Mining livestock genomes for a One Health perspective in the management of animal genetic resources

Viruses constantly and silently circulate, emerge and re-emerge in human and animal populations causing mild to severe diseases. Some examples are derived by coronaviruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV-1) and the recently emerged SARS-CoV-2, the Bovine coronavirus (BCoV) the Porcine Epidemic Diarrhea Virus (PEDV) and the Middle-East respiratory syndrome coronavirus (MERS-CoV). Several animal species can act as reservoirs of these viruses that have already demonstrated the ability to easily cross species barriers. This suggests that in livestock and companion animals, within-species genetic variability determining susceptibility or resistance to viral infections should be evaluated as part of a global One Health perspective to reduce the risk that these infecting agents may pose for animal and human populations. In addressing this challenging objective, we investigated the genetic variability of hundreds of candidate genes of the host genomes that can serve as receptors for priming the infection of viruses or are involved in the subsequent progress of the viral diseases, including the well-known ACE2, ANPEP, DPP4 and TMPRSS2 involved in the progression of coronavirus infections. For this purpose, we mined a few thousand of sequenced genomes of four main livestock species (Bos taurus, Sus scrofa, Gallus gallus and Oryctolagus cuniculus), retrieved from public sequence repositories or obtained from newly generated datasets. We then in silico modelled the relevance of the identified DNA variants in conferring potential differences in susceptibility to viral diseases, considering a comparative analysis with the homologous human gene and protein structure. At the inferred protein level, some of the detected within-species mutations in the host genes are expected to modify the virus-host interaction dynamics that could alter the response of the host to the infections. Overall, the obtained results can be useful to establish risk evaluation systems in a One Health approach that includes within-species genetic diversity as potential risk factors to be considered in selection and conservation programs of animal genetic resources.