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Related Concept Videos

Epistasis Analysis01:09

Epistasis Analysis

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Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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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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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Higher-order epistasis within Pol II trigger loop haplotypes.

Bingbing Duan1, Chenxi Qiu2, Steve W Lockless3

  • 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260.

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|January 31, 2024
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Summary
This summary is machine-generated.

RNA polymerase II's trigger loop (TL) shows species-specific incompatibilities, revealing complex genetic interactions. These findings illuminate how residue interactions drive the evolution of this essential transcription machinery.

Keywords:
deep mutational scanningepistasishaplotypestrigger loop

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • RNA polymerase II (Pol II) is crucial for transcription, with a conserved trigger loop (TL) domain regulating fidelity and speed.
  • Previous studies explored pairwise genetic interactions within and around the TL to understand residue function.
  • Widespread incompatibility was observed between TLs from different species within the *Saccharomyces cerevisiae* Pol II context.

Purpose of the Study:

  • To investigate the reasons behind species-specific TL sequence incompatibilities with *S. cerevisiae* Pol II.
  • To dissect higher-order genetic interactions within multiply substituted TLs.
  • To understand the role of epistasis in the evolution of the TL domain.

Main Methods:

  • Analysis of pairwise genetic interactions between TL residues and surrounding regions.
  • Construction and analysis of multiply substituted TLs in the *S. cerevisiae* Pol II system.
  • Identification and classification of epistatic patterns arising from complex residue interactions.

Main Results:

  • Identified widespread incompatibility between heterologous TLs and *S. cerevisiae* Pol II, indicating species-specific epistasis.
  • Revealed both positive and negative higher-order residue interactions within TL haplotypes.
  • Demonstrated that complex epistasis is sometimes only apparent from intermediate genotypes.

Conclusions:

  • Complex, higher-order epistasis involving TL residues plays a significant role in Pol II function and evolution.
  • Specific TL residues exhibit distinct epistatic patterns, potentially guiding TL domain evolution.
  • Epistatic interactions provide mechanistic insights into how Pol II evolves.