Abstract
Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.
Highlights
Codon usage bias (CUB), where synonymous codons are not used in equal frequencies, is well documented across species from all three domains of life (Duret 2002; Chen et al 2004)
Results GC-biased gene conversion (gBGC) Has Little Impact on GC Composition in D. discoideum In mammals, local biased gene conversion hotspots can cause codon usage bias (CUB) to vary across the genome and reflect the local composition in the genomic region where it is found (D’Onofrio et al 1991; Urrutia and Hurst 2001)
GC content is largely evenly distributed across all chromosomes apart from a few peaks that are associated with genomic regions enriched in transposable elements
Summary
Codon usage bias (CUB), where synonymous codons are not used in equal frequencies, is well documented across species from all three domains of life (Duret 2002; Chen et al 2004). A purely neutral framework has been proposed in which CUB arises as a consequence of mutational bias (Kimura 1968; King and Jukes 1969; Sueoka 1988; Palidwor et al 2010) This framework can explain a large proportion of variation in CUB across taxa, including bacteria, archaea, plants, and animals, where mutational bias has presumably shaped GC% at third codon positions (GC3) to vary from near zero to nearly 100% across species (Knight et al 2001; Palidwor et al 2010).
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