title: Ascertaining regions affected by GC-biased gene conversion through weak-to-strong mutational hotspots.
abstract: A major objective for evolutionary biology is to identify regions affected by positive selection. High dN/dS values for proteins and accelerated lineage-specific substitution rates for non-coding regions are considered classic signatures of positive selection. However, these could also be the result of non-adaptive phenomena, such as GC-biased gene conversion (gBGC), which favors the fixation of strong (C/G) over weak (A/T) nucleotides. Recent estimates indicate that gBGC affected up to 20% of regions with signatures of positive selection. Here we evaluate the impact of gBGC through its molecular signature of weak-to-strong mutational hotspots. We implemented specific modifications to the test proposed by Tang and Lewontin (1999) for identifying regions of differential variability and applied it to regions previously investigated for the influence of gBGC. While we found significant agreement with previous reports, our results suggest a smaller influence of gBGC than previously estimated, warranting further development of methods for its detection.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: vgotea@nih.gov.
authors.forename: Valer
authors.initials: V
authors.lastname: Gotea
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Elnitski
mesh_terms: D000465:Algorithms; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D003198:Computer Simulation; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D005785:Gene Conversion; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D059645:Mutation Rate; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics; D016415:Sequence Alignment
chemical_list: C495401:ADCYAP1 protein, human; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
keywords: GC-biased gene conversion (gBGC); Modified Tang–Lewontin test; Mutation hotspots; Positive selection; Weak-to-strong mutation bias
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