Divergent Allele Advantage provides a quantitative model for maintaining alleles with a wide range of intrinsic merits

Stefan, T., Matthews, L. , Prada, J. M., Mair, C., Reeve, R. and Stear, M. J. (2019) Divergent Allele Advantage provides a quantitative model for maintaining alleles with a wide range of intrinsic merits. Genetics, 212(2), pp. 553-564. (doi:10.1534/genetics.119.302022) (PMID:30952668) (PMCID:PMC6553829)

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Abstract

The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. However, both theoretical results and simulation models have shown that overdominance in its classical form cannot maintain large numbers of alleles unless all alleles confer unrealistically similar levels of fitness. There is increasing evidence that heterozygotes containing genetically divergent alleles allow for broader antigen presentation to immune cells, providing a selective mechanism for MHC polymorphism. By framing competing models of overdominance within a general framework, we show that a model based on Divergent Allele Advantage (DAA) provides a superior mechanism for maintaining alleles with a wide range of intrinsic merits, as intrinsically less fit MHC alleles that are more divergent can survive under DAA. Specifically, our results demonstrate that a quantitative mechanism built from the Divergent Allele Advantage hypothesis is able to maintain polymorphism in the MHC. Applying such a model to both livestock breeding and conservation could provide a better way of identifying superior heterozygotes and quantifying the advantages of genetic diversity at the MHC.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mair, Dr Colette and Stefan, Mr Thorsten and Reeve, Dr Richard and Stear, Professor Mike and Matthews, Professor Louise and Prada Jimenez de Cisneros, Dr Joaquin
Authors: Stefan, T., Matthews, L., Prada, J. M., Mair, C., Reeve, R., and Stear, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Science and Engineering > School of Mathematics and Statistics > Statistics
Journal Name:Genetics
Publisher:Genetics Society of America
ISSN:0016-6731
ISSN (Online):1943-2631
Published Online:05 April 2019

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
468351The effect of selection for nematode resistance on mhc class II diversiityMichael StearBiotechnology and Biological Sciences Research Council (BBSRC)BB/F015313/1III - PARASITOLOGY
629831The influence of selective breeding on MHC diversityLouise MatthewsBiotechnology and Biological Sciences Research Council (BBSRC)BB/L004070/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED
730011Mathematical Theory and Biological Applications of DiversityRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/P004202/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED
569671Ecological and socioeconomic factors impacting maintenance and dissemination of antibiotic resistance in the Greater Serengeti EcosystemLouise MatthewsBiotechnology and Biological Sciences Research Council (BBSRC)BB/K01126X/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED