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Related Experiment Videos

Positive and negative selection on the human genome.

J C Fay1, G J Wyckoff, C I Wu

  • 1Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA.

Genetics
|July 17, 2001
PubMed
Summary

Most DNA mutations are harmful, but a small fraction are neutral or slightly deleterious. A significant portion of protein evolution is driven by positive selection, shaping species differences.

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Area of Science:

  • Molecular Evolution
  • Population Genetics
  • Genomics

Background:

  • Distinguishing between deleterious, neutral, and adaptive mutations is crucial for understanding molecular evolution.
  • Estimating the proportion of DNA variation that is deleterious and the fraction of fixed differences driven by positive selection is a key challenge.
  • Human genetic data, including polymorphism and divergence, offer a valuable resource for these estimations.

Purpose of the Study:

  • To estimate the fraction of neutral, deleterious, and adaptive mutations in the human genome.
  • To quantify the proportion of slightly deleterious mutations and their frequency in natural populations.
  • To assess the role of positive Darwinian selection in driving protein divergence between species.

Main Methods:

  • Analysis of human polymorphism and divergence data for a large number of genes.
  • Estimation of neutral mutations using the ratio of common amino acid (A) to synonymous (S) single nucleotide polymorphisms (SNPs) at specific frequencies.
  • Quantification of deleterious and slightly deleterious mutations based on their frequencies in populations.

Main Results:

  • The fraction of neutral amino acid mutations is estimated to be approximately 0.20.
  • Around 80% of amino acid mutations are deleterious, with at least 20% being slightly deleterious and common.
  • Slightly deleterious mutations constitute at least 3% of amino acid SNPs per individual (approx. 300 per diploid genome).
  • The ratio of fixed differences (A/S) between species is higher than that of common SNPs, indicating a substantial role for positive selection in protein evolution.

Conclusions:

  • A significant portion of genetic variation is composed of slightly deleterious mutations.
  • Positive Darwinian selection plays a major role in driving adaptive protein divergence between human and other species.
  • These findings provide insights into the evolutionary forces shaping genetic diversity and species differences.

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