Recent Translocation of Variable and Diversity Segments of the Human Immunoglobulin Heavy Chain from Chromosome 14 to Chromosomes 15 and 16

Abstract

We studied the organization and origin of three orphon regions, VH-F, D5-a, and D5-b, of the human immunoglobulin heavy-chain gene using yeast artificial chromosomes. VH-F and two D5 regions were mapped to chromosome bands 16p11 and 15q11-q12, respectively, by using human/rodent somatic cell hybrids and fluorescence in situ hybridization. No D5 segments were found on chromosome 14, in contradiction to previous reports. The VH-F region consists of 7 VH segments and encompasses 160 kb of DNA. A cluster of VH segments homologous to the VH-F region orphons was found in the region 245-430 kb (V2-26 to V3-11) upstream of the JH cluster on chromosome 14. Comparison of VH sequences between the VH-F and the chromosome 14 loci indicates that the translocation of the VH-F region took place, at the earliest, 20 × 106 years ago. The D5-a and D5-b regions were obtained in two independent contigs. The former contains only D segments in 140 kb of DNA, while the latter carries 3 VH segments downstream of D segments in 110 kb of DNA. V54, one of these VH orphon segments, is about 95% homologous to V1-18, which is located within the putative ancestor of the VH-F region on chromosome 14. Furthermore, the region detected by two DNA probes flanking the V54 segment was found only in the proximity of V1-18 within the 0.8-Mb VH region on chromosome 14. These results suggest that the two orphon loci on chromosomes 15 and 16 may have been translocated simultaneously.