Bk. Saha et al., A HIGHLY POLYMORPHIC MICROSATELLITE IN THE CLASS-II EB GENE ALLOWS TRACING OF MAJOR HISTOCOMPATIBILITY COMPLEX EVOLUTION IN MOUSE, Proceedings of the National Academy of Sciences of the United Statesof America, 90(11), 1993, pp. 5312-5316
A hallmark of major histocompatibility complex (MHC) genes is their ex
traordinarily high level of polymorphism. Polymorphic residues on MHC
molecules determine which peptide ligands they bind and present to eff
ector T lymphocytes. Although the genetic mechanisms responsible for M
HC polymorphism have been delineated, the timetable and the pathway of
their diversification remain unclear. To trace MHC evolution, we have
characterized a highly polymorphic microsatellite containing tandem r
epeats (TRs) of two tetra-nucleotide units, TGGA and GGCA, located at
the 3' end of the second intron in the class II Eb gene of mouse. On t
he basis of length as well as sequence variations, 11 TR alleles were
defined in 55 inbred mouse strains, which included MHC recombinant hap
lotypes and haplotypes derived from different subspecies of mouse. In
this extensive sampling, a striking concordance was observed between t
he serologically identified class II proteins and the associated TR al
leles. Examination of several strains carrying the same MHC haplotypes
as well as strains carrying recombinant MHC haplotypes indicates that
TR alleles are extremely stable. These observations suggest that TR p
olymorphism predates the separation of various subspecies of mouse. On
the basis of sequence divergence, a genealogical tree has been constr
ucted to depict evolution of the different TR alleles. Finally, eviden
ce is presented that suggests this microsatellite polymorphism is gene
rated by slipped-strand mispairing during DNA replication.