PT  - JOURNAL ARTICLE
AU  - Zhen Peng
AU  - Hani Zaher
AU  - Yehuda Ben-Shahar
TI  - Natural selection on gene-specific codon usage bias is common across eukaryotes
AID  - 10.1101/292938
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 292938
4099  - http://biorxiv.org/content/early/2018/05/03/292938.short
4100  - http://biorxiv.org/content/early/2018/05/03/292938.full
AB  - Although the actual molecular evolutionary forces that shape differences in codon usage across species remain poorly understood, majority of synonymous mutations are assumed to be functionally neutral because they do not affect protein sequences. However, empirical studies suggest that some synonymous mutations can have phenotypic consequences. Here we show that in contrast to the current dogma, natural selection on gene-specific codon usage bias is common across Eukaryota. Furthermore, by using bioinformatic and experimental approaches, we demonstrate that specific combinations of rare codons contribute to the spatial and sex-related regulation of some protein-coding genes in Drosophila melanogaster. Together, these data indicate that natural selection can shape gene-specific codon usage bias, which therefore, represents an overlooked genomic feature that is likely to play an important role in the spatial and temporal regulation of gene functions. Hence, the broadly accepted dogma that synonymous mutations are in general functionally neutral should be reconsidered.