Typing of artiodactyl <i>MHC‐DRB</i> genes with the help of intronic simple repeated DNA sequences

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high levels of genetic diversity widely observed at the major histocompatibility complex (MHC) of vertebrate hosts are consistent with the hypothesis of parasite-driven balancing selection acting to maintain MHC genetic diversity. To date, however, empirical evidence in support of this hypothesis, especially from natural populations, has been lacking. A large unmanaged population of Soay sheep (Ovis aries L.) is used to investigate associations between MHC variation, juvenile survival, and parasite resistance. We show in an unmanaged, nonhuman population that allelic variation within the MHC is significantly associated with differences in both juvenile survival and resistance to intestinal nematodes. Certain MHC alleles are associated with low survivorship probabilities and high levels of parasitism or vice versa. We conclude that parasites are likely to play a major role in the maintenance of MHC diversity in this population.Maintenance of genetic diversity at the major histocompatibility complex (MHC) of vertebrates has become a paradigm for the manner in which genetic diversity may be maintained in natural populations (1). The MHC consists of a group of closely linked genes involved in antigen presentation to the vertebrate immune system (2) and is remarkable in that extremely high levels of heterozygosity are commonly observed at certain genes contained within the complex (1, 3).Several lines of evidence indicate that the high allelic diversity observed at the MHC is maintained through some form of selective force. First, where genealogies of MHC allele sequences have been constructed from a number of species [for example, primates (4) and felines (5)] it is observed that the divergence of allelic MHC lineages predates the speciation event giving rise to separate taxa. This suggests the action of some form of balancing selection over long periods of evolutionary time. Second, comparisons of allelic sequences present within mice and human populations indicate that the rate of nonsynonymous (coding) substitution exceeds the rate of synonymous (noncoding) substitution at the antigen presenting site, thus favoring new MHC variants and increasing diversity (6-8). Finally, in human populations the large numbers of alleles present at MHC loci show a relatively even distribution, leading to higher levels of heterozygosity than may be explained under neutral theory (9) and suggesting the action of recent balancing selection. So far, however, most studies of MHC polymorphism have been confined to human or semicaptive mouse populations, and there is a paucity of population-based studies within natural populations of other vertebrates.Despite strong evidence for balancing selection at the MHC, the mechanisms behind maintenance of MHC polymorphism are still unclear. Two broad categories of selective mechanisms have been proposed. Reproductive...

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“…1. The markers OLADRB and OLADRBps are located within MHC class II expressed and nonexpressed genes, respectively (36,37). OMHC1 is Proc.…”

Section: Studymentioning

confidence: 99%

Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.)

Paterson

Wilson

Pemberton

1998

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

431

386

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“…The markers OLADRB and OLADRBps are located within MHC class II expressed and non-expressed genes respectively (Blattman & Beh 1992;Schwaiger et al 1993), OMHC1 is located within the MHC class I region (Groth & Wetherall 1994) and BM1815 and BM1818 (Bishop et al 1994 were used as £anking marker controls.…”

Section: (D) Mhc Markersmentioning

confidence: 99%

No evidence for major histocompatibility complex–dependent mating patterns in a free–living ruminant population

Paterson

Pemberton

1997

Proc. R. Soc. Lond. B

124

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Conventionally, the extraordinary diversity of the vertebrate major histocompatibility complex (MHC) is thought to have evolved in response to parasites and pathogens a¡ecting ¢tness. More recently, reproductive mechanisms such as disassortative mating have been suggested as alternative mechanisms maintaining MHC diversity. A large unmanaged population of Soay sheep (Ovis aries L.) was used to investigate reproductive mechanisms in the maintenance of MHC diversity. Animals were sampled as new-born lambs and between 887 and 1209 individuals were typed at each of ¢ve microsatellite markers located either within or £anking the ovine MHC. All loci were in Hardy^Weinberg proportions. A novel likelihood-based approach was developed to analyse mating patterns using paternity data. No evidence for non-random mating with respect to MHC markers was found using this technique. We conclude that MHC diversity in the St Kildan Soay sheep population is unlikely to be maintained by mating preferences and that, in contrast with evidence from experimental mice populations, MHC variation plays no role in the mating structure of this population.

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“…The genotypic makeup of the sheep at three microsatellites loci that are closely linked to MHC genes was determined. These are: (1) OLADRB (Schwaiger et al, 1993) located in the second intron of OvarDRB1, a class II MHC gene; (2) OLADRBps located in the intron between the fifth and the sixth exons of OLADRBps (Blattman and Beh, 1992); and (3) OMHC1 in the third intron of the OMHC1 class I locus (Groth and Wetherall, 1994). OLADRB is an interrupted and complex microsatellite with (gt) n (ga) m as the basic motif.…”

Section: Methodsmentioning

confidence: 99%

“…Microsatellite loci located within the MHC region have received increasing attention as proxies for inferring the level of polymorphism at MHC loci (Ammer et al, 1992;Ellegren et al, 1993;Schwaiger et al, 1993Schwaiger et al, , 1994. The analysis of variation at these loci has produced contrasting results.…”

Section: Introductionmentioning

confidence: 99%

Selection on MHC-linked microsatellite loci in sheep populations

et al. 2007

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Microsatellites within the major histocompatibility complex (MHC) region have received increasing attention as proxy measures of the level of polymorphism at the Mhc genes themselves. We assessed the diversity of microsatellite loci within or in close proximity of the Mhc genes in several breeds of domestic sheep (Ovis aries) and the wild Mouflon (Ovis orientalis musimon). This was compared to variation at other microsatellite loci scattered throughout the sheep genome. Significantly higher number of alleles were observed at the MHC microsatellites. The sheep breeds studied fell into high-and low-diversity group. This grouping is not related to the agricultural use of the breeds, whether for milk, meat or wool. It is, however, correlated with the geographic origins of the breeds. Southern breeds are genetically more diverse than northern breeds. The observed heterozygosity was in most cases lower than Hardy-Weinberg expectations. The potential impact of selective breeding by man on this is discussed. Neutrality tests indicated that for most of the breeds, the distribution of alleles at the MHC-linked microsatellites are more even than would be expected if the genes were neutral and sampled from populations under driftmutation equilibrium. Hitchhiking due to tight linkage with alleles at the MHC loci that are under balancing selection is proposed as a possible explanation for this pattern.

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Typing of artiodactyl MHC‐DRB genes with the help of intronic simple repeated DNA sequences

Cited by 55 publications

References 8 publications

Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.)

Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population (Ovis aries L.)

No evidence for major histocompatibility complex–dependent mating patterns in a free–living ruminant population

Selection on MHC-linked microsatellite loci in sheep populations

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