Comparison and evolution of human immunoglobulin VH segments located in the 3' 0.8-megabase region. Evidence for unidirectional transfer of segmental gene sequences

Autor: Takashi Miyata, Yosho Fukita, Ryusuke Matsumura, Hitoshi Nagaoka, Junji Fujikura, Makoto Haino, Shigeo Takaishi, Hidenori Hayashida, Euy Kyun Shin, Fumihiko Matsuda
Rok vydání: 1994
Předmět:
Zdroj: Journal of Biological Chemistry. 269:2619-2626
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(17)41989-2
Popis: 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.
Databáze: OpenAIRE