Sitnikova T, Nei M
Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park 16802, USA.
Mol Biol Evol. 1998 Jan;15(1):50-60. doi: 10.1093/oxfordjournals.molbev.a025846.
The major source of immunoglobulin diversity is variation in DNA sequence among multiple copies of variable region (V) genes of the heavy- and light-chain multigene families. In order to clarify the evolutionary pattern of the multigene family of immunoglobulin light kappa chain V region (V kappa) genes, phylogenetic analyses of V kappa genes from humans and other vertebrate species were conducted. The results obtained indicate that the V kappa genes so far sequenced can be grouped into three major monophyletic clusters, the cartilaginous fish, bony fish and amphibian, and mammalian clusters, and that the cartilaginous fish cluster first separated from the rest of the V kappa genes and then the remaining two clusters diverged. The mammalian V kappa genes can further be divided into 10 V kappa groups, 7 of which are present in the human genome. Human and mouse V kappa genes from different V kappa groups are intermingled rather than clustered on the chromosome, and there are a large number of pseudogenes scattered on the chromosome. This indicates that the chromosomal locations of V kappa genes have been shuffled many times by gene duplication, deletion, and transposition in the evolutionary process and that many genes have become nonfunctional during this process. This mode of evolution is consistent with the model of birth-and-death evolution rather than with the model of concerted evolution. An analysis of duplicate V kappa functional genes and pseudogenes in the human genome has indicated that pseudogenes evolve faster than functional genes but that the rate of nonsynonymous nucleotide substitution in the complementarity-determining regions of V kappa genes has been enhanced by positive Darwinian selection.
免疫球蛋白多样性的主要来源是重链和轻链多基因家族可变区（V）基因多个拷贝之间的DNA序列变异。为了阐明免疫球蛋白轻链κ链V区（Vκ）基因多基因家族的进化模式，对人类和其他脊椎动物物种的Vκ基因进行了系统发育分析。所得结果表明，迄今为止测序的Vκ基因可分为三个主要的单系簇，即软骨鱼、硬骨鱼和两栖动物簇以及哺乳动物簇，并且软骨鱼簇首先与其余的Vκ基因分离，然后其余两个簇分化。哺乳动物的Vκ基因可进一步分为10个Vκ组，其中7个存在于人类基因组中。来自不同Vκ组的人类和小鼠Vκ基因在染色体上相互交织而不是聚集在一起，并且染色体上散布着大量假基因。这表明在进化过程中，Vκ基因的染色体位置通过基因复制、缺失和转座多次重排，并且在此过程中有许多基因变得无功能。这种进化模式与生死进化模型一致，而不是与协同进化模型一致。对人类基因组中重复的Vκ功能基因和假基因的分析表明，假基因的进化速度比功能基因快，但Vκ基因互补决定区的非同义核苷酸替换率因正向达尔文选择而提高。
