title: Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System.
abstract: The ratio of nonsynonymous to synonymous substitution rates (ω) is often used to measure the strength of natural selection. However, ω may be influenced by linkage among different targets of selection, that is, Hill-Robertson interference (HRI), which reduces the efficacy of selection. Recombination modulates the extent of HRI but may also affect ω by means of GC-biased gene conversion (gBGC), a process leading to a preferential fixation of G:C ("strong," S) over A:T ("weak," W) alleles. As HRI and gBGC can have opposing effects on ω, it is essential to understand their relative impact to make proper inferences of ω. We used a model that separately estimated S-to-S, S-to-W, W-to-S, and W-to-W substitution rates in 8,423 avian genes in the Ficedula flycatcher lineage. We found that the W-to-S substitution rate was positively, and the S-to-W rate negatively, correlated with recombination rate, in accordance with gBGC but not predicted by HRI. The W-to-S rate further showed the strongest impact on both dN and dS. However, since the effects were stronger at 4-fold than at 0-fold degenerated sites, likely because the GC content of these sites is farther away from its equilibrium, ω slightly decreases with increasing recombination rate, which could falsely be interpreted as a consequence of HRI. We corroborated this hypothesis analytically and demonstrate that under particular conditions, ω can decrease with increasing recombination rate. Analyses of the site-frequency spectrum showed that W-to-S mutations were skewed toward high, and S-to-W mutations toward low, frequencies, consistent with a prevalent gBGC-driven fixation bias.
authors.affiliation: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Paulina
authors.initials: P
authors.lastname: Bolívar
authors.affiliation: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Carina F
authors.initials: CF
authors.lastname: Mugal
authors.affiliation: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nater
authors.affiliation: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden Hans.Ellegren@ebc.uu.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Ellegren
mesh_terms: D000818:Animals; D001482:Base Composition / Q000235:genetics*; D001717:Birds / Q000235:genetics*; D019143:Evolution, Molecular; D005785:Gene Conversion / Q000235:genetics*; D014644:Genetic Variation; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D012641:Selection, Genetic
keywords: Hill–Robertson interference; dN/dS; divergence; diversity; gBGC; rate of molecular evolution