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Related Concept Videos

Synteny and Evolution02:31

Synteny and Evolution

John H. Renwick first coined the term “synteny” in 1971, which refers to the genes present on the same chromosomes, even if they are not genetically linked. The species with common ancestry tend to show conserved syntenic regions. Therefore, the concept of synteny is nowadays used to describe the evolutionary relationship between species.
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Multi-species Conserved Sequences

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Exon Recombination02:32

Exon Recombination

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Gene Duplication and Divergence

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The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
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Increased constraints on MC4R during primate and human evolution.

David A Hughes1, Anke Hinney, Harald Brumm

  • 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. hughes@eva.mpg.de

Human Genetics
|November 18, 2008
PubMed
Summary
This summary is machine-generated.

Human melanocortin 4 receptor (MC4R) shows low genetic diversity, suggesting deleterious mutations, unlike chimpanzees. This conserved gene evolved under strong purifying selection, impacting human obesity research.

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Area of Science:

  • Evolutionary biology
  • Genetics
  • Human obesity research

Background:

  • Melanocortin 4 receptor (MC4R) mutations are a leading genetic cause of human obesity.
  • The evolutionary history of the MC4R locus is largely unknown.
  • Understanding MC4R evolution can inform obesity research.

Purpose of the Study:

  • Investigate patterns of genetic variation at MC4R in humans and chimpanzees.
  • Analyze the evolutionary conservation and selection pressures on MC4R across vertebrates.
  • Determine if functional mutations in MC4R occur at evolutionarily constrained sites.

Main Methods:

  • Resequencing MC4R in 1,015 humans from 51 populations and 8 chimpanzees.
  • Molecular evolutionary analyses including 12 primate species and 29 additional vertebrates.
  • Comparative genomic analysis of MC4R coding regions.

Main Results:

  • Significantly lower genetic diversity at MC4R in humans compared to chimpanzees.
  • MC4R is highly conserved across vertebrates, with purifying selection increasing threefold during primate evolution.
  • Non-synonymous mutations impacting MC4R function preferentially occur at highly conserved sites.

Conclusions:

  • Low human MC4R diversity suggests transient deleterious mutations may contribute to obesity.
  • Strong purifying selection on MC4R throughout vertebrate evolution, particularly in primates, highlights its functional importance.
  • Evolutionary analysis of MC4R provides insights into its role in human obesity and identifies critical functional sites.