Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes

Abstract

BackgroundHuman endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies.ResultsIn the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported.ConclusionsThe present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0301-x) contains supplementary material, which is available to authorized users.

Comprehensive Characterization of the Human Endogenous Retrovirus HERV-K(HML-6) Group: Overview of Structure, Phylogeny, and Contribution to the Human Genome

“…In order to better characterize the group, we analyzed the sequences of the PBS; this has been used for the first classification of the group and was expected to be complementary to lysine tRNA, as reported for other HML members (13). Even if, in general, the value of the PBS as a phylogenetic marker is not totally consistent, given the occurrence of alternative PBS types for some HERV groups (30,39), such an analysis corroborated the previous findings for the HML-6 elements (20), confirming that they harbor a type K PBS sequence.…”

“…However, due to deletions and rearrangements, in many instances only one (or none) provirusassociated LTR is available, impairing the estimation of the time of insertion. Hence, we recently implemented the calculation of time of insertion with the use of multiple divergence data between individual genic portions and their consensus (30). Considering a mutation rate in humans of 0,002/nucleotide/million years (31), we estimated the evolutionary age of each HML-6 sequence by calculating nucleotide divergences both between the 5=LTR and 3=LTR of each provirus and between nt 150 to 350 portions of the gag, pol, and env genes and a generated consensus for each subgroup ( Fig.…”

Differential and defective expression of Koala Retrovirus indicate complexity of host and virus evolution

“…We cannot tell from this study whether these transcripts arise from a single genome locus that is identical in all SA animals or multiple loci. Recombination of ERV loci in the genome into new RNA variants in the transcriptome is a well described phenomenon in other species 29,30 and careful comparison of paired DNA and RNA samples from the same animals would be required to untangle this.…”

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

“…Syncytin1 is the envelope protein cytokine of human endogenous retrovirusesW1 (HERVW1), and its coding gene is located on human chromosome 7q21.2, which is a gene trace after HERVW1 infects human germ cells. 6 Human endogenous retroviruses (HERVs) are relics of the infective retrovirus integrated into the human genome, accounting for approximately 5%-8% of the human genome, including at least 31 families. 7 They participate in the regulation of various physiological and pathological activities in humans through different pathways.…”