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  • Title: Evolution of the variable gene segments and recombination signal sequences of the human T-cell receptor alpha/delta locus.
    Author: Haynes MR, Wu GE.
    Journal: Immunogenetics; 2004 Oct; 56(7):470-9. PubMed ID: 15378298.
    Abstract:
    The T-cell receptor (TCR) alpha and delta loci are particularly interesting because of their unique genomic structure, in that the gene segments for each locus are interspersed. The origin of this remarkable gene segment arrangement is obscure. In this report, we investigated the evolution of the TCRalpha and delta variable loci and their respective recombination signal sequences (RSSs). Our phylogenetic analyses divided the alpha and delta variable gene segments into two major groups each with distinguishing motifs in both the framework and complementarity determining regions (CDRs). Sequence analyses revealed that TCRdelta variable segments share similar CDR2 sequences with immunoglobulin light chain variable segments, possibly revealing similar evolutionary histories. Maximum likelihood analysis of the region on Chromosome 14q11.2 containing the loci revealed two possible ancestral TCR alpha/delta variable segments, TRDV2 and TRAV1-1/ 1-2, respectively. Maximum parsimony revealed different evolutionary patterns between the variable segment and RSS of the same variable gene arguing for dissimilar evolutionary origins. Two models could account for this difference: a V(D)J recombination activity involving embedded heptamer-like motifs in the germline genome, or, more plausibly, an unequal sister chromatid crossing-over. Either mechanism would have resulted in increased diversity for the adaptive immune system.
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