Polymorphism of the Mouse <i>H‐2</i> Loci

Klein, Jan; Figueroa, Felipe

doi:10.1111/j.1600-065x.1981.tb00361.x

Cited by 152 publications

(70 citation statements)

References 57 publications

(20 reference statements)

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“…Short segmental exchanges of sequence are indeed occurring between widely separated class I MHC loci in laboratory mice (6). Nevertheless it remains controversial whether such processes contribute significantly to the pattern of evolution of class I genes (7), since sequences of class I genes from a closely related murine species such as the rat are not yet available.…”

mentioning

confidence: 99%

Concerted evolution of class I genes in the major histocompatibility complex of murine rodents.

Rada

Lorenzi²,

Powis³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

118

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Full-length cDNA sequences of two class I major histocompatibility complex molecules from the DA strain of Rattus norvegicus are reported. One codes for the classical class I restriction element RTL.Aa, which maps to the locus in the rat major histocompatibility complex homologous to H-2K in the mouse. The other probably codes for a soluble nonclassical class I molecule present in DA rat serum; a short deletion in the fifth exon implies that the translated product will terminate in the membrane-spanning region. These sequences have been compared with mouse classical class I sequences as well as with three published rat class I cDNA partial sequences. The results show, first, that "locus-specific" substitutions from the H-2K, H-2D, and H-2L data set are scrambled in the RTl.A molecule; a majority of these substitutions have H-2D/L-specific features. Second, the data show that the four rat sequences are strikingly similar to one another regardless of locus or haplotype of origin; they share a number of apparently species-specific features that distinguish them all from mouse classical class I sequences, which likewise share distinctive features of their own. The results suggest that segmental sequence exchange plays a major role in determining the evolution of sequence in class I masjor histocompatibility complex molecules.Some multigene families display a degree of species specificity at the level of DNA sequence, as if the whole family were evolving within a species as a unit (1-3). Such concerted evolution has been suspected in mouse major histocompatibility complex (MHC) class I genes because of the lack of clear locus-specific sequence variation distinguishing the widely separated H-2K and H-2D end classical loci (4, 5). Short segmental exchanges of sequence are indeed occurring between widely separated class I MHC loci in laboratory mice (6). Nevertheless it remains controversial whether such processes contribute significantly to the pattern of evolution of class I genes (7), since sequences of class I genes from a closely related murine species such as the rat are not yet available. Rattus norvegicus is in the same subfamily, the Murinae, as the mouse. The rat MHC, RTI, is like H-2 in structure, with a classical class I gene, RTJ.A, at the left end of the MHC in the same location as H-2K and a long array of other class I genes to the right (8). In the middle is a region specifying class II genes that closely resembles the homologous region of H-2 (9). It is most likely that the translocation of class I genes that formed the H-2K end was a unique event occurring shortly before the separation of the rat and mouse lineages (7). Rat class I gene sequences thus provide a stringent test of the concerted evolution hypothesis. With simple divergent evolution alone, the sequence of an RTI.A allele should have greater similarity to H-2K on average than to other rat class I sequences, since RTI.A and H-2K share a more recent common ancestor than either does with genes at the other end of the MHC. If, on the ot...

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mentioning

confidence: 99%

Concerted evolution of class I genes in the major histocompatibility complex of murine rodents.

Rada

Lorenzi²,

Powis³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

118

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“…From sequence comparisons, it is thought that the three presently expressed loci of each gene family were duplicated after the mouse-human divergence (9). At the time when the genes duplicated, their divergence would have been low.…”

Section: Model and Simulation Proceduresmentioning

confidence: 99%

“…In both class I and class II families, there is variation in the number of genes among different species and also in the level of polymorphism (see ref. 9). Apparently, the numbers of normally expressed genes are rather small, usually three but occasionally two or four, in each of the two class families of mouse and human.…”

Section: Model and Simulation Proceduresmentioning

confidence: 99%

Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci.

Ohta

1991

Proc. Natl. Acad. Sci. U.S.A.

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Genes at the major histocompatibility complex (MHC) in mammals are known to have exceptionally high polymorphism and linkage disequilibrium. In addition, these genes form highly complicated gene families that have evolved through gene conversion and unequal crossing-over. It has been shown recently that amino acid substitution at the antigen recognition site (ARS) is more rapid than synonymous substitution, suggesting some kind of positive natural selection working at the ARS. It is highly desirable to know the interactive effect of gene conversion and natural selection on the evolution and variation of MHC gene families. A population genetic model is constructed that incorporates both selection and gene conversion. Diversifying selection is assumed in which sequence diversity is enhanced not only between alleles at the same locus but also between duplicated genes. Expressed and nonexpressed loci are assumed as in the class I gene family of MHC, with gene conversion occurring among all loci. Extensive simulation studies reveal that very weak selection at individual amino acid sites in combination with gene conversion can explain the unusual pattern of evolution and polymorphisms. Here both gene conversion and natural selection contribute to enhancing polymorphism.The exceptionally high levels of polymorphism at the class I and class II loci of the major histocompatibility complex (MHC) in human and mouse have been of great interest for many years (for reviews, see refs. 1 and 2). Based on recent discoveries of the effects of protein structure on antigen recognition and by using reported DNA sequences at these loci, Hughes and Nei (3) have shown that amino acid replacement substitutions occur more frequently than synonymous substitutions at the antigen recognition site (ARS). From this finding, these authors argue that heterozygote advantage (overdominant selection) is operating at the ARS. However, these genes are known to be evolving under various molecular interaction mechanisms such as gene conversion and unequal crossing-over (see refs. 2 and 4-7, for reviews), and overdominant selection at fixed loci would seem to be an insufficient mechanism. It is highly desirable to investigate how natural selection interacts with such molecular mechanisms. In this report, I show that a model that incorporates both selection and gene conversion fits better to the observed facts than the model of simple overdominant selection.Model and Simulation Procedure

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“…A unique feature of the MHC genes, including the Ir genes, is their extreme polymorphism in all of the species that have been studied, Serological H-2 typing of inbred laboratory mice has revealed the existence of 11 alleles at the Ap locus alone (21), It has been estimated that the global number of Ap alleles in wild mice may be tenfold higher. The polymorphism at some of the other H-2 loci is of a comparable magnitude.…”

Section: Location Of Ir Genes In the Genomementioning

confidence: 99%

Immune Response Genes

Werdelin

1982

Allergy

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Polymorphism of the Mouse H‐2 Loci

Cited by 152 publications

References 57 publications

Concerted evolution of class I genes in the major histocompatibility complex of murine rodents.

Concerted evolution of class I genes in the major histocompatibility complex of murine rodents.

Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci.

Immune Response Genes

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