Elucidating the relationship between heterozygosity and fitness in a natural vertebrate population

• Applicant: Professor Dr. Joseph Hoffman
• Subject Area: Sensory and Behavioural Biology ; Evolution, Anthropology ; Evolutionary Cell and Developmental Biology (Zoology) ; Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243472732

Many important fitness traits including parasite resistance, survivorship and reproductive success often correlate with heterozygosity in natural populations. Where documented, such heterozygosity fitness correlations (HFCs) have the potential to influence interactions between pathogens and their hosts and the evolution of mate choice. However, because most studies use only around ten microsatellite markers, we do not yet know which of two possible mechanisms is most important nor the types of gene involved. Fortunately, Next Generation Sequencing technologies allow the development of gene-targeted Single Nucleotide Polymorphisms (SNPs) which, if screened in a species where high-quality fitness measures can be gathered, should for the first time allow direct links to be made between fitness and the heterozygosity of literally thousands of genes. I will exploit just such a system, the Antarctic fur seal (Arctocephalus gazella), in which an exceptionally detailed long term study has already revealed HFCs for numerous traits.By screening 6000 SNPs in 1500 female seals for which detailed fitness data are available, I will distinguish between two primary hypotheses proposed to explain HFCs. Under the general effects hypothesis, HFCs are ascribed to inbreeding depression, with marker heterozygosity providing a surrogate measure of an individual inbreeding coefficient f. Here, additional markers should improve the estimate of f and the relationship between fitness and average marker heterozygosity will strengthen. Under the alternative local effect model, which invokes chance linkage between individual markers and genes experiencing balancing selection, heterozygosity is uncorrelated among loci such that more markers will if anything reduce HFC strength as the contribution of any one marker becomes progressively diluted.In practice, local effects are likely to be present even if inbreeding depression is involved, but as with the primary mechanism these are poorly understood. For example, are the underlying genes diverse or mostly related to immunity or growth? To explore these and related questions, SNPs targeted within specific classes of genes identified by comparison with the dog genome will be analysed individually and as haplotypes for associations with fitness. Local effects will then be fine-mapped, by constructing the first marine mammal linkage map and through comparative genomics with the dog, to determine which genomic regions are involved and what specific genes they contain. The resulting dataset of over 9000000 SNP genotypes will thereby provide an unprecedented window on how genetic variability impacts key fitness traits in a natural mammalian population.

• DFG Programme: Research Grants
• International Connection: Sweden, United Kingdom
• Participating Persons: Jaume Forcada, Ph.D.; Professor Dr. Jon Slate; Professor Dr. Fritz Trillmich; Professor Dr. Jochen B. W. Wolf