Abstract As warthog ( Phacochoerus africanus ) has innate immunity against African swine fever (ASF), it is critical to understand the evolutionary novelty of warthog to explain its specific ASF resistance. Here, we present two completed new genomes of one warthog and one Kenyan domestic pig, as the fundamental genomic references to decode the genetic mechanism on ASF tolerance. Our results indicated, multiple genomic variations, including gene losses, independent contraction and expansion of specific gene families, likely moulded warthog’s genome to adapt the environment. Importantly, the analysis of the presence and absence of genomic sequences revealed that, the warthog genome had a DNA sequence absence of the lactate dehydrogenase B (LDHB) gene on chromosome 2 compared to the reference genome. The overexpression and siRNA of LDHB indicated that its inhibition on the replication of ASFV. Combining with large-scale sequencing data of 123 pigs from all over the world, contraction and expansion of TRIM genes families revealed that TRIM family genes in the warthog genome were potentially responsible for its tolerance to ASF. Our results will help further improve the understanding of genetic resistance ASF in pigs.

Genome Assemblies of the Warthog and Kenyan Domestic Pig Provide Insights into Suidae Evolution and Candidate Genes for African Swine Fever Tolerance