Human Alu elements promote the establishment and enhancement of piRNA-protein-coding gene targeting relationships

Abstract

Abstract Background: PIWI-interacting RNAs (piRNAs) are the most diverse category of small RNAs in animals. Recent evidence suggests that transposable elements (TEs) incorporated into protein-coding genes (PCGs) can be targeted by piRNAs. Thus, TEs might have a piRNA-mediated influence on organisms. In human PCGs, the extent to which TEs contribute to the presence of piRNA target sites remains to be assessed. Moreover, related evolutionary forces remain to be explored. Results: We found that the presence of Alu elements, a class of primate-specific TEs, in human PCGs almost always results in potential piRNA target sites. Additionally, we observed that Alu elements can exert a secondary influence on piRNAs and their potential target sites via interlocus gene conversion (IGC). This mutagenic process can homogenize piRNAs and their potential target sites, resulting in an excess of single nucleotide variants (SNVs) that increase piRNA-PCG targeting affinity in the genome. Although Aluelements facilitate the occurrence of SNVs that increase piRNA-PCG targeting affinity, these SNVs tend to show low allele frequencies in the human population. This footprint suggests that natural selection opposes the promotion effect of Alu elements on the formation of piRNA-PCG targeting relationships. Conclusions: Human Alu elements promote both the establishment and enhancement of piRNA-PCG targeting relationships. In addition, piRNA-PCG targeting relationships impose a piRNA-related selective constraint on the evolution of human PCGs. Our work suggests that the interplay between Alu elements and piRNAs is an important factor that influences the evolutionary trajectory of human PCGs.