Widespread position-specific conservation of synonymous rare codons within coding sequences

Synonymous rare codons are considered to be sub-optimal for gene expression because they are translated more slowly than common codons. Yet surprisingly, many protein coding sequences include large clusters of synonymous rare codons. Rare codons at the 5’ terminus of coding sequences have been shown to increase translational efficiency. Although a general functional role for synonymous rare codons farther within coding sequences has not yet been established, several recent reports have identified rare-to-common synonymous codon substitutions that impair folding of the encoded protein. Here we test the hypothesis that although the usage frequencies of synonymous codons change from organism to organism, codon rarity will be conserved at specific positions in a set of homologous coding sequences, for example to tune translation rate without altering a protein sequence. Such conservation of rarity–rather than specific codon identity–could coordinate co-translational folding of the encoded p...同义稀有密码子（synonymous rare codons）通常被认为对基因表达存在次优效应，因其翻译速率低于常用密码子。然而令人意外的是，诸多蛋白质编码序列中存在大量同义稀有密码子簇。已有研究证实，编码序列5'端的稀有密码子可提升翻译效率。尽管目前尚未明确编码序列内部更深位置的同义稀有密码子的普遍功能，但近期多项研究已发现，将稀有同义密码子替换为常用同义密码子会损害编码蛋白的折叠过程。本研究旨在验证如下假说：尽管不同物种间同义密码子的使用频率存在差异，但一组同源编码序列的特定位置上的密码子稀有性会得以保留，例如在不改变蛋白质序列的前提下调控翻译速率。这种对密码子稀有性的保留（而非特定密码子本身），可协调编码蛋白的共翻译折叠过程……