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Related Concept Videos

Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
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...
Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

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 DNA...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
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...

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Mosaic Zebrafish Transgenesis for Evaluating Enhancer Sequences
07:23

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Published on: July 17, 2010

Highly conserved non-coding sequences are associated with vertebrate development.

Adam Woolfe1, Martin Goodson, Debbie K Goode

  • 1Medical Research Council Rosalind Franklin Centre for Genomics Research Hinxton, Cambridge, United Kingdom.

Plos Biology
|January 5, 2005
PubMed
Summary
This summary is machine-generated.

Researchers identified nearly 1,400 highly conserved non-coding sequences in vertebrates by comparing human and pufferfish genomes. These sequences, crucial for developmental gene regulation, show significant enhancer activity in zebrafish embryos.

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Area of Science:

  • Genomics
  • Developmental Biology
  • Comparative Genomics

Background:

  • The human genome contains substantial regulatory DNA, challenging to identify using computational or functional methods.
  • Comparative sequence analysis, comparing genomic regions across species, helps identify functionally constrained DNA.
  • High sequence similarity between divergent species often indicates functional importance.

Purpose of the Study:

  • To identify highly conserved non-coding sequences (HCNSS) across vertebrates using whole-genome comparison.
  • To investigate the potential role of HCNSS in regulating developmental genes.
  • To functionally test identified HCNSS using a rapid in vivo assay.

Main Methods:

  • Whole-genome comparison between human and pufferfish (Fugu rubripes) to detect conserved non-coding sequences.
  • Bioinformatic analysis to identify nearly 1,400 HCNSS, predominantly near developmental regulator genes.
  • In vivo enhancer activity assay using zebrafish embryos to test functional significance of selected HCNSS.

Main Results:

  • Identified ~1,400 HCNSS, many showing >90% identity over 500+ bases between humans and Fugu, exceeding coding sequence conservation.
  • HCNSS were primarily located near genes involved in developmental regulation, including transcription factors.
  • Functional testing in zebrafish revealed that 23 out of 25 tested HCNSS exhibited significant tissue-specific enhancer activity.

Conclusions:

  • A set of vertebrate-specific HCNSS has been identified, clustered around key developmental genes.
  • These HCNSS likely constitute essential components of the regulatory network controlling vertebrate development.
  • The findings highlight the utility of comparative genomics and rapid in vivo assays for discovering and functionally validating regulatory elements.