Abstract
BackgroundAbout half of the human genome is constituted of transposable elements, including human endogenous retroviruses (HERV). HERV sequences represent the 8% of our genetic material, deriving from exogenous infections occurred millions of years ago in the germ line cells and being inherited by the offspring in a Mendelian fashion. HERV-K elements (classified as HML1–10) are among the most studied HERV groups, especially due to their possible correlation with human diseases. In particular, the HML10 group was reported to be upregulated in persistent HIV-1 infected cells as well as in tumor cells and samples, and proposed to have a role in the control of host genes expression. An individual HERV-K(HML10) member within the major histocompatibility complex C4 gene has even been studied for its possible contribution to type 1 diabetes susceptibility. Following a first characterization of the HML10 group at the genomic level, performed with the innovative software RetroTector, we have characterized in detail the 8 previously identified HML10 sequences present in the human genome, and an additional HML10 partial provirus in chromosome 1p22.2 that is reported here for the first time.ResultsUsing a combined approach based on RetroTector software and a traditional Genome Browser Blat search, we identified a novel HERV-K(HML10) sequence in addition to the eight previously reported in the human genome GRCh37/hg19 assembly. We fully characterized the nine HML10 sequences at the genomic level, including their classification in two types based on both structural and phylogenetic characteristics, a detailed analysis of each HML10 nucleotide sequence, the first description of the presence of an Env Rec domain in the type II HML10, the estimated time of integration of individual members and the comparative map of the HML10 proviruses in non-human primates.ConclusionsWe performed an unambiguous and exhaustive analysis of the nine HML10 sequences present in GRCh37/hg19 assembly, useful to increase the knowledge of the group’s contribution to the human genome and laying the foundation for a better understanding of the potential physiological effects and the tentative correlation of these sequences with human pathogenesis.
Highlights
About half of the human genome is constituted of transposable elements, including human endogenous retroviruses (HERV)
Localization and characterization of HERV-K(HML10) sequences Following the report of a duplicated HML10 integration in the fourth component of human complement gene (C4) genes [32], in our previous analysis performed through the bioinformatics tool RetroTector software (ReTe), a total of eight HML10 sequences were identified, seven of which were reported for the first time [3] (Table 1)
Seven of these were used in a subsequent study that did not include the HML10 provirus in locus 19p13.2 [27], possibly relying on its misleading annotation by RepeatMasker. 19p13.2 HML10 provirus, is ~550 nucleotides shorter as compared to the relative annotation in Genome Browser, which improperly associated to this HML10 locus an additional 5′ portion that is albeit not part of the HML10 proviral structure, being instead an HML9 Long Terminal Repeats (LTR) (LTR14C) that probably belongs to a surrounding HML9 proviral sequence
Summary
About half of the human genome is constituted of transposable elements, including human endogenous retroviruses (HERV). The main examples are Syncytin-1 and -2, two Env proteins encoded by a HERV-W [4, 5] and a HERV-FRD provirus [6], respectively, providing essential fusogenic and immunosuppressive functions to human placenta [6,7,8,9] To explain their persistence in the human genome, it has been proposed that HERVs could be neutral sequences, not negatively selected and removed during evolution (parasitic theory), or, they could be involved in important cellular functions leading to their positive selection over time (symbiotic theory) [10]. MHC is the genome region being associated with more disorders than any other one, especially concerning autoimmune and infectious diseases [20]
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