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Viral Mutations00:36

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Virus-derived variation in diverse human genomes.

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New computational tools reveal previously overlooked virus-derived structural variants (SVs) in human genomes. These findings enhance our understanding of virus-host coevolution and ongoing gene transfer, contributing to human genetic diversity.

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Area of Science:

  • Genomics
  • Virology
  • Human Genetics

Background:

  • Viral genetic material acquisition by hosts can create structural genome variation.
  • Previous studies have cataloged structural variants (SVs) but may have missed virus-derived ones.

Purpose of the Study:

  • To develop computational tools for identifying virus-derived SVs in population-scale whole genome sequencing (WGS) data.
  • To apply these tools to a cohort of 3,332 humans to uncover novel virus-derived SVs.

Main Methods:

  • Development and application of novel computational tools for SV detection in WGS datasets.
  • Analysis of 3,332 human WGS samples to identify virus-derived SVs.
  • Utilizing linkage disequilibrium to map previously uncharacterized HERV-K loci.

Main Results:

  • Detection of non-germline SVs from squirrel monkey retrovirus (SMRV), human immunodeficiency virus 1 (HIV-1), and human T lymphotropic virus (HTLV-1) in cell lines.
  • Identification of novel heritable SVs from human herpesvirus 6 (HHV-6) and human endogenous retrovirus-K (HERV-K).
  • Characterization of the first solo-direct repeat (DR) HHV-6 and discovery of novel polymorphic HERV-K loci linked to traits.

Conclusions:

  • The developed tools successfully identified overlooked virus-derived SVs, including both non-germline and heritable variants.
  • These findings expand the understanding of virus-human coevolution and ongoing viral gene transfer as a source of human genetic variation.
  • Identified variants have implications for gene expression studies and experimental biosafety.