch-site random effects model, referred to as BUSTED (branch-site unrestricted statistical test for episodic diversification) (https://datamonkey.org), was used to test for gene-wide episodic diversifying selection (80). The analysis was restricted to internal branches, which are assumed to capture at least one round of virus replication, to mitigate the biasing effects of transient deleterious mutations on the ratio of nonsynonymous to synonymous substitution rate estimates along terminal branches, where selection has not had time to fully filter such populationlevel variation (81,82).…”

Evidence of neofunctionalization after the duplication of the highly conserved Polycomb group gene Caf1-55 in the obscura group of Drosophila

“…S3) in Caf1-55dup after its origin by duplication. Most of these codons also show a rather high evidence ratio of having been the target of positive selection according to BUSTED24.…”