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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Gene Evolution - Fast or Slow?02:05

Gene Evolution - Fast or Slow?

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...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
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Adaptive cis-regulatory changes may involve few mutations.

Pablo Razeto-Barry1, Karin Maldonado

  • 1Instituto de Filosofía y Ciencias de la Complejidad, Los Alerces 3024, Santiago, Chile.

Evolution; International Journal of Organic Evolution
|October 26, 2011
PubMed
Summary

Cis-regulatory regions may be as important as protein-coding regions for genetic adaptation. Despite fewer mutations, regulatory changes can have a larger adaptive impact due to reduced pleiotropy.

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Area of Science:

  • Evolutionary developmental biology (evo-devo)
  • Genetics
  • Molecular evolution

Background:

  • A key debate in evo-devo concerns the roles of protein-coding and cis-regulatory regions in adaptation.
  • Recent studies suggest cis-regulatory regions are less important due to fewer substitutions driving phenotypic variation.

Purpose of the Study:

  • To re-evaluate the relative importance of cis-regulatory versus protein-coding regions in evolutionary adaptation.
  • To explore the impact of substitution 'size' and pleiotropy on adaptive contributions.

Main Methods:

  • Theoretical analysis using geometrical reasoning.
  • Comparative analysis of substitution numbers and their potential adaptive effects.

Main Results:

  • The number of substitutions is not the sole determinant of adaptive contribution.
  • Cis-regulatory substitutions may have larger average adaptive effects than protein-coding substitutions due to lower pleiotropy.

Conclusions:

  • Cis-regulatory regions might contribute equally or more to adaptation than protein-coding regions, despite a lower number of adaptive mutations.
  • The functional impact (adaptive contribution) of mutations is crucial for understanding evolutionary adaptation.