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VH gene segments in the mouse and human genomes
Bernard de Bono1, Martin Madera, Cyrus Chothia
1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. bdb@mrc-lmb.cam.ac.uk
Journal of Molecular Biology
|August 18, 2004
Summary
The mouse genome contains twice as many functional variable heavy (VH) gene segments as humans, with 92 identified in the C57BL/6J strain. These segments, clustered into eight sets, show evolutionary divergence from human VH families.
Area of Science:
- Immunogenetics
- Comparative genomics
Background:
- The variable heavy (VH) gene segments are crucial for antibody diversity.
- Understanding the VH repertoire is essential for immune system research.
Purpose of the Study:
- To comprehensively analyze the mouse VH gene segment repertoire.
- To compare the mouse VH repertoire with that of humans.
Main Methods:
- Examination of the mouse genome sequence.
- Mapping of VH gene segments to chromosome 12.
- Phylogenetic analysis of VH segments.
Main Results:
- 141 VH gene segments identified in a 3 Mb region of mouse chromosome 12.
- 92 functional, 12 strain-specific functional, and 37 pseudogene VH segments in C57BL/6J mice.
- Mouse VH repertoire is twice the size of the human repertoire.
- Mouse and human VH loci show no large-scale similarity.
- 104 functional segments cluster into eight sets, related to human VH families.
- Duplication of segments in the distal locus contributes to the larger mouse repertoire.
- Most VH sequences arose after the divergence of mice and humans.
Conclusions:
- The mouse VH gene repertoire is significantly larger and structurally distinct from the human repertoire.
- Evolutionary analysis reveals independent expansion and divergence of VH gene segments in mice and humans.