The dynamics of “silent” variation in Mimulus guttatus : Codon usage bias and linked selection

Synonymous nucleotide variation, which is remarkably high in Mimulus guttatus , can be affected by both codon usage selection (translational efficiency) and linked selection (hitchhiking effects).

Codon usage reflects a genome-wide tug-of-war between mutational pressure toward A/T-ending codons and weak selection favoring G/C-ending codons. The outcome is determined largely by gene expression level and localized variation in recombination rate.

Using both mechanistic (ROC-SEMPPR) and population genetic models, we find that most genes are weakly selected for codon usage, about 76% yielding scaled selection coefficients (S = 4N _e s) in the range of 0 to 1. Additionally, 4029 genes, primarily involved in photosynthesis, translation, defense, and phosphate scavenging, experience strong selection (S > 1).

Levels of nucleotide variation within genes indicate a strong effect of linked selection. Non-synonymous polymorphism declines in genes with strong purifying selection, and as the rate of (intra-genic) recombination declines. Levels of synonymous polymorphism usually track non-synonymous (owing to background selection), except in genes under the strongest translational selection.

Counterintuitively, we find that codon usage selection has a generally positive effect on synonymous nucleotide diversity at 4-fold degenerate positions. Since mutation strongly disfavors the optimal base in M. guttatus , codon selection in the range of 0 < S < 2 evens the balance (between selection and mutation) and thus inflates heterozygosity.