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  • Review Article
  • Published:

Which evolutionary processes influence natural genetic variation for phenotypic traits?

Nature Reviews Genetics volume 8, pages 845–856 (2007)Cite this article

Key Points

  • We have little understanding about the evolutionary forces that influence the genes underlying complex-trait variation.

  • Genome-wide association studies and analyses of amino-acid polymorphisms are advancing rapidly, but have yet to elucidate the selective importance of QTL alleles.

  • Positive selection, local adaptation, balancing selection and deleterious mutations all contribute to phenotypic trait variation, but their relative importance is unknown.

  • Understanding the genetic architecture of complex traits is essential for interpreting the evolutionary significance of phenotypic variation. The frequency and magnitude of QTL alleles can help us to distinguish between balancing selection or mutation–selection balance. This will require fine mapping (and ultimately cloning) of QTLs in multiple or complex mapping populations.

  • In evolutionary studies of humans, laboratory organisms and ecological model species, similarities in the approaches used and the questions asked are more important than differences among species.

Abstract

Although many studies provide examples of evolutionary processes such as adaptive evolution, balancing selection, deleterious variation and genetic drift, the relative importance of these selective and stochastic processes for phenotypic variation within and among populations is unclear. Theoretical and empirical studies from humans as well as natural animal and plant populations have made progress in examining the role of these evolutionary forces within species. Tentative generalizations about evolutionary processes across species are beginning to emerge, as well as contrasting patterns that characterize different groups of organisms. Furthermore, recent technical advances now allow the combination of ecological measurements of selection in natural environments with population genetic analysis of cloned QTLs, promising advances in identifying the evolutionary processes that influence natural genetic variation.

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Figure 1: The fitness effects of alleles differ between environments.
Figure 2: Colour polymorphism in Linanthus parryae.
Figure 3: Molecular basis of local adaptation to oxygen availability in deer mice.
Figure 4: Molecular basis of local variation in the coat colour of beach mice.

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Acknowledgements

We thank D. Lowry, A. Manzaneda, J. Modliszewski, M. Rausher, C. Wu and three anonymous reviewers for helpful comments and discussion. We are grateful to P. Bierzychudek and D. Schemske for unpublished photos of Linanthus parryae, and to H. Hoekstra and J. Storz for permission to reprint figures from their publications. This work was supported by the US National Science Foundation, US National Institutes of Health and Duke University, Durham, USA.

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  1. Department of Biology, BOX 90338, Duke University, Durham, 27708, North Carolina, USA

    Thomas Mitchell-Olds & John H. Willis

  2. Center for Population Genomics and Pharmacogenetics, Duke Institute for Genomic Sciences and Policy, Duke University Medical Center, BOX 3471, Duke University,

    David B. Goldstein

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  1. Thomas Mitchell-Olds
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  2. John H. Willis
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Correspondence to Thomas Mitchell-Olds.

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Glossary

Mutation–selection balance

Models that examine equilibrium levels of genetic variation attributable to mutation, natural selection and genetic drift.

Balancing selection

Historically, balancing selection refers to evolutionary processes such as frequency-dependent selection or heterozygote advantage that maintain greater than neutral levels of polymorphism within a population. In the era of molecular population genetics, the term balancing selection is often applied to loci showing species-wide levels of nucleotide polymorphism that exceed neutral expectation, regardless of ecological mechanism or levels of variation within populations.

Local adaptation

The situation in which genotypes from different populations have higher fitness in their home environments owing to historical natural selection.

Disruptive selection

Occurs when individuals with extreme phenotypes have higher fitness than those with intermediate trait values.

Overdominance

An unusual mode of gene action whereby heterozygotes at a given locus have higher fitness than either homozygote.

Positive selection

Directional selection based on phenotype.

Signatures of selection

Patterns of nucleotide polymorphism, allele frequency and linkage disequilibrium that distinguish selected loci from neutrally evolving genomic regions.

Metapopulations

A series of partially isolated conspecific populations that are subject to local extinction and recolonization.

Selective sweep

Directional selection that fixes an advantageous mutation in a population.

Site frequency spectrum

Statistical tests in population genetics use information on the numbers of SNPs that are rare or common, and the frequency of ancestral and derived alleles in order to infer demographic history and possible natural selection. One widely-used statistic is Tajima's D.

Antagonistic pleiotropy

The situation in which allelic variation at a locus has phenotypic effects on two or more separate traits, or on the same trait expressed in two or more environments.

Clinal variation

A gradual change in trait value or gene frequency across a geographical area.

Admixture

The pattern of genetic variation that results when a population is derived from founders that originated from more than one ancestral population.

Population structure

The distribution of individuals in partially isolated populations. A metapopulation is one example of a population structure, and includes local extinction and recolonization.

Epistasis

Occurs when two or more polymorphic loci interact to determine phenotype.

Frequency-dependent selection

Occurs when rare alleles have higher fitness than common alleles. This process can maintain genetic variation within populations.

Directional selection

This form of selection favours a particular allele because of its effect on phenotype.

Genetic architecture

The number, magnitude and frequencies of QTL alleles, as well as their patterns of epistasis and genotype–environment interaction.

Ascertainment bias

A biased estimation of population genetic parameters when the studied individuals are a non-random sample of a reference population. For example, association studies are biased towards the detection of common polymorphisms.

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Mitchell-Olds, T., Willis, J. & Goldstein, D. Which evolutionary processes influence natural genetic variation for phenotypic traits?. Nat Rev Genet 8, 845–856 (2007). https://doi.org/10.1038/nrg2207

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