Viral DNA accounts for 1.3% of the human genome, study finds

Surprisingly, not all the useful DNA in your chromosomes comes from your evolutionary ancestors – some of it was borrowed from elsewhere. Your DNA includes the genes from at least eight retroviruses. These are a kind of virus that makes use of the cell’s mechanisms for coding DNA to take over a cell. At some point in human history, these genes became incorporated into human DNA. These viral genes in DNA now perform important functions in human reproduction, yet they are entirely alien to our genetic ancestry.

Study Name:Endogenous retroviruses in the human genome sequence


The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes. Can the draft human genome sequences help us to define the role of these elements more closely?

One of the many striking findings to come from the sequencing of the human genome is that some 45% of our DNA is composed of transposable elements such as LINE and Alu retroelements and DNA transposons [,,]. Around 8% of the genome is derived from sequences with similarity to infectious retroviruses, which can be easily recognized because all infectious retroviruses contain at least three genes, including gag (encoding structural proteins), pol (viral enzymes), and env (surface envelope proteins), as well as long terminal repeats (LTRs; see Figure Figure1).1). The existence of human endogenous retroviruses (HERVs) has been known for many years [], but their abundance in the genome was not predicted by earlier studies. HERVs represent the remnants of ancestral retroviral infections that became fixed in the germline DNA. Subsequent retrotransposition events amplified these sequences to a high load within the genome. The drafts of the human genome have provided a wealth of information about the abundance and distribution of HERVs, and several new subtypes have been identified []. This sequence information can now be used for the design of novel experimental strategies to investigate the biological functions of HERVs. This article briefly reviews the evolution and abundance of HERVs and the available evidence for their function in both normal and pathological processes.

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Structure of retroviral proviruses. (a) Infectious retroviruses have at least three genes: gag, which encodes the structural proteins of the viral core; pol, which encodes the viral enzymes, including reverse transcriptase; and env, which encodes the surface glycoproteins of the viral envelope. Viral protein expression is controlled by promoter and enhancer elements and polyadenylation signals in the long terminal repeats (LTRs), which are generated during reverse transcription. Other regulatory elements are also present in the viral genome, including splice donor (SD) and acceptor (SA) sites (for env expression) and a primer-binding site (PBS) for a specific tRNA molecule used to initiate reverse transcription. The tRNA specificity varies among different retroviruses and has been used to classify endogenous retroviruses in the human genome. (b) Human endogenous retroviruses (HERVs) have a similar structure to the proviruses of infectious retroviruses but typically contain many inactivating mutations including point mutations (dark bands), frameshifts and deletions (particularly in env). Frequently, the entire central portion has been lost by homologous recombination, leaving behind a ‘solitary LTR’. Although almost all HERVs are defective, the LTRs may still be active, and transcription of HERVs is common particularly in fetal tissue and in inflammatory disease and cancer. In a few cases, coding competence has been retained for env even when adjacent viral genes are heavily mutated, suggesting that selective pressures have maintained these open reading frames because they serve a cellular function.

HERVs have been grouped into three broad classes – I, II and III – on the basis of sequence similarity to different genera of infectious retroviruses. Each class has a number of subgroups, many of which are named according to an older system of HERV nomenclature based on the specificity of the tRNA primer-binding site (Figure (Figure1).1). Class I HERVs are related to gammaretroviruses such as murine leukemia virus (MLV); class I includes HERV-W and HERV-H, among many other subgroups. Class II HERVs are related to betaretroviruses such as mouse mammary tumor virus and include several types of HERV-K element. Class III HERVs are distantly related to spumaretroviruses and include HERV-L and HERV-S.

Like other transposable elements, HERVs are thought to have played an important role in the evolution of mammalian genomes, and the human genome sequence has already been of use in phylogenetic studies of HERVs. By analyzing HERV integration sites, the evolution of these elements has been tracked through the primate lineage. Measurement of the divergence of LTR sequences has also been used as a ‘molecular clock’ to estimate the age of HERVs (given that the LTRs are identical at the time of integration) []. Class I and class III HERVs are the oldest groups and are present throughout the primate lineage, while class II includes HERVs that have been active most recently. Many class II loci are restricted to chimpanzees and humans and a few proviruses of the HERV-K(HLM-2) subgroup are human-specific [], indicating that these viruses have been active within the last 5 million years.

Viral DNA accounts for 1.3% of the human genome, study finds

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Written by ceciliagerson1