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Home / Equine Research Bank / Genome Res / Noncoding sequences conserved in a limited number of mammals...
Genome research2004; 14(3); 367-372; doi: 10.1101/gr.1961204

Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional.

Abstract: Cross-species DNA sequence comparison is a fundamental method for identifying biologically important elements, because functional sequences are evolutionarily conserved, wheres nonfunctional sequences drift. A recent genome-wide comparison of human and mouse DNA discovered over 200,000 conserved noncoding sequences with unknown function. Multispecies DNA comparison has been proposed as a method to prioritize these conserved noncoding sequences for functional analysis based on the hypothesis that elements present in many species are more likely to be functional than elements present in limited numbers of species. Here, we perform a comparative analysis of the single-minded 2 (SIM2) gene interval on human chromosome 21 with horse, cow, pig, dog, cat, and mouse DNA. We classify conserved sequences based on the number of mammals in which they are present, and experimentally test sequences in each class for function. As hypothesized, conserved sequences present in many mammals are frequently functional. Additionally, we demonstrate that sequences conserved in a limited number of mammals are also frequently functional. Examination of genomic deletions in chimpanzee and rhesus macaque DNA showed that several putatively functional conserved noncoding human sequences were absent in these primates. These findings suggest that functional conserved noncoding human sequences can be missing in other mammals, even closely related primate species.
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Publication Date: 2004-02-12 PubMed ID: 14962988PubMed Central: PMC353216DOI: 10.1101/gr.1961204Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The article presents a study that analyses the functionality of noncoding sequences, preserved in a handful of mammals in the SIM2 gene interval on human chromosome 21. The research concludes that these sequences, often thought to be nonfunctional, are frequently functional and that these functional sequences can be missing in other mammals, including closely related primates.

Genome-Wide Comparison

  • The researchers used cross-species DNA sequence comparison, a commonly employed method to identify significant biological elements.
  • The principle of the process is that sequences that serve a purpose are conserved through evolution, whilst those without purpose experience drift and change over time.
  • This approach led to the identification of over 200,000 conserved noncoding sequences with unknown function in a genome-wide comparison between humans and mice.

Prioritization and Validation of CONserved Noncoding Sequences

  • To better understand these sequences, the researchers opted for multispecies DNA comparison. This form of analysis holds that elements found in many species are more likely to be functional than those found in fewer species.
  • The researchers aimed to test this hypothesis by classifying conserved sequences according to the number of mammals they are found in and then testing each class for functionality.
  • The tested conserved sequences were found within the SIM2 gene interval on human chromosome 21, and the comparison involved the DNA of several mammals including horses, cows, pigs, dogs, cats, and mice.

Study Findings and Implications

  • As hypothesized, sequences conserved in many mammals were frequently functional. However, the key result was that sequences conserved in a few mammals were also frequently functional, contrary to prior assumptions.
  • In addition, by examining the genomic deletions in the DNA of chimpanzees and rhesus macaques, it was found that several human sequences that were conserved and thought to be functional were missing.
  • This unexpected finding suggests that conserved noncoding sequences with a function in humans may not be present in other mammals, even those as closely related to humans as primates.

Cite This Article

APA
Frazer KA, Tao H, Osoegawa K, de Jong PJ, Chen X, Doherty MF, Cox DR. (2004). Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional. Genome Res, 14(3), 367-372. https://doi.org/10.1101/gr.1961204

Publication

Genome research
ISSN: 1088-9051
NlmUniqueID: 9518021
Country: United States
Language: English
Volume: 14
Issue: 3
Pages: 367-372

Researcher Affiliations

Frazer, Kelly A
  • Perlegen Sciences, Mountain View, California 95051, USA. Kelly_frazer@perlegen.com
Tao, Heng
    Osoegawa, Kazutoyo
      de Jong, Pieter J
        Chen, Xiyin
          Doherty, Mark F
            Cox, David R

              MeSH Terms

              • Animals
              • Basic Helix-Loop-Helix Transcription Factors
              • Cats
              • Cattle
              • Chromosome Deletion
              • Chromosomes, Artificial, Bacterial / genetics
              • Chromosomes, Human, Pair 21 / genetics
              • Cloning, Molecular
              • Computational Biology / methods
              • Conserved Sequence / genetics
              • Conserved Sequence / physiology
              • DNA, Intergenic / classification
              • DNA, Intergenic / genetics
              • DNA, Intergenic / physiology
              • Dogs
              • Evolution, Molecular
              • Horses / genetics
              • Humans
              • Macaca mulatta / genetics
              • Mice
              • Pan troglodytes / genetics
              • Regulatory Sequences, Nucleic Acid
              • Sequence Homology, Nucleic Acid
              • Swine / genetics
              • Transcription Factors / classification
              • Transcription Factors / genetics
              • Transcription Factors / physiology

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