A HIGHLY POLYMORPHIC MICROSATELLITE IN THE CLASS-II EB GENE ALLOWS TRACING OF MAJOR HISTOCOMPATIBILITY COMPLEX EVOLUTION IN MOUSE

被引:21
作者
SAHA, BK
SHIELDS, JJ
MILLER, RD
HANSEN, TH
SHREFFLER, DC
机构
[1] WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110
[2] WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110
关键词
TANDEM REPEAT; RECOMBINATION HOTSPOT; STANDARD HAPLOTYPE; WILD HAPLOTYPE;
D O I
10.1073/pnas.90.11.5312
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A hallmark of major histocompatibility complex (MHC) genes is their extraordinarily high level of polymorphism. Polymorphic residues on MHC molecules determine which peptide ligands they bind and present to effector T lymphocytes. Although the genetic mechanisms responsible for MHC 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 repeats (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 the basis of length as well as sequence variations, 11 TR alleles were defined in 55 inbred mouse strains, which included MHC recombinant haplotypes and haplotypes derived from different subspecies of mouse. In this extensive sampling, a striking concordance was observed between the serologically identified class II proteins and the associated TR alleles. 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 polymorphism predates the separation of various subspecies of mouse. On the basis of sequence divergence, a genealogical tree has been constructed to depict evolution of the different TR alleles. Finally, evidence is presented that suggests this microsatellite polymorphism is generated by slipped-strand mispairing during DNA replication.
引用
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页码:5312 / 5316
页数:5
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