Comparative Genomic Analysis of Warthog and Sus Scrofa Identifies Adaptive Genes Associated with African Swine Fever

SIMPLE SUMMARY: This study aimed to elucidate the evolution of African Suidae and the molecular basis of their unique phenotypes, thereby attempting to fill these gaps. To this end, we performed the genome assembly and annotation of warthogs and Kenyan domestic pigs to identify the genetic resources responsible for warthog resistance against African swine fever. Our results showed that genes in the warthog genome relate to its adaptation to the African environment and that the gene lactate dehydrogenase B could be considered a tolerance gene to African swine fever. We believe that our study makes a significant contribution to the literature because our results provide valuable resources and data support for future evolutionary research on African pigs and genetic research adapted to unique local geographic environments in Africa. Additionally, the results of this study provide a new candidate gene for understanding the resistance mechanisms of warthogs against African swine fever. ABSTRACT: 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.