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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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Epistasis01:39

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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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The Concept of Multiple Allelism
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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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Single Nucleotide Polymorphisms-SNPs01:05

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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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Updated: Jun 9, 2025

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
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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, USA.

Genetics
|October 24, 2024
PubMed
Summary
This summary is machine-generated.

RNA polymerase II's trigger loop (TL) controls transcription. Incompatible species-specific TL interactions reveal complex genetic epistasis, offering insights into how this crucial protein domain evolves.

Keywords:
deep mutational scanningepistasishaplotypestrigger loop

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • RNA polymerase II (Pol II) is essential for gene transcription.
  • The conserved trigger loop (TL) domain of Pol II regulates transcription fidelity and speed.
  • Previous studies explored pairwise genetic interactions within and around the TL.

Purpose of the Study:

  • To understand functional residue interactions within the Pol II TL.
  • To investigate how individual mutations affect TL function.
  • To dissect the nature of higher-order genetic interactions within multiply substituted TLs.

Main Methods:

  • Analysis of pairwise genetic interactions between TL residues.
  • Construction and testing of multiply substituted TLs in Saccharomyces cerevisiae Pol II.
  • Examination of epistasis between TL residues and the broader Pol II protein.

Main Results:

  • Identified widespread incompatibility between heterologous species' TLs within the S. cerevisiae Pol II context.
  • Revealed complex, higher-order epistasis among TL residues, including both positive and negative interactions.
  • Demonstrated that some epistatic patterns are only apparent from intermediate genotypes.

Conclusions:

  • Species-specific interactions within the Pol II TL and its surroundings are critical.
  • Higher-order epistasis plays a significant role in shaping TL function and evolution.
  • Specific TL residues exhibit distinct epistatic patterns, potentially guiding TL evolution.