TY - JOUR T1 - Natural selection on gene-specific codon usage bias is common across eukaryotes JF - bioRxiv DO - 10.1101/292938 SP - 292938 AU - Zhen Peng AU - Hani Zaher AU - Yehuda Ben-Shahar Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/31/292938.abstract N2 - Genomic data from diverse taxa indicate that synonymous codon usage frequencies are often not random. Although the molecular evolutionary forces that shape codon usage remain poorly understood, synonymous mutations are generally assumed to be neutral because they do not affect protein sequences. However, empirical evidence indicates 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 spatial and sex-related regulation of protein expression in Drosophila melanogaster. These data indicate that natural selection shapes gene-specific codon usage biases, and therefore, it represents an overlooked genomic feature that plays an important role in the spatial and temporal regulation of gene functions. Hence, the broadly accepted dogma that synonymous mutations are generally functionally neutral should be reevaluated. ER -