Different Host-Endogenous Retrovirus Relationships between Mammals and Birds Reflected in Genome-Wide Evolutionary Interaction Patterns.

Mammals and birds differ largely in their average endogenous retrovirus loads, namely the proportion of endogenous retrovirus in the genome. The host-endogenous retrovirus relationships, including conflict and co-option, have been hypothesized among the causes of this difference. However, there has not been studies about the genomic evolutionary signal of constant host-endogenous retrovirus interactions in a long-term scale and how such interactions could lead to the endogenous retrovirus load difference. Through a phylogeny-controlled correlation analysis on ∼5,000 genes between the dN/dS ratio of each gene and the load of endogenous retrovirus in 12 mammals and 21 birds, separately, we detected genes that may have evolved in association with endogenous retrovirus loads. Birds have a higher proportion of genes with strong correlation between dN/dS and the endogenous retrovirus load than mammals. Strong evidence of association is found between the dN/dS of the coding gene for leucine-rich repeat-containing protein 23 and endogenous retrovirus load in birds. Gene set enrichment analysis shows that gene silencing rather than immunity and DNA recombination may have a larger contribution to the association between dN/dS and the endogenous retrovirus load for both mammals and birds. The above results together showing different evolutionary patterns between bird and mammal genes can partially explain the apparently lower endogenous retrovirus loads of birds, while gene silencing may be a universal mechanism that plays a remarkable role in the evolutionary interaction between the host and endogenous retrovirus. In summary, our study presents signals that the host genes might have driven or responded to endogenous retrovirus load changes in long-term evolution.