Abstract
Molecular evolution is being revolutionized by high-throughput sequencing allowing an increased amount of genome-wide data available for multiple species. While base composition summarized by GC-content is one of the first metrics measured in genomes, its genomic distribution is a frequently neglected feature in downstream analyses based on DNA sequence comparisons. Here, we show how base composition heterogeneity among loci and taxa can bias common molecular evolution analyses such as phylogenetic tree reconstruction, detection of natural selection and estimation of codon usage. We then discuss the biological, technical and methodological causes of these GC-associated biases and suggest approaches to overcome them.
Highlights
GC-content is shaped by a complex balance among mutation, selection, recombination, and genetic drift (Bulmer, 1991; Eyre-Walker and Hurst, 2001; Duret et al, 2002)
Average GC-content of an alignment correlates strongly with GC-heterogeneity among sequences as a result of variation in the dynamic of GC-biased gene conversion (gBGC) among sampled species (Romiguier et al, 2013a). Such departures from the assumption of base composition homogeneity can lead to severe biases by incorrectly grouping distantly related taxa that converge in extreme nucleotide composition on a given locus (Phillips et al, 2004)
Initially challenged (Williamson et al, 2005), natural selection acting on standing synonymous variation was found to be associated to gene expression level, the most expressed genes using a set of preferred codons (Comeron, 2004)
Summary
GC-content is shaped by a complex balance among mutation, selection, recombination, and genetic drift (Bulmer, 1991; Eyre-Walker and Hurst, 2001; Duret et al, 2002). After several years of debate among neutral or selective hypotheses [reviewed in Duret and Galtier (2009)], it is widely accepted that one of the major drivers of base composition heterogeneity is GC-biased gene conversion (gBGC), a repair bias that favors GC over AT alleles during meiotic recombination (Eyre-Walker, 1993; Galtier et al, 2001; Montoya-Burgos et al, 2003; Duret and Arndt, 2008; Kent et al, 2012; Arbeithuber et al, 2015; Mugal et al, 2015). We revisit how much intra-genomic and inter-specific variations in base composition have a strong power to bias popular analyses in molecular evolution such as phylogenetic tree reconstruction, detection of natural selection and estimation of codon usage bias (Figure 1)
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