The viral genetic content of the human genome is more variable than we | Mobile DNA

Title: Variation in proviral content among human genomes mediated by LTR recombination
Journal:
Jainy Thomas, Hervé Perron and Cédric Feschotte
Published: 2018/12/18
Digital Identification Number: 10.10 1186/s13100-018-0142-3
Original Link:WeChat Link: Part of
's human DNA actually comes from viruses, many of which were inserted into the original genetic material of human ancestors millions of years ago and have been inherited by future generations since. As a result, it is thought that these substances have not changed much in the modern human genome. Human endogenetive retrovirus (HERV) is by far the most common viral derived sequence in the human genome. A
published in the Journal of Human Rights shows a mechanism that introduces more individual differences in HERV levels from person to person than previously expected.part of human DNA is derived from viruses, many of which were inserted into the original genetic material of human ancestors millions of years ago and have been inherited by offspring. Human endogenetive retrovirus (HERV) is by far the most common viral derived sequence in the human genome. Most HERV sequences have long been assotured and therefore coexist among all individuals in the population. However, not all HERV sequences are so, and a small number of HERV sequences have been found to exist only in some individuals. Most of these unseeded HERV components are known to come from relatively recent insertion events, which are still separate in the population. But a
recently published in the Journal of Human Rights suggests that another mechanism has introduced more individual differences in HERV levels from person to person than previously expected. Why is this so?
, it is important to consider the structural characteristics of HERV. In order to be integrated into the host chromosome, these sequences must be full-length elements called pre-viruses. Each pre-virus surrounds the central nuclear tissue, which contains a virus-coded gene sandwiched between long-chain non-coding sequences that repeat at each end, called long-end repetition sequences (LTRs) (see Figure 1). After integration, the two LTRs of the former virus (the same at insertion) are frequently recombined to form the so-called solo LTR. Internal virus genes and one of the two LTRs are eliminated during recombination, leaving a single LTR. It has previously been estimated that 90% of HERV in the human genome is a single LTR, and only 10% maintain its pre-viral form. But what if some of these pre-virus elements are still being transformed into a single LTR? Researchers at the University of Utah and Cornell University looked at the problem and assessed the extent to which the LTR recombination process produced HERV mutations in humans.
Jainy Thomas has developed a new computational method that allows them to screen large numbers of DNA sequences from different populations to detect possible rare LTR recombination events. Given the large number of HERV sequences in the human genome, the task is like looking for a needle in a haystack. The researchers looked at three variants of the retrovirus family from a public data set of 130 genome-wide sequences of 130 different genetic groups supported by the Simons Foundation: HERV-K (HML2), HERV-W, and HERV-H. The method developed by Dr Thomas allows it to find most of the HERV variants previously registered and to find more variants (Figure 2). Not surprisingly, most of the newly discovered variants are apparently very rare because they are found only in one or more individuals. But it is also surprising because many of these HERVs have long been inserted into the DNA of their human ancestors, and some have even been shared with relatives of the most recent apes, and are therefore considered to be fixed in the human population. Nevertheless, Dr. Thomas was able to test the validity of her calculations by experimentally proving that several of these variants were indeed isolated in the population.
it important to consider this type of HERV variant? There are many reasons to believe that these genetic variants may be a neglected source of human physiological variation that leads to disease susceptibleness. In fact, there is growing evidence that the three HERV families surveyed in the study played a beneficial and pathogenic role in humans. For example, HERV-coded genes are expressed in individuals with diseases such as amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease), multiple sclerosis, and some cancers, and their genetic products are thought to be related to the cause or progression of these diseases. On the other hand, some HERVs seem to have useful features. A recent study by Dr. Feschotte and colleagues showed that some HERVs are essential for proper regulation of the body's immune response. The former viral HERV-H component is one of the sources of variation revealed in a newly published study on Mobile DNA and has been shown to be important for maintaining the erraticity of embryonic cells (i.e., the ability to differentiate into different cell types). Therefore, it will be important to better quantify the presence or absence of these pre-viral HERV viruses in individuals and groups to better understand how these components affect human health and physiological function.
Human endogenous retroviruses (HERVs) occupy a substantial fraction of the genome and impact cellular function with both beneficial and deleterious consequences. The vast majority of HERV sequences descend from ancient retroviral families no longer capable of infection or genomic propagation. In fact, most are no longer represented by full-length proviruses but by solitary long terminal repeats (solo LTRs) that arose via non-allelic recombination events between the two LTRs of a proviral insertion. Because LTR-LTR recombination events may occur long after proviral insertion but are challenging to detect in resequencing data, we hypothesize that this mechanism is a source of genomic variation in the human population that remains vastly underestimated.We developed a computational pipeline specifically designed to capture dimorphic proviral/solo HERV allelic variants from short-read genome sequencing data. When applied to 279 individuals sequenced as part of the Simons Genome Diversity Project, the pipeline retrieves most of the dimorphic loci previously reported for the HERV-K(HML2) subfamily as well as dozens of additional candidates, including members of the HERV-H and HERV-W families previously involved in human development and disease. We experimentally validate several of these newly discovered dimorphisms, including the first reported instance of an unfixed HERV-W provirus and an HERV-H locus driving a transcript (ESRG) implicated in the maintenance of embryonic stem cell pluripotency.Our findings indicate that human proviral content exhibit more extensive interindividual variation than previously recognized, which has important bearings for deciphering the contribution of HERVs to human physiology and disease. Because LTR retroelements and LTR recombination are ubiquitous in eukaryotes, our computational pipeline should facilitate the mapping of this type of genomic variation for a wide range of organisms.

is an open access, peer-reviewed journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
(Source: Science.com)