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Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor beta (TGFbeta) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance.
Heterozygote, Polymorphism, Genetic, Sheep, Science, Q, R, Growth Differentiation Factor 9, Environment, Fertility, Gene Frequency, Pregnancy, Transforming Growth Factor beta, Mutation, Hybrid Vigor, Medicine, Animals, Female, Bone Morphogenetic Protein 15, Crosses, Genetic, Research Article
Heterozygote, Polymorphism, Genetic, Sheep, Science, Q, R, Growth Differentiation Factor 9, Environment, Fertility, Gene Frequency, Pregnancy, Transforming Growth Factor beta, Mutation, Hybrid Vigor, Medicine, Animals, Female, Bone Morphogenetic Protein 15, Crosses, Genetic, Research Article
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 75 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |