Centre d'Ecologie Fonctionnelle et Evolutive, CNRS, Université de Montpellier, Université Paul Valéry Montpellier 3, Ecole Pratique des Hautes Etudes, Institut de Recherche pour le Développement, Montpellier, France.
Genome Biol Evol. 2021 Sep 1;13(9). doi: 10.1093/gbe/evab097.
Protein coding genes can contain specific motifs within their nucleotide sequence that function as a signal for various biological pathways. The presence of such sequence motifs within a gene can have beneficial or detrimental effects on the phenotype and fitness of an organism, and this can lead to the enrichment or avoidance of this sequence motif. The degeneracy of the genetic code allows for the existence of alternative synonymous sequences that exclude or include these motifs, while keeping the encoded amino acid sequence intact. This implies that locally, there can be a selective pressure for preferentially using a codon over its synonymous alternative in order to avoid or enrich a specific sequence motif. This selective pressure could-in addition to mutation, drift and selection for translation efficiency and accuracy-contribute to shape the codon usage bias. In this review, we discuss patterns of avoidance of (or enrichment for) the various biological signals contained in specific nucleotide sequence motifs: transcription and translation initiation and termination signals, mRNA maturation signals, and antiviral immune system targets. Experimental data on the phenotypic or fitness effects of synonymous mutations in these sequence motifs confirm that they can be targets of local selection pressures on codon usage. We also formulate the hypothesis that transposable elements could have a similar impact on codon usage through their preferred integration sequences. Overall, selection on codon usage appears to be a combination of a global selection pressure imposed by the translation machinery, and a patchwork of local selection pressures related to biological signals contained in specific sequence motifs.
蛋白质编码基因的核苷酸序列中含有特定的基序，这些基序作为各种生物途径的信号发挥作用。基因中存在这样的序列基序会对生物体的表型和适应性产生有益或有害的影响，这可能导致该序列基序的富集或回避。遗传密码的简并性允许存在排除或包含这些基序的替代同义序列，同时保持编码的氨基酸序列完整。这意味着在局部范围内，为了避免或富集特定的序列基序，可能会存在优先使用某个密码子而不是其同义替代物的选择压力。除了突变、漂变和对翻译效率和准确性的选择之外，这种选择压力可能有助于塑造密码子使用偏好。在这篇综述中，我们讨论了回避（或富集）特定核苷酸序列基序中包含的各种生物信号的模式：转录和翻译起始和终止信号、mRNA 成熟信号和抗病毒免疫系统靶标。这些序列基序中同义突变的表型或适应性影响的实验数据证实，它们可能是密码子使用局部选择压力的目标。我们还提出了一个假设，即转座元件可能通过其偏好的整合序列对密码子使用产生类似的影响。总的来说，密码子使用的选择似乎是由翻译机制施加的全局选择压力，以及与特定序列基序中包含的生物信号相关的局部选择压力的组合。
