Johnson G, Wu T T
Department of Biochemistry, Northwestern University, Evanston, Illinois 60208, USA.
Genetics. 1997 Mar;145(3):777-86. doi: 10.1093/genetics/145.3.777.
Mutations in immunoglobulin V-genes can be due to gene multiplication, allelic variations, mutations induced by antigens or somatic mutations, etc., and various combinations of these. Since the number of different mouse lambda light V-gene nucleotide sequences is relatively small, a pairwise comparison between these sequences can provide a rough idea as to the contributions of the above mechanisms to the number of nucleotide differences between sequences. A plot of occurrences against the number of differences suggests that differences between one to five can be attributed to somatic mutations. Six to 12 differences can be allelic. Thirteen to 17 may be due to allelic variations together with somatic mutations. Differences > 17 appear to be derived from gene multiplication. Although these numbers are most likely somewhat different in humans, they can nevertheless provide a rough guide to sort out the effect of gene multiplication. Estimations of human heavy, kappa and lambda light chain immunoglobulin V-genes are in reasonably good agreement with recent experimental studies. For mouse kappa light and heavy chains, our estimations can provide some insight to future analyses by direct sequencing of these gene segments.
免疫球蛋白V基因中的突变可能源于基因倍增、等位基因变异、抗原诱导的突变或体细胞突变等，以及这些因素的各种组合。由于不同小鼠λ轻链V基因核苷酸序列的数量相对较少，这些序列之间的成对比较可以大致了解上述机制对序列间核苷酸差异数量的贡献。差异出现次数与差异数量的关系图表明，1至5个差异可归因于体细胞突变。6至12个差异可能是等位基因造成的。13至17个差异可能是等位基因变异与体细胞突变共同作用的结果。大于17个差异似乎源于基因倍增。尽管这些数字在人类中很可能有所不同，但它们仍可为理清基因倍增的影响提供一个大致的指导。对人类重链、κ链和λ轻链免疫球蛋白V基因的估计与最近的实验研究相当吻合。对于小鼠κ轻链和重链，我们的估计可为未来通过直接测序这些基因片段进行的分析提供一些见解。
