Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias.
Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias.
复制标题
DOI：
10.1093/molbev/msab099
复制
发表时间：
2021-07-29
影响因子：
10.7
通讯作者：
Wolf JB
中科院分区：
文献类型：
--
作者：
de Oliveira JL;Morales AC;Hurst LD;Urrutia AO;Thompson CRL;Wolf JB
替代同义密码子通常以不相等的频率使用。传统上，这种密码子使用偏好（CUB）的研究试图通过假设偏离预测的中性平衡捕获选择来将中性的影响与选择力分开。然而，GC偏向的基因转换（gBGC）也可能导致偏离中性零。或者，已经从高表达基因中的CUB推断出选择，但是这种方法的准确性尚未被广泛测试，并且gBGC可以干扰这种外推（例如，如果表达和基因转化率共变）。因此，在没有gBGC的物种中检查与突变无效的偏差至关重要。为了实现这一目标，我们在高度AT丰富的盘基网柄藻基因组中进行了这样的分析，在那里我们没有发现gBGC的证据。我们推断中性CUB突变平衡下量化“适应性密码子偏好”，一个nontautuminescent基因组范围内的相对选择强度驱动CUB的定量措施。我们观察到纯化选择的签名与有利于适应性密码子偏好的选择一致。优选的密码子不是富含GC的，强调了与gBGC的独立性。表达相关的“偏好”在很大程度上匹配自适应密码子偏好，但并不完全捕获所有基因的选择成形模式的影响，这表明选择性限制与高表达特异性相关。我们观察到的模式与mRNA翻译和稳定性形成适应性密码子偏好的影响一致。因此，我们的方法来量化适应性密码子偏好提供了一个框架，用于推断选择的来源，形状CUB在基因组内的不同背景。
Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.
登录
查看更多内容
影响因子：
9.9
作者：
Bentele, Kajetan;Saffert, Paul;Bluethgen, Nils
通讯作者：
Bluethgen, Nils
影响因子：
4.5
作者：
Charneski CA;Honti F;Bryant JM;Hurst LD;Feil EJ
通讯作者：
Feil EJ
DOI：
10.1073/pnas.1814425116
发表时间：
2019-02-05
影响因子：
11.1
作者：
Bloomfield, Gareth;Paschke, Peggy;Urushihara, Hideko
通讯作者：
Urushihara, Hideko
影响因子：
4
作者：
Duret, L
通讯作者：
Duret, L
影响因子：
5.6
作者：
de Smit, MH;van Duin, J
通讯作者：
van Duin, J