Synonymous but not the same: the causes and consequences of codon bias

Abstract

Codon usage varies widely between species, between genes in a genome and between sites in a gene. Explanations for natural variation in codon usage fall into two categories: mutational and selective. Mutational mechanisms are responsible for most codon-usage variation between species; by contrast, selection for translation efficiency accounts for much of the systematic variation across a genome (except in mammals). Translationally efficient codons may increase elongation rate, accuracy or both. Rapid elongation should not be expected to influence protein yield per mRNA molecule for an endogenous gene, but it may be relevant for an overexpressed transgene. The codons that provide efficient translation of an overexpressed transgene may differ from the efficient codons for an endogenous gene. High-throughput measurements of endogenous mRNA levels, protein levels and ribosomal occupancies provide a detailed description of translation processes. Libraries of randomized genes can elucidate design principles for efficient transgene expression, even without uncovering underlying mechanisms.