Comparative genomic analysis of warthog and Sus scrofa identifies adaptive genes associated with African swine fever

Background: As warthogs (Phacochoerus africanus) have innate immunity against African swine fever (ASF), it is critical to understand the evolutionary novelty of warthogs to explain their specific ASF resistance. Methods: Here, we present two completed new genomes of one warthog and one Kenyan domestic pig as fundamental genomic references to elucidate the genetic mechanisms of ASF tolerance. Results: Multiple genomic variations, including gene losses, independent contraction, and the expansion of specific gene families, likely molded the warthog genome to adapt to the environment. Importantly, the analysis of the presence and absence of genomic sequences revealed that the DNA sequence of the warthog genome had an absence of the gene lactate dehydrogenase B (LDHB) on chromosome 2 compared with the reference genome. The overexpression and siRNA of LDHB inhibited the replication of the African swine fever virus. Combined with large-scale sequencing data from 42 pigs worldwide, the contraction and expansion of tripartite motif-containing (TRIM) gene families revealed that TRIM family genes in the warthog genome are potentially responsible for its tolerance to ASF. Conclusion: Our results will help improve the understanding of genetic resistance to ASF in pigs.