Santpere Gabriel, Carnero-Montoro Elena, Petit Natalia, Serra François, Hvilsom Christina, Rambla Jordi, Heredia-Genestar Jose Maria, Halligan Daniel L, Dopazo Hernan, Navarro Arcadi, Bosch Elena
Departament de Ciències Experimentals i la Salut, Institute of Evolutionary Biology (UPF-CSIC), Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
Structural Genomics Team, Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.
Genome Biol Evol. 2015 May 14;7(6):1490-505. doi: 10.1093/gbe/evv082.
We set out to investigate potential differences and similarities between the selective forces acting upon the coding and noncoding regions of five different sets of genes defined according to functional and evolutionary criteria: 1) two reference gene sets presenting accelerated and slow rates of protein evolution (the Complement and Actin pathways); 2) a set of genes with evidence of accelerated evolution in at least one of their introns; and 3) two gene sets related to neurological function (Parkinson's and Alzheimer's diseases). To that effect, we combine human-chimpanzee divergence patterns with polymorphism data obtained from target resequencing 20 central chimpanzees, our closest relatives with largest long-term effective population size. By using the distribution of fitness effect-alpha extension of the McDonald-Kreitman test, we reproduce inferences of rates of evolution previously based only on divergence data on both coding and intronic sequences and also obtain inferences for other classes of genomic elements (untranslated regions, promoters, and conserved noncoding sequences). Our results suggest that 1) the distribution of fitness effect-alpha method successfully helps distinguishing different scenarios of accelerated divergence (adaptation or relaxed selective constraints) and 2) the adaptive history of coding and noncoding sequences within the gene sets analyzed is decoupled.
1）两组参考基因集，其蛋白质进化速率分别呈现加速和缓慢的情况（补体和肌动蛋白途径）；2）一组基因，其至少一个内含子有加速进化的证据；3）两组与神经功能相关的基因集（帕金森病和阿尔茨海默病）。为此，我们将人类与黑猩猩的分化模式与从对20只中部黑猩猩进行目标重测序获得的多态性数据相结合，中部黑猩猩是我们亲缘关系最近且长期有效种群规模最大的近亲。通过使用适应性效应分布——麦克唐纳-克赖特曼检验的α扩展，我们重现了先前仅基于编码和内含子序列的分歧数据得出的进化速率推断，并且还获得了其他类型基因组元件（非翻译区、启动子和保守非编码序列）的推断。我们的结果表明：1）适应性效应分布——α方法成功地有助于区分加速分化的不同情况（适应或放松的选择约束）；2）所分析基因集内编码和非编码序列的适应性历史是解耦的。
