Matassi G, Sharp P M, Gautier C
Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, NG7 2UH, UK.
Curr Biol. 1999;9(15):786-91. doi: 10.1016/s0960-9822(99)80361-3.
Nucleotide substitution rates and G + C content vary considerably among mammalian genes. It has been proposed that the mammalian genome comprises a mosaic of regions - termed isochores - with differing G + C content. The regional variation in gene G + C content might therefore be a reflection of the isochore structure of chromosomes, but the factors influencing the variation of nucleotide substitution rate are still open to question.
To examine whether nucleotide substitution rates and gene G + C content are influenced by the chromosomal location of genes, we compared human and murid (mouse or rat) orthologues known to belong to one of the chromosomal (autosomal) segments conserved between these species. Multiple members of gene families were excluded from the dataset. Sets of neighbouring genes were defined as those lying within 1 centiMorgan (cM) of each other on the mouse genetic map. For both synonymous substitution rates and G + C content at silent sites, neighbouring genes were found to be significantly more similar to each other than sets of genes randomly drawn from the dataset. Moreover, we demonstrated that the regional similarities in G + C content (isochores) and synonymous substitution rate were independent of each other.
Our results provide the first substantial statistical evidence for the existence of a regional variation in the synonymous substitution rate within the mammalian genome, indicating that different chromosomal regions evolve at different rates. This regional phenomenon which shapes gene evolution could reflect the existence of 'evolutionary rate units' along the chromosome.
哺乳动物基因间的核苷酸替换率和G + C含量差异很大。有人提出，哺乳动物基因组由具有不同G + C含量的区域镶嵌体组成，这些区域被称为等密度区。因此，基因G + C含量的区域差异可能反映了染色体的等密度区结构，但影响核苷酸替换率变化的因素仍存在疑问。
为了研究核苷酸替换率和基因G + C含量是否受基因染色体位置的影响，我们比较了已知属于这两个物种间保守的染色体（常染色体）片段之一的人类和鼠类（小鼠或大鼠）直系同源基因。数据集中排除了基因家族的多个成员。相邻基因集被定义为在小鼠遗传图谱上彼此相距1厘摩（cM）以内的基因。对于同义替换率和沉默位点的G + C含量，发现相邻基因彼此之间的相似性明显高于从数据集中随机抽取的基因集。此外，我们证明了G + C含量（等密度区）和同义替换率的区域相似性是相互独立的。
我们的结果为哺乳动物基因组中同义替换率存在区域差异提供了首个实质性的统计证据，表明不同的染色体区域以不同的速率进化。这种塑造基因进化的区域现象可能反映了染色体上“进化速率单位”的存在。
