Comprehensive identification and characterization of HERV-K (HML-9) group in the human genome

Background: Human endogenous retroviruses (HERVs) result from ancestral infections by exogenous retroviruses that became incorporated into germ-line DNA and evolutionary fixed in the human genome. HERVs could vertically transmit in a Mendelian fashion and stable maintenance in the human genome which are estimated to comprise about 8%. HERV-K (HML1-10) transcription has been confirmed to be associated with a variety of diseases, such as breast cancer, lung cancer, prostate cancer, melanoma, rheumatoid arthritis, and amyotrophic lateral sclerosis. However, the poorly characterization of HML-9 hinders a detailed understanding of the expression regulation of this family in human health and its actual impact on host genomes. In the light of this, the definition of a precise and updated HERV-K HML-9 genomic map is urgently needed. Results: We report a comprehensive analysis of HERV-K HML-9 sequences presence and distribution within the human genome, with a detailed description of the different structural and phylogenetic aspects characterizing the group. A total of 23 proviruses and 47 solo LTR elements were characterized with a detailed description of provirus structure, integration time, potentially regulated genes, transcription factor binding sites, and primer binding site features. The integration time results showed that the HML-9 elements found in the human genome have been integrated into the primate lineage between 37.5 and 151.5 million years ago (mya). Conclusion: The results have finally clarified the composition of HML-9, providing an exhaustive background for subsequent functional studies.