Identification and Characterization of the HERV-K (HML-8) Group of Human Endogenous Retroviruses in the Genome

Human endogenous retroviruses (HERVs) can be vertically transmitted in a Mendelian fashion, are stably maintained in the human genome, and are estimated to constitute ∼8% of the genome. HERVs affect human physiology and pathology through their provirus-encoded protein or long terminal repeat (LTR) element effect. Characterization of the genomic distribution is an essential step to understanding the relationships between endogenous retrovirus expression and diseases. However, the poor characterization of human MMTV-like (HML)-8 prevents a detailed understanding of the regulation of the expression of this family in humans and its impact on the host genome. In light of this, the definition of an accurate and updated HERV-K HML-8 genomic map is urgently needed. In this study, we report the results of a comprehensive analysis of HERV-K HML-8 sequence presence and distribution within the human genome and hominoids, with a detailed description of the different structural and phylogenetic aspects characterizing the group. A total of 40 proviruses and 5 solo LTR elements for human were characterized, which included a detailed description of provirus structure, integration time, potentially regulated genes, transcription factor-binding sites, and primer-binding site features. Besides, 9 chimpanzee sequences, 8 gorilla sequences, and 10 orangutan sequences belonging to the HML-8 subgroup were identified. The integration time results showed that the HML-8 elements were integrated into the primate lineage around 35 and 42 million years ago (mya), during primates evolutionary speciation. Overall, the results clarified the composition of the HML-8 groups, providing an exhaustive background for subsequent functional studies.