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Multifactorial genetics

Understanding quantitative genetic variation

Key Points

  • High levels of inherited variation are observed for most traits and in most populations. Variation is maintained partly by mutation and partly by a balance of selective forces; however, we do not know the relative importance of these alternatives.

  • This variation allows a rapid response to natural and artificial selection. Newly arising mutations make an important contribution to long-term selection response. Selection response in large experimental populations often continues steadily for many generations, indicating that many genetic loci are involved.

  • Understanding the maintenance of variation, and the response to selection, requires that the sequence changes that cause trait differences be identified. This is challenging, because variation might depend on multiple alleles that include several interacting sites.

  • Population genetics makes predictions about the nature of quantitative trait loci (QTL). For example, balancing selection is expected to maintain alleles at high frequency, whereas mutation is likely to maintain rare alleles.

  • Predictions for the way that alleles interact, and for the size of their effects, depend on assumptions about the relationship between genotype and phenotype. One simple model indicates that QTL effects should be exponentially distributed.

Abstract

Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL) — the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability.

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Figure 1: Examples of long-term selection response.
Figure 2: Alternative genetic models for long-term selection response.
Figure 3: Adaptation in the Fisher/Orr model.

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Acknowledgements

We are grateful to the Biotechnology and Biological Sciences Research Council and the Royal Society for their support, and to W. Hill, T. Mackay, M. Slatkin, M. Turelli, B. Walsh and an anonymous referee for their helpful comments on the manuscript.

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Correspondence to Nicholas H. Barton.

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DATABASES

LocusLink 

α-globin

β-globin

achaete-scute

Adh

Delta

hairy

scabrous 

MaizeDB 

tb1

tga1

ENCYCLOPEDIA OF LIFE SCIENCES

Quantitative genetics

Glossary

QUANTITATIVE TRAIT LOCI

(QTL). Genetic loci identified through the statistical analysis of complex traits (such as plant height or body weight). These traits are typically affected by more than one gene and also by the environment.

HERITABILITY

The fraction of the phenotypic variance due to additive genetic variance (VA/VP).

ENVIRONMENTAL VARIANCE

The variance in the trait among genetically identical individuals. This variation might be due to the different environmental conditions experienced by different individuals, or to essentially random factors.

GENETIC VARIANCE

The variance of trait values that can be ascribed to genetic differences between individuals.

STABILIZING SELECTION

Intermediate phenotypes have greater fitness than extreme phenotypes.

DIRECTIONAL SELECTION

Natural selection that acts to promote the fixation of a particular allele.

DISRUPTIVE SELECTION

Intermediate phenotypes have lower fitness than extreme phenotypes; the opposite of stabilizing selection.

INFINITESIMAL MODEL

A simple model of the inheritance of quantitative traits, which assumes an infinite number of unlinked loci, each with an infinitesimal effect.

EFFECTIVE POPULATION SIZE

The size of the ideal population in which the effects of random drift would be the same as observed in the actual population.

LINKAGE DISEQUILIBRIUM

The condition in which the frequency of a particular haplotype is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

SELECTIVE SWEEP

After the fixation of a new favourable mutation, the surrounding region of the genome is also fixed; neutral diversity is therefore 'swept' out of the population.

BALANCER CHROMOSOME

Chromosome with recessive lethal mutations and inverted segments that suppress recombination.

BALANCING SELECTION

Selection that acts to maintain two or more alleles in a population.

OVERDOMINANCE

The phenotype of the heterozygote is greater than that of either homozygote. Overdominance for fitness can lead to the maintenance of both alleles in the population.

DOMINANCE

A genetic interaction between the two alleles at a locus, such that the phenotype of heterozygotes deviates from the average of the two homozygotes.

EPISTASIS

In the context of quantitative genetics, epistasis refers to any genetic interaction in which the combined phenotypic effect of two or more loci is less than (negative epistasis) or greater than (positive epistasis) the sum of effects at individual loci.

DIRECTIONAL DOMINANCE

The phenotype of individuals that are heterozygous for the multiple loci that affect a trait deviates from the average of the phenotypes of homozygous individuals.

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Barton, N., Keightley, P. Understanding quantitative genetic variation. Nat Rev Genet 3, 11–21 (2002). https://doi.org/10.1038/nrg700

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