COMPARISON AND EVOLUTION OF HUMAN IMMUNOGLOBULIN-V(H) SEGMENTS LOCATED IN THE 3' 0.8-MEGABASE REGION - EVIDENCE FOR UNIDIRECTIONAL TRANSFEROF SEGMENTAL GENE-SEQUENCES

Nucleotide sequences of 64 V(H) segments within the 3' 0.8-megabase re gion of the human immunoglobulin germ line V(H) locus were compared wi th trace evolution of human V(H) segments. Based on alignment of the d educed amino acid sequences of 37 functional germ line V(H) segments, a phylogenetic tree was generated using the neighbor-joining method. T he phylogenetic tree clearly supports the previous classification of h uman V(H) segments into six families, which correlate roughly with mou se V(H) families with varying conservation. The human V(H-III) family is most homologous to mouse V(H) segments, suggesting that members of the V(H-III) family may be conserved by some functional constraint. Th e 5'-flanking region of each family has a family-specific structure. T he sequenced 64 V(H) segments include 31 pseudogenes, of which 24 were highly conserved. Unidirectional transfer of segmental sequences was identified within the V(H-III) and V(H-IV) families, providing clear e xamples of germ line gene conversion. Such gene conversion may contrib ute to conserve structures of pseudo-V(H) segments. Comparison of the V(H-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.