PT  - JOURNAL ARTICLE
AU  - Heather E. Machado
AU  - David S. Lawrie
AU  - Dmitri A. Petrov
TI  - Strong selection at the level of codon usage bias: evidence against the Li-Bulmer model
AID  - 10.1101/106476
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 106476
4099  - http://biorxiv.org/content/early/2017/02/09/106476.short
4100  - http://biorxiv.org/content/early/2017/02/09/106476.full
AB  - Codon usage bias (CUB), where certain codons are used more frequently than expected by chance, is a ubiquitous phenomenon and occurs across the tree of life. The dominant paradigm is that the proportion of preferred codons is set by weak selection. While experimental changes in codon usage have at times shown large phenotypic effects in contrast to this paradigm, genome-wide population genetic estimates have supported the weak selection model. Here we use deep genomic sequencing of two Drosophila melanogaster populations to measure selection on synonymous sites in a way that allowed us to estimate the prevalence of both weak and strong selection. We find that selection in favor of preferred codons ranges from weak (|Nes| ∼ 1) to strong (|Nes| > 10). While previous studies indicated that selection at synonymous sites could be strong, this is the first study to detect and quantify strong selection specifically at the level of CUB. We suggest that the level of CUB in the genome is determined by the proportion of synonymous sites under no, weak, and strong selection. This model challenges the standard Li-Bulmer model and explains some of the longest-standing puzzles in the field.