Estimation of genetic distances from human and mouse introns

BACKGROUND: Using genetic distances measured from exons, it has been observed that the mutation rate is not constant along mammalian chromosomes. Exons constitute only 1% of the human genome, however, and thus they cannot provide a complete picture of the mutational variation in the genome. RESULTS: I calculated genetic distances between 504 human introns and their orthologous mouse counterparts from a set of 63 pairs of human and mouse genes scattered through the genome using a recently developed method that can extract reliably aligned regions from the introns in an objective manner. I found a significant correlation between the genetic distance measured in the conserved intron segments and the synonymous and nonsynonymous distances measured in the corresponding coding exons, indicating that genes with fast-evolving exons tend to have fast-evolving introns, and vice versa. CONCLUSIONS: These results indicate that introns, which extend over almost a quarter of the human genome, contain useful information for fully understanding the mutational dynamics of human and mouse genomes. This work also supports the idea that there is a mutational force that fluctuates nonrandomly along the genome, and shows for the first time that this force affects the introns and the synonymous and nonsynonymous positions in the exons of the genes simultaneously.

背景：基于外显子（exon）测得的遗传距离，已有研究发现哺乳动物染色体上的突变率并非恒定不变。然而，外显子仅占人类基因组的1%，因此无法完整反映基因组内的突变变异情况。
结果：本研究从散布于全基因组的63对人-鼠基因集合中，采用新近开发的可客观提取内含子（intron）中可靠比对区域的方法，计算了504个人类内含子与其小鼠同源对应内含子之间的遗传距离。研究发现，保守内含子区段测得的遗传距离，与对应编码外显子中的同义替换距离及非同义替换距离存在显著相关性，这表明外显子进化较快的基因，其内含子的进化通常也较快，反之亦然。
结论：上述结果表明，占人类基因组近四分之一的内含子，可为完整解析人、鼠基因组的突变动态提供有效信息。本研究同时支持“基因组上存在非随机波动的突变压力”这一观点，并首次证实该突变压力可同时作用于内含子以及基因外显子内的同义、非同义位点。