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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
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Recoverability of ancestral recombination graph topologies.

Elizabeth Hayman1, Anastasia Ignatieva2, Jotun Hein3

  • 1Department of Mathematics, University of Oxford, Andrew Wiles Building, Oxford OX2 6GG, UK.

Theoretical Population Biology
|August 6, 2023
PubMed
Summary

Reconstructing evolutionary histories with recombination is difficult. For SARS-CoV-2, accurately inferring ancestral recombination graphs (ARGs) from genetic data is challenging, limiting our understanding of viral evolution.

Keywords:
Ancestral recombination graphCoalescentGene conversionRecombination detection

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Area of Science:

  • Evolutionary biology
  • Population genetics
  • Bioinformatics

Background:

  • Recombination is a key driver of genetic diversity in populations.
  • Accurate reconstruction of ancestral recombination graphs (ARGs) from sequencing data is crucial for understanding evolutionary processes.
  • Challenges arise from accurately assigning mutations to lineages and ordering coalescent events.

Purpose of the Study:

  • To investigate the probability of reconstructing true ARG topologies under models of recombination and gene conversion.
  • To explore the impact of sample size and mutation rate on ARG reconstruction uncertainty.
  • To assess the theoretical limitations of ARG reconstruction methods.

Main Methods:

  • Theoretical investigation of ARG reconstruction probabilities under the coalescent with recombination and gene conversion.
  • Analysis of how sample size and mutation rate influence ARG reconstruction accuracy.
  • Application of findings to evolutionary rate estimates for various organisms, including SARS-CoV-2.

Main Results:

  • The study quantifies the inherent uncertainty in reconstructed ARGs.
  • It highlights the significant challenges in accurately inferring evolutionary histories when recombination is present.
  • For SARS-CoV-2, realistic parameter values indicate a low probability of reconstructing accurate genealogies.

Conclusions:

  • Reconstructing accurate ancestral recombination graphs (ARGs) is theoretically challenging, particularly with high recombination rates.
  • Sample size and mutation rate are critical factors influencing the accuracy of ARG inference.
  • Current methods may struggle to reconstruct true evolutionary histories for rapidly evolving viruses like SARS-CoV-2.