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  • Review Article
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Molecular spandrels: tests of adaptation at the genetic level

Nature Reviews Genetics volume 12, pages 767–780 (2011)Cite this article

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A Corrigendum to this article was published on 29 November 2011

This article has been updated

Key Points

  • It is now possible to identify genes that underlie fitness-related traits and to detect molecular evidence that they have been affected by natural selection. However, neither of these approaches functionally connects genotype, phenotype and fitness, and thus they do not provide direct evidence that specific alleles are adaptive.

  • Demonstrating that an allele is adaptive requires evidence of the direct effects of alternative alleles on an ecologically relevant phenotype, and hence organismal performance, as well as the effects of these alternative alleles on fitness through known functional mechanisms.

  • Experimental tests of selection on the genes underlying phenotypic traits will help to avoid being led astray by intuitively appealing but potentially incomplete or incorrect adaptive stories ('molecular spandrels').

  • Pioneering studies have used a variety of approaches to isolate the fitness effects of specific alleles from the confounding influence of the surrounding genome, typically by using populations in which the alleles of interest are segregating within either a randomized genetic background or a homogenous genetic background.

  • The use of next-generation sequencing in field experiments represents a promising avenue for carrying out comprehensive tests of adaptation. Incorporating genomics into field experiments should help to: differentiate between the effects of pleiotropy and linkage; characterize the role of epistasis; and allow for fine-scale discrimination of the mechanisms and targets of selection.

Abstract

Although much progress has been made in identifying the genes (and, in rare cases, mutations) that contribute to phenotypic variation, less is known about the effects that these genes have on fitness. Nonetheless, genes are commonly labelled as 'adaptive' if an allele has been shown to affect a phenotype with known or suspected functional importance or if patterns of nucleotide variation at the locus are consistent with positive selection. In these cases, the 'adaptive' designation may be premature and may lead to incorrect conclusions about the relationships between gene function and fitness. Experiments to test targets and agents of natural selection within a genomic context are necessary for identifying the adaptive consequences of individual alleles.

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Figure 1: Connections between various approaches for studying the genetics of adaptation.
Figure 2: Examples of using complementary ecological and molecular approaches to investigate the genetic basis of adaptation.
Figure 3: How understanding genetic architecture can inform us about selection.

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Change history

  • 29 November 2011

    In the above article, Table 1 and Supplementary information S1 (table) incorrectly stated that estimates of selection had not been calculated for the Ace1 gene, a variant of which confers insecticide resistance in mosquitoes. The tables also contained a spelling mistake: the species name Culex pipiens was originally given as Culex pipens in the 'Phenotypic effect' column. The revised tables now include four new papers (listed as references 150 to 153 in the reference list) that discuss the relevant selection studies, and the misspelling of Culex pipiens has been corrected. Additionally, Box 3 contained a typographical error: the time for the carbonaria morph of Biston betularia to reach 98% frequency was 47 years and not 7 years as stated in the Review. The authors apologize for these errors.

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Acknowledgements

We thank P. Andolfatto, A. Berry, J. Jensen, J. Losos, D. Lowry, R. Nielsen, P. Nosil, S. Otto, D. Schluter, J. Slate and M. Szulkin for useful discussion and comments on the manuscript. We thank W. Cresko and P. Hohenlohe for providing a modified figure and L. Cook, J. Mallet and I. Saccheri for providing unpublished data on Biston betularia. We are supported by National Sciences and Research Council of Canada (NSERC) Howard Alper and John Templeton Foundational Questions in Evolutionary Biology (FQEB) fellowships (R.D.H.B.) and a US National Science Foundation (NSF) grant DEB-0919190 (H.E.H.).

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  1. Department of Organismic and Evolutionary Biology, Department of Molecular and Cellular Biology and the Museum of Comparative Zoology, Harvard University, 26 Oxford Street, Cambridge, 02138, Massachusetts, USA

    Rowan D. H. Barrett & Hopi E. Hoekstra

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Supplementary information 1 (table)

Examples of genes commonly described as adaptive. (PDF 206 kb)

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Nature Reviews Genetics series on Study Designs

Glossary

Spandrel

An architectural feature that is necessary in the construction of domed cathedrals, but because of its aesthetic and purposeful design it can easily be confused as the featured element rather than a by-product of an engineering constraint.

Selection coefficient

The strength of selection as measured by the difference in fitness among genotypes.

Directional selection

Natural selection that favours one end of a distribution of a quantitative trait.

Stabilizing selection

Natural selection that favours intermediate values of a quantitative trait.

Disruptive selection

Natural selection that favours extreme values of a quantitative trait over intermediate values.

Neutral theory

This theory holds that standing genetic variation is predominantly neutral, whereas most new mutations are deleterious.

Purifying selection

Natural selection that favours the current condition by removing deleterious alleles that arise in the population.

Nearly neutral theory

An extension of the neutral theory that suggests that polymorphism at functionally important sites is predominantly nearly, rather than completely, neutral.

Effective population sizes

The size of an ideal population of breeding individuals that would experience the same amount of genetic drift as the observed population.

Selective sweeps

The increase in frequency of an allele (and closely linked chromosomal segments) that is caused by positive selection for the allele. Sweeps initially reduce variation and subsequently lead to a local excess of rare alleles (and an excess of homozygosity) as new unique mutations accumulate.

Linkage disequilibrium

(LD). Nonrandom association of alleles at two or more loci. The pattern and extent of linkage disequilibrium in a genomic region is affected by mutation, recombination, genetic drift, natural selection and demographic history.

Fixation index

(FST). A measure of population subdivision, indicating the proportion of genetic diversity found between populations relative to the amount of genetic diversity found within populations.

Ascertainment bias

A consequence of collecting a nonrandom subsample with a systematic bias, so that results based on the subsample are not representative of the entire sample.

Pleiotropic

The effect of a gene on more than one phenotypic trait.

Eumelanic

Consisting of brown to black pigments (that is, eumelanin) found in vertebrate hair, feathers or scales.

Recombinant inbred lines

(RILs). A population of fully homozygous individuals obtained through the repeated self-fertilization of an F1 generation hybrid.

Backcross lines

A population of individuals obtained by crossing a hybrid with one of its parents or to an individual that is genetically similar to its parent in order to generate offspring with genetic identity closer to that of the parent.

Likelihood ratio

The ratio of how many times more likely the observed data are under one model than the other, computed for all pairwise models.

Identical-by-descent lines

A population of individuals sharing identical copies of the same ancestral allele.

Near-isogenic lines

A population of individuals that differs from its parent in only one genomic location, typically a QTL of interest. Using markers that are diagnostic for that QTL, backcrosses are made to the parent until the entire genome of the line is exactly like the parent except in the region around the marker locus.

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Barrett, R., Hoekstra, H. Molecular spandrels: tests of adaptation at the genetic level. Nat Rev Genet 12, 767–780 (2011). https://doi.org/10.1038/nrg3015

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