Measuring immunogenetic diversity during the Pleistocene

• Applicant: Professor Dr. Alex Greenwood, Ph.D.
• Subject Area: Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions ; Evolution, Anthropology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256739398

The vast majority of genetic diversity studies focus on currently existing populations. However, population genetic studies incorporating ancient DNA have demonstrated for many species that current diversity and diversity distribution does not reflect even the recent past. To date, almost all population genetic analysis using ancient DNA has relied on mitochondrial DNA analysis and on measuring diversity and its distribution over time. We propose to investigate nuclear DNA diversity in two species from the late Pleistocene through the Holocene (an approximate 60,000 year time span) for the nuclear DNA diversity of immunologically important nuclear DNA loci. The major contrast between the chosen species is that one, the woolly mammoth (Mammuthus primigenius) is extinct and the muskoxen (Ovibos moschatus) survived the end Pleistocene extinctions approximately 10,000 years ago which saw the disappearance of most of the Eurasian and American megafaunal (> 30 kg) species. The loci of interest are in the major histocompatibility complex (MHC) and Toll-Like-Receptor genes (TLRs) representing the adaptive and innate immune systems respectively. Diversity in these genes is crucial to host defence against pathogens. Variation in MHC diversity correlates with factors such as parasite load and resistance to viral infection. TLR diversity evolution is generally less well characterized in non-primates but like MHC diversity, is associated with variation in resistance to infectious disease. Reduced diversity in both the innate and adaptive immune genes is associated with susceptibility to pathogens which if taken to extremes could hypothetically result in species declines. The woolly mammoth and the muskox are two of the best characterized species for mitochondrial DNA diversity with hundreds of samples analyzed. We propose to characterize MHC and TLR diversity in mammoths and muskoxen previously characterized for mitochondrial diversity to examine changes over space and time. The data set obtained will represent the first long term evolutionary analysis of immunogenetic diversity in the context of known mitochondrial diversity for two of the largest collections of ancient DNA available. We expect to determine the rate of evolution, persistence and replacement of TLR and MHC alleles for both species which will provide a better understanding of the evolutionary dynamics of the loci that cannot be obtained from examination of modern DNA. Given that muskoxen and mammoths both share demographic patterns at given time points and diverge at others, the comparison will provide context for elucidating general principles of immunogenetic evolution e.g. demonstrate whether similar demographic changes elicit similar evolutionary immnogenetic trends.

• DFG Programme: Research Grants
• International Connection: Canada, Denmark
• Participating Persons: Dr. Paula Campos; Dr. Camila Mazzoni, Ph.D.; Professor Dr. Hendrik Poinar