Retroviruses and Primate Genome Evolution
ABSTRACT Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. HERVs can influence genome regulation through expression of retroviral genes, either via genomic rearrangements following HERV integrations or through the involvement of HERV LTRs in the regulation of gene expression. Some HERVs emerged in the genome over 30 MYr ago, while others have appeared rather recently, at about the time of hominid and ape lineages divergence. HERVs might have conferred antiviral resistance on early human ancestors, thus helping them to survive. Furthermore, newly integrated HERVs could have changed the pattern of gene expression and therefore played a significant role in the evolution and divergence of Hominoidea superfamily. Comparative analysis of HERVs, HERV LTRs, neighboring genes, and their regulatory interplay in the human and ape genomes will help us to understand the possible impact of HERVs on evolution and genome regulation in the primates. BioEssays 22:161-171, 2000.
- SourceAvailable from: PubMed Central
[Show abstract] [Hide abstract]
- "Similarly, as the ERVs in a genome are only derived from a relatively small number of ERV lineages, any replication affinity of particular lineages could, in principle, bias the result. For example, in humans one-third of all ERVs are descended from thirty-one to forty distinct colonizations [3,25]. "
ABSTRACT: We wish to understand how sex and recombination affect endogenous retroviral insertion and deletion. While theory suggests that the risk of ectopic recombination will limit the accumulation of repetitive DNA in areas of high meiotic recombination, the experimental evidence so far has been inconsistent. Under the assumption of neutrality, we examine the genomes of eighteen species of animal in order to compute the ratio of solo-LTRs that derive from insertions occurring down the male germ line as opposed to the female one (male bias). We also extend the simple idea of comparing autosome to allosome in order to predict the ratio of full-length proviruses we would expect to see under conditions of recombination linked deletion or otherwise. Using our model, we predict the ratio of allosomal to autosomal full-length proviruses to lie between 3/2 and 2/3 under increasing male bias in mammals and between 1 and 2 under increasing male bias in birds. In contrast to our expectations, we find that a pattern of male bias is not universal across species and that there is a frequent overabundance of full-length proviruses on the allosome beyond the ratios predicted by our model. We use our data as a whole to argue that full-length proviruses should be treated as deleterious mutations or as effectively neutral mutations whose persistence in a full-length state is linked to the rate of meiotic recombination and whose origin is not universally male biased. These conclusions suggest that retroviral insertions on the allosome may be more prolific and that it might be possible to identify mechanisms of replication that are enhanced in the female sex.BMC Evolutionary Biology 11/2013; 13(1):243. DOI:10.1186/1471-2148-13-243 · 3.41 Impact Factor
[Show abstract] [Hide abstract]
- "Side effects of an HERV-K-specific vaccination can only be studied in humans. Primates encode very similar endogenous retroviral genomes and could be used as a model for safety studies , , , . We showed proof of principle for an HERV-K cancer vaccine in a mouse tumor model. "
ABSTRACT: Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all cells of an individual. They are normally transcriptionally silenced and transmitted only vertically. Enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed in tumor patients and HIV-infected individuals. As HERV-K is usually not expressed and immunological tolerance development is unlikely, it is an appropriate target for the development of immunotherapies. We generated a recombinant vaccinia virus (MVA-HKenv) expressing the HERV-K envelope glycoprotein (ENV), based on the modified vaccinia virus Ankara (MVA), and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) or the HERV-K ENV gene (RLZ-HKenv cells). Intravenous injection of RLZ-HKenv cells into syngenic BALB/c mice led to the formation of pulmonary metastases, which were detectable by X-gal staining. A single vaccination of tumor-bearing mice with MVA-HKenv drastically reduced the number of pulmonary RLZ-HKenv tumor nodules compared to vaccination with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the formation of RLZ-HKenv tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to metastasis. Protection from tumor formation correlated with enhanced HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for the first time that HERV-K ENV is a useful target for vaccine development and might offer new treatment opportunities for diverse types of cancer.PLoS ONE 08/2013; 8(8):e72756. DOI:10.1371/journal.pone.0072756 · 3.23 Impact Factor
[Show abstract] [Hide abstract]
- "Retroelements constitute more than 42% of human DNA and are at present the only class of transs posable elements in mammals capable of transposition (Sverdlov, 2000; Buzdin, 2004). They also play an active role in a multitude of processes of functioning of the human genome (Wessler, 1998; Sverdlov, 1998, 2000; Deininger et al., 2003; Buzdin, 2004). "
ABSTRACT: Mobile elements are DNA fragments that are able to self-replicate within the genome of a host organism. Usually, mobile elements comprise about 40-50% of mammalian genome. In the present review, evolutionary recent insertions of mobile elements are considered which have occurred after divergence of human and chimpanzee ancestral forms, i.e. later than about 6 million years. Human-specific transposable elements are represented by relatively small number of copies that can be subdivided into four groups: HERV-K (HML-2), L1, Alu, and SVA. The number of human-specific copies of HERV-K (HML-2), L1, Alu, and SVA representatives amounts roughly to 150, 1200, 5500, and 860 copies per genome respectively. Furthermore, we succeeded in describing a new family of human-specific mobile elements that are present only in human genome and are absent in other primates. Insertions of human-specific mobile elements can be regarded as important candidates for the role of molecular-genetic agents of anthropogenesis--each new insertion of such a mobile element supplies the acceptor gene locus with the set of new functional sites for binding transcription factors that can make significant alterations to adjacent genes functioning. On the basis of known evidences confirming the influence of human-specific mobile elements on adjacent genes expression, total number of human genes regulated by them can be estimated like hundreds.Zhurnal obshcheĭ biologii 09/2012; 73(1):3-20. DOI:10.1134/S2079086412050027 · 0.12 Impact Factor