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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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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...
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Cis-regulatory Sequences02:02

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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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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...
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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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Gene Evolution - Fast or Slow?02:05

Gene Evolution - Fast or Slow?

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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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Related Experiment Video

Updated: Apr 17, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

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Long-term evolution of regulatory DNA sequences. Part 2: theory and future challenges.

Elia Mascolo1, Réka Borbély1, Noa O Borst2

  • 1Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg AT-3400, Austria.

Current Opinion in Genetics & Development
|April 15, 2026
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Summary

This study explores the evolution of cis-regulatory elements (CREs) using genotype-phenotype maps. It reviews evolutionary concepts to understand CREs

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Systems Biology

Background:

  • Cis-regulatory elements (CREs), including promoters and enhancers, control gene expression by binding transcription factors (TFs).
  • Decades of research have produced models of TF-DNA interactions and their combined effects on gene regulation.

Purpose of the Study:

  • To synthesize insights into a quantitative genotype-phenotype (GP) map for gene regulation, enabling simulations of CRE evolution.
  • To explore fundamental questions regarding the de novo evolution of CREs, the diversity of regulatory functions, and factors influencing CRE evolvability.

Main Methods:

  • Review of evolutionary concepts such as epistasis, robustness, evolvability, tunability, plasticity, and bet-hedging applied to gene regulatory sequences.
  • Evaluation of the potential for a unifying theory for the evolution of regulatory sequences.

Main Results:

  • The synthesis of TF-DNA interaction models into a global GP map offers a powerful tool for studying regulatory sequence evolution.
  • Application of evolutionary concepts provides a framework for understanding the dynamics and constraints of CRE evolution.

Conclusions:

  • A unifying theory for regulatory sequence evolution is potentially achievable by integrating biophysical models with evolutionary principles.
  • Key open challenges remain in fully understanding and predicting the evolutionary trajectories of gene regulatory sequences.