Haino M, Hayashida H, Miyata T, Shin E K, Matsuda F, Nagaoka H, Matsumura R, Taka-ishi S, Fukita Y, Fujikura J
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
J Biol Chem. 1994 Jan 28;269(4):2619-26.
Nucleotide sequences of 64 VH segments within the 3' 0.8-megabase region of the human immunoglobulin germ line VH locus were compared with trace evolution of human VH segments. Based on alignment of the deduced amino acid sequences of 37 functional germ line VH segments, a phylogenetic tree was generated using the neighbor-joining method. The phylogenetic tree clearly supports the previous classification of human VH segments into six families, which correlate roughly with mouse VH families with varying conservation. The human VH-III family is most homologous to mouse VH segments, suggesting that members of the VH-III family may be conserved by some functional constraint. The 5'-flanking region of each family has a family-specific structure. The sequenced 64 VH segments include 31 pseudogenes, of which 24 were highly conserved. Unidirectional transfer of segmental sequences was identified within the VH-III and VH-IV families, providing clear examples of germ line gene conversion. Such gene conversion may contribute to conserve structures of pseudo-VH segments. Comparison of the VH-IV family members indicates that recent repeated duplications and frequent gene conversions are responsible for strong conservation of this family, although functional selection is not completely excluded.
将人类免疫球蛋白种系VH基因座3'端0.8兆碱基区域内64个VH区段的核苷酸序列与人类VH区段的微量进化进行了比较。基于37个功能性种系VH区段推导的氨基酸序列比对，采用邻接法构建了系统发育树。该系统发育树明确支持了先前将人类VH区段分为六个家族的分类，这些家族与小鼠VH家族大致相关，且保守程度各异。人类VH-III家族与小鼠VH区段同源性最高，这表明VH-III家族成员可能受到某些功能限制而得以保守。每个家族的5'侧翼区域具有家族特异性结构。所测序的64个VH区段包括31个假基因，其中24个高度保守。在VH-III和VH-IV家族中鉴定出了区段序列的单向转移，这为种系基因转换提供了明确实例。这种基因转换可能有助于保守假VH区段的结构。对VH-IV家族成员的比较表明，尽管不能完全排除功能选择，但近期的重复复制和频繁的基因转换是该家族高度保守的原因。
