BBSRC EASTBIO DTP - Developing African buffalo genomics as a tool to understand bovid resistance to African diseases

The African buffalo (Syncerus caffer) is the most closely related African wild bovid to the domestic cow (Bos taurus). Buffalo are infected by all of the most important African cattle pathogens (e.g. trypanosomes, Theileria parva, foot and mouth disease virus, Mycobacteria bovis), but generally do not suffer the serious clinical disease seen in cattle; most likely due to prolonged co-evolution with pathogens selecting for disease control. By contrast, archaeological evidence suggests that cattle were only introduced into Africa within the last 8,000 years and many of the cattle populations used in current agricultural systems have been introduced much more recently. The African buffalo therefore represents a uniquely valuable model in terms of understanding bovine control of infectious disease. Knowledge of how buffalo are able to control infections with these pathogens and the genetic basis of such resistance could be exploitable for devising methods to control the corresponding infections in cattle, either through enhancement of immune responses or by genetic means. The latter is particularly timely with the advent of gene editing technologies, which have opened up new opportunities to modify genes in domestic species based on data from resistant wildlife species. However, there is no reference genome to enable the qualitative analysis of the genetic basis behind important traits, and comparisons with other relevant genomes (e.g. B. taurus and the Asian buffalo Bubalus bubalis).

To provide the foundation for the downstream characterisation of the biological mechanisms underlying African buffalo resistance to cattle pathogens, we will generate the first African buffalo reference genome using a combination of Pacbio and Illumina sequencing data. Following the assembly of the genome using a hybrid assembly approach we will then determine the regions of the genome showing evidence of positive selection, i.e. candidate regions potentially associated with adaptation to the local African environment. This will be achieved by first comparing the genome to that of its closest ancestor, the Asian Buffalo (B. bubalis), to identify regions linked to putative selective sweeps using gene-based (e.g. dN/dS) and relative-rate methods. By sequencing 150 genomes (Illumina) from across Africa (Tanzania, Kenya, Uganda and South Africa) we will also assess population genomic diversity and the locations of population-specific selective sweeps. Using B. taurus as an outgroup to assign ancestral and derived states to alleles, we will combine these inter-species and population diversity data to identify species specific regions of accelerated evolution. Together these will provide a comprehensive picture of the locations of putative adaptive selective sweeps in the African buffalo genome, providing a shortlist of candidate genomic regions linked to local environmental adaptation.

The student will gain training in bioinformatics, population and evolutionary genetics. There will also be opportunities to undertake wet lab work resulting in a cross-disciplinary set of abilities that will provide a highly competitive foundation for a future career in science. This project is in collaboration with colleagues in Africa and there will therefore also be potential to travel to Kenya during the course of the PhD.