A New Mehtod For Detecting Natural Selection At The Level Of Nucleotide Sites And Origin And Evolution Of New Exons In The Human CDYL Gene

Although noncoding regions play an important role in gene expression and regulation, it is difficult to detect natural selection at this level. Recently, some studies use the ratio (ω) between the nucleotide substitution rate in the detected regions and the nucleotide substitution rate in neutral regions as an indicator to detect natural selection in noncoding regions. ωwill be equal to 1 when a region is evolving neutrally, while ω<1 indicates purifying selection, and ω>1 suggests positive selection. However, to the noncoding regions, it's more informative to identify those nucleotide sites under positive selection. We developed a new maximum-likelihood method to detect natural selection at the nucleotide site level and to identify those nucleotide sites that may contribute to functional divergence. The results of this study show as follows: 1. This method can be applied to both coding regions and noncoding regions. 2. Appling this method to HIV-1 envelope gene to predict positive selected sites, we found that our results are similar to the results obtained by Yang's method. It suggests that this method is efficient to detect natural selection on nucleotide sites in coding regions. 3. We also applied our method to analyze 5'UTR of CTGF. The results demonstrate that this method can predict positive selected sites in noncoding region too. Given the rapid accumulation of genomic data, we have known that there exists gene number difference among organisms. In the past decade, we have started to understand the mechanism of origin and evolution of new genes. We also know that fixation of new genes in population is driven by natural selection. However, as the basic unit of genes, the origin and evolution of exons remain largely unknown. In high eukaryocytes, alternative splicing is an important resource of protein variation and novelty. So origin and evolution of exon is an important question in evolutionary biology. Through homologue gene comparison, we identified new exons in human CDYL gene. This study analyzed the origination and evolution of these new exons in detail. The results of this study show as follows: 1. The alternative splicing form a of human CDYL gene is its longest transcript. The exon 2 and exon 3 of this splicing form originated recently. 2. The two new exons experience fast evolution in human lineage. It suggestes that this fast evolution is driven by positive selection. 3. Through population genetics analysis, the results showed that exon 3 was subjected to strong balance selction.