Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 21, Pages 11415-11420Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.21.11415
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The Ig and T cell receptor (TCR) loci have an exceptionally dynamic evolutionary history, but the mechanisms responsible remain a subject of speculation. Ig and TCR genes are unique in vertebrates in that they are assembled from V, D, and J segments by site-specific recombination in developing lymphocytes. Here we examine the extent to which the V(D)J recombination in germline cells may have been responsible for remodeling Ig and TCR loci in mammals by asking whether gene segments have evolved as a unit, or whether, instead, recombination signal sequences (RSSs) and coding sequences have different phylogenies, Four distinct types of Rss have been defined in the human Ig heavy-chain variable region (VH) locus, namely H1, H2, H3, and H5, and no other RSS type has been detected in other mammalian species. There is a well-supported discrepancy between the evolutionary history of the RSSs as compared with the VH coding sequences: the RSS type HZ of one VH gene segment has clearly become replaced by a 855 type H3 during mammalian evolution, between 115 and 65 million years ago. Two general models might explain the 855 swap: the first involves an unequal crossing over, and the second implicates germline activation of V(D)J recombination. The VH-H2/RSS-H3 recombination product has likely been selected during the evolution of mammals because it provides better V(D)J recombination efficiency.
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