Bustamante Carlos D, Nielsen Rasmus, Hartl Daniel L
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Mol Biol Evol. 2002 Jan;19(1):110-7. doi: 10.1093/oxfordjournals.molbev.a003975.
We present a new likelihood method for detecting constrained evolution at synonymous sites and other forms of nonneutral evolution in putative pseudogenes. The model is applicable whenever the DNA sequence is available from a protein-coding functional gene, a pseudogene derived from the protein-coding gene, and an orthologous functional copy of the gene. Two nested likelihood ratio tests are developed to test the hypotheses that (1) the putative pseudogene has equal rates of silent and replacement substitutions; and (2) the rate of synonymous substitution in the functional gene equals the rate of substitution in the pseudogene. The method is applied to a data set containing 74 human processed-pseudogene loci, 25 mouse processed-pseudogene loci, and 22 rat processed-pseudogene loci. Using the informatics resources of the Human Genome Project, we localized 67 of the human-pseudogene pairs in the genome and estimated the GC content of a large surrounding genomic region for each. We find that, for pseudogenes deposited in GC regions similar to those of their paralogs, the assumption of equal rates of silent and replacement site evolution in the pseudogene is upheld; in these cases, the rate of silent site evolution in the functional genes is approximately 70% the rate of evolution in the pseudogene. On the other hand, for pseudogenes located in genomic regions of much lower GC than their functional gene, we see a sharp increase in the rate of silent site substitutions, leading to a large rate of rejection for the pseudogene equality likelihood ratio test.
我们提出了一种新的似然方法，用于检测推定假基因中同义位点的受限进化以及其他形式的非中性进化。只要有来自蛋白质编码功能基因、源自该蛋白质编码基因的假基因以及该基因的直系同源功能拷贝的DNA序列，该模型就适用。我们开发了两个嵌套的似然比检验，以检验以下假设：（1）推定假基因的沉默替换率和替换替换率相等；（2）功能基因中的同义替换率等于假基因中的替换率。该方法应用于一个包含74个人类加工假基因位点、25个小鼠加工假基因位点和22个大鼠加工假基因位点的数据集。利用人类基因组计划的信息资源，我们在基因组中定位了67对人类假基因，并估计了每个假基因周围大片基因组区域的GC含量。我们发现，对于沉积在与其旁系同源基因相似的GC区域中的假基因，假基因中沉默位点和替换位点进化速率相等的假设成立；在这些情况下，功能基因中沉默位点的进化速率约为假基因进化速率的70%。另一方面，对于位于GC含量远低于其功能基因的基因组区域中的假基因，我们观察到沉默位点替换率急剧增加，导致假基因相等似然比检验的拒绝率大幅上升。
