Evolution of the immunoglobulin heavy chain variable region (Igh-V) locus in the genusMus

Tutter, Adele; Riblet, Roy

doi:10.1007/bf02425271

Cited by 22 publications

(10 citation statements)

References 58 publications

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“…A representative example is the 129S1/SvImJ-specific coldspot on distal chromosome 12 ( Figure 8A). This coldspot spans the Igh locus, a cluster of duplicated genes encoding immunoglobulin heavy-chain peptides, which is known to be highly polymorphic in wild mice (Tutter and Riblet 1989) and classical inbred strains (Retter et al 2007). At least three classical Igh haplotypes are segregating in the DO: Igh b (C57BL/ 6J, NOD/ShiLtJ); Igh e (A/J) and Igh a (129S1/SvImJ).…”

Section: Haplotype-specific Coldspots Are Relatively Rarementioning

confidence: 99%

Structural Variation Shapes the Landscape of Recombination in Mouse

et al. 2017

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Meiotic recombination is an essential feature of sexual reproduction that ensures faithful segregation of chromosomes and redistributes genetic variants in populations. Multiparent populations such as the Diversity Outbred (DO) mouse stock accumulate large numbers of crossover (CO) events between founder haplotypes, and thus present a unique opportunity to study the role of genetic variation in shaping the recombination landscape. We obtained high-density genotype data from [Formula: see text] DO mice, and localized 2.2 million CO events to intervals with a median size of 28 kb. The resulting sex-averaged genetic map of the DO population is highly concordant with large-scale (order 10 Mb) features of previously reported genetic maps for mouse. To examine fine-scale (order 10 kb) patterns of recombination in the DO, we overlaid putative recombination hotspots onto our CO intervals. We found that CO intervals are enriched in hotspots compared to the genomic background. However, as many as [Formula: see text] of CO intervals do not overlap any putative hotspots, suggesting that our understanding of hotspots is incomplete. We also identified coldspots encompassing 329 Mb, or [Formula: see text] of observable genome, in which there is little or no recombination. In contrast to hotspots, which are a few kilobases in size, and widely scattered throughout the genome, coldspots have a median size of 2.1 Mb and are spatially clustered. Coldspots are strongly associated with copy-number variant (CNV) regions, especially multi-allelic clusters, identified from whole-genome sequencing of 228 DO mice. Genes in these regions have reduced expression, and epigenetic features of closed chromatin in male germ cells, which suggests that CNVs may repress recombination by altering chromatin structure in meiosis. Our findings demonstrate how multiparent populations, by bridging the gap between large-scale and fine-scale genetic mapping, can reveal new features of the recombination landscape.

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Section: Haplotype-specific Coldspots Are Relatively Rarementioning

confidence: 99%

Structural Variation Shapes the Landscape of Recombination in Mouse

et al. 2017

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“…The O. c. algirus sequences were therefore aligned with all published rabbit genomic V H sequences. Rabbit V H sequences belong to the class C (40,41). For this reason, we used, as outgroups in phylogenetic analysis, vertebrate V H sequences that are separated by a relatively short branch from the root of class C sequences (human V H 3, camel V H , and duck V H ).…”

Section: Inferring V H Genes Expressed In O C Algirusmentioning

confidence: 99%

Allelic Variation at theVHaLocus in Natural Populations of Rabbit (Oryctolagus cuniculus, L.)

Esteves

Lanning

Ferrand

et al. 2004

The Journal of Immunology

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The large interallelic distances between the three rabbit Ig V(H)a lineages, a1, a2 and a3, suggest that the persistence time of the V(H)a polymorphism could amount to 50 million years, which is much longer than that of MHC polymorphisms. Rabbit originated in the Iberian Peninsula where two subspecies coexist, one of which is confined to Southwestern Iberia (Oryctolagus cuniculus algirus). We studied the V(H) loci in the original species range to obtain a better understanding of the evolutionary history of this unusual polymorphism. Serological surveys revealed that sera from the subspecies algirus, when tested with V(H)a locus-specific alloantisera, showed either cross-reactivity ("a-positive" variants) or no reaction at all ("a-blank"). Using RT-PCR, we determined 120 sequences of rearranged V(H) genes expressed in seven algirus rabbits that were typed as either a-positive or a-blank. The data show that the V(H) genes transcribed in a-positive rabbits are closely related to the V(H)1 alleles of domestic rabbits. In contrast, a-blank rabbits were found to preferentially use V(H) genes that, although clearly related to the known V(H)a genes, define a new major allotypic lineage, designated a4. The a4 sequences have hallmark rabbit V(H)a residues together with a number of unprecedented amino acid changes in framework region 2 and 3. The net protein distances between the V(H)a4 and the V(H)a1, a2, and a3 lineages were 20, 29, and 21% respectively. We conclude that at least four distantly related lineages of the rabbit V(H)a locus exist, one of which seems to be endemic in the Iberian range.

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“…Mutations at only critical positions in relatively conserved CDR structures (Ohno et al 1985;Cothia et al 1989) would be sufficient to recover the original specificity; (3) The catastrophic contraction of the V gene repertoire due to unequal crossingover undoubtedly occurs (Tutter et al 1989a), but such individuals may be eliminated in a natural environment. However, the loss of a certain repertoire might be compensated for by other family members; (4) V genes have to be expressed in B cells of reasonable clonal size to have a protective role against pathogens (Langman and Cohn 1987).…”

Section: Significance Of the V Gene Familymentioning

confidence: 99%

Evolution of immunoglobulin heavy chain variable region genes: a VH family can last for 150?200 million years or longer

Andersson

Matsunaga

1995

Immunogenetics

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Many immunoglobulin variable region (IgV) genes are present in the vertebrate genome and provide a basis for antibody diversity. IgV genes have been classified into distinct families according to DNA sequence similarity. Comparisons of VH and VL genes from two mammalian species (mouse and human) have led to the conclusion that some V gene families are stable over 65 million years of evolution. Here we show that a VH family can be stable for 150-200 million years or longer. This conclusion is drawn from our extensive comparison of VH genes between two species of low vertebrates (rainbow trout and catfish), and from the estimation of species divergence time by the substitution rate of an IgM constant domain. The estimated speed of VH gene evolution explains the moderate degree of sequence similarity in VH gene families between a mammal (mouse) and a teleost (rainbow trout). The distribution of species-specific amino acid residues in certain VH families indicates that the process of sequence homogenization plays a major role in shaping the V gene family.

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Evolution of the immunoglobulin heavy chain variable region (Igh-V) locus in the genusMus

Cited by 22 publications

References 58 publications

Structural Variation Shapes the Landscape of Recombination in Mouse

Structural Variation Shapes the Landscape of Recombination in Mouse

Allelic Variation at theVHaLocus in Natural Populations of Rabbit (Oryctolagus cuniculus, L.)

Evolution of immunoglobulin heavy chain variable region genes: a VH family can last for 150?200 million years or longer

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