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Related Concept Videos

Viral Mutations00:36

Viral Mutations

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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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Gene Evolution - Fast or Slow?02:05

Gene Evolution - Fast or Slow?

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The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
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Limits to Natural Selection01:38

Limits to Natural Selection

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Organisms that are well-adapted to their environment are more likely to survive and reproduce. However, natural selection does not lead to perfectly adapted organisms. Several factors constrain natural selection.
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Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

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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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Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

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Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
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Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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Is SARS-CoV-2 facing constraints in its adaptive evolution?

Yingguang Liu1

  • 1Department of Biomedical Sciences, College of Osteopathic Medicine, Liberty University, Lynchburg, Virginia, the United States of America.

Biomolecules & Biomedicine
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adaptation has slowed, with mutations offering less benefit. Recent Omicron variants show reduced replication and milder COVID-19 outcomes, despite high infection rates.

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Area of Science:

  • Virology
  • Evolutionary Biology
  • Epidemiology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has demonstrated remarkable adaptation to the human population over five years.
  • Key adaptations include enhanced receptor binding via spike (S) protein mutations and upper respiratory tract colonization, shortening incubation periods and increasing spread.
  • Immune evasion mutations have emerged, sometimes at the cost of replicative fitness, driving variant evolution.

Purpose of the Study:

  • To analyze the evolutionary trajectory of SARS-CoV-2.
  • To investigate the impact of mutations on viral fitness, transmission, and pathogenicity.
  • To understand the limits of viral adaptation and predict future trends.

Main Methods:

  • Analysis of viral genetic sequences to identify mutations and track evolutionary changes.
  • Assessment of receptor binding affinity and replicative fitness in vitro.
  • Evaluation of immune escape properties and pathogenicity in animal models and human populations.

Main Results:

  • SARS-CoV-2 adaptation, particularly in S protein receptor binding, appears to have plateaued around late 2023/early 2024.
  • Purifying selection is now dominant in Omicron lineages, with diminishing fitness benefits from missense mutations.
  • Omicron subvariants exhibit reduced replication efficiency in cell cultures and attenuated pathogenicity in animal models compared to earlier strains.
  • The codon adaptation index has decreased in Omicron subvariants, indicating reduced efficiency of synonymous mutations.

Conclusions:

  • The evolutionary capacity of SARS-CoV-2 may be reaching functional limits, with a shift towards purifying selection.
  • Recent Omicron variants demonstrate reduced viral fitness and pathogenicity, correlating with declining COVID-19 mortality despite sustained high infection rates.
  • Future SARS-CoV-2 evolution may involve trade-offs between immune evasion and replicative capacity, potentially leading to less severe disease outcomes.