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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.
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Selection for translation efficiency on synonymous polymorphisms in recent human evolution.

Yedael Y Waldman1, Tamir Tuller, Alon Keinan

  • 1Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.

Genome Biology and Evolution
|August 2, 2011
PubMed
Summary
This summary is machine-generated.

Synonymous mutations are not always silent. Natural selection acts on translation efficiency (TE), influencing human evolution and potentially impacting disease associations. This study reveals selection pressures on TE across human populations.

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Area of Science:

  • Human Evolution
  • Population Genetics
  • Molecular Biology

Background:

  • Synonymous mutations, previously considered neutral, can alter protein translation efficiency (TE).
  • The extent to which TE influences natural selection in human evolution remains largely unexplored.
  • Understanding TE's role is crucial for interpreting genetic variations and disease associations.

Purpose of the Study:

  • To conduct the first genome-wide investigation of natural selection acting on TE in recent human evolution.
  • To analyze the impact of synonymous single nucleotide polymorphisms (SNPs) on TE and allele frequencies across diverse human populations.
  • To determine the correlation between TE-altering SNPs and selective pressures (positive and negative).

Main Methods:

  • Genome-wide survey of 13,798 synonymous SNPs in 1,198 individuals from 11 human populations.
  • Analysis of allele frequency differentiation between populations to infer selection.
  • Correlation analysis between SNP effects on TE and observed selection patterns.

Main Results:

  • Evidence for both negative and positive natural selection acting on TE in human populations.
  • The magnitude of an SNP's effect on TE correlates with its likelihood of being under selection.
  • Negative selection is more pronounced in highly expressed genes, complex proteins, and regulatory genes.
  • Positive selection is stronger for SNPs with large TE effects in lowly interacting proteins and regulatory genes.
  • Essential genes show enrichment for negative TE selection and underrepresentation for positive TE selection.

Conclusions:

  • Translation efficiency (TE) is a significant selective force in recent human evolution.
  • Silent SNPs, due to their impact on TE, are important for understanding human genetic variation and disease.
  • Two synonymous SNPs with potential clinical implications in phenylketonuria and Best's macular dystrophy were identified due to TE differences.