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Genetics and the understanding of selection

Key Points

  • Genetics is important to our understanding of selection for at least three reasons: first, although the concept of selection seems obvious, it was not until selection was linked to Mendelian genetics that it became a viable explanation for evolution; second, linkage, non-Mendelian inheritance and relatedness add more complex dimensions to selection and allow the spread of deleterious alleles; and third, the apparent failure of selectionist models to explain genetic observations, such as levels of polymorphism, led to the development of alternative models of evolution and sophisticated statistical methods for the diagnosis of the modes of evolution.

  • Debate remains regarding the values of the selectionist and nearly neutral theories. The proportion of substitutions that result from selection is currently unresolved. Selection is expected to have limits, but what this means in practice is still emerging. For example, recent evidence indicates that synonymous mutations and gene-order rearrangements are both subject to selection in mammals. In the genomic age, discovery-led application of statistical methods for identifying genomic domains under selection — for example, scans for selective sweeps — is a growing area of research. Genome scans can identify candidate regions that might be undergoing selection, but identifying how and why selection acts, if at all, will require integration of molecular biology and molecular evolution. Understanding selection at a molecular level is important to discover how genomes work and for the optimization and risk management of genetic interventions.

Abstract

At first sight selection is a simple notion, and some consider it the most important evolutionary force. But how important is selection, is it really so trivial to understand and what are the alternatives? Here I discuss how genetics is crucial for addressing all of these questions: genetics allowed the concept of natural selection to become viable, it contributed to our understanding of the complexities of selection and it spurred the development of competing models of evolution. Understanding how and why selection acts has important potential applications, from understanding the mechanisms of disease and microbial resistance, to improving the design of transgenes and drugs.

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Figure 1: Heterozygosity predicted by the neutral hypothesis.
Figure 2: Effective population size and fixation in the nearly neutral model.

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Acknowledgements

The author is a Royal Society Wolfson Research Merit Award holder.

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Glossary

Synonymous mutation

A nucleotide change in an exonic DNA sequence that does not result in a change in the encoded amino acid. A synonymous mutation that reaches fixation becomes a synonymous substitution.

Hardy–Weinberg ratio

The binomial distribution of genotypes in a population, such that frequencies of the genotypes AA, Aa and aa will be p2, 2pq and q2, respectively, in which p is the frequency of allele A and q is the frequency of allele a.

Evolutionary stable strategy theory

An approach to mathematically modelling evolution that defines equilibrium positions as positions at which, if all individuals are using the same strategy, invasion by rare individuals who adopt a different strategy is impossible.

Optimality theory

A quantitative evolutionary model that defines the maximum or minimum fitness values for a given trait under specified constraints. It is often used to investigate life-history evolution.

Linkage disequilibrium

A measure of genetic associations between alleles at different loci that indicates whether certain allelic combinations are more or less common than expected.

Haplotype block

A chromosomal region in which groups of alleles at different genetic loci are inherited together more often than expected by chance.

Pseudoautosomal region

Any section on a telomeric end of an X or Y chromosome that undergoes recombination in the heterogametic (XY) sex.

Meiotic drive

A distortion of meiotic inheritance such that one allele at a heterozygous site is recovered in more than half of the gametes (in contrast to the expected 50:50 Mendelian segregation) owing to effects that occur before zygote formation.

Cytoplasmic factor

A gene present in host organelles, such as mitochondria, or in intracellular parasites, such as Wolbachia, that is typically passed from mother to offspring through the cytoplasm.

Cytoplasmic sex-ratio distorter

A factor inherited in the cytoplasm (for example, mitochondria or heritable bacteria) that modifies the sex ratio, typically causing a female bias.

Cytoplasmic incompatibility

A sperm–egg incompatibility that is usually associated with Wolbachia infection. Wolbachia modify the host sperm in the testes, and the same strain of Wolbachia must be present in the egg to rescue this modification. Absence of rescue results in incompatibility and zygotic lethality.

T complex

A region on chromosome 17 in the mouse that is subject to meiotic drive. The complex contains four inversions and occupies approximately half of the chromosome.

Kin selection

Selection that allows an individual to increase its fitness by increasing the number of copies of its genes in the population by provisioning benefits to relatives.

Modern synthesis

The prevailing theoretical framework of evolution that resulted from a combination of genetics, systematics, comparative morphology and palaeontology in the 1930s and 1940s. It is also known as evolutionary synthesis or the synthetic theory.

Effective population size

(Ne). The size of a population measured by the expected effect (through genetic drift) of the population size on genetic variability. It is related to, but never exceeds, the true population size (N).

Poisson distribution

A discrete frequency distribution of the number of independent events per time interval, for which the mean value is equal to the variance.

Dispersion

The ratio of the variance to the mean rate of evolution observed when orthologous sequences from at least three different taxa are compared.

Exonic splice enhancer

A short (approximately 6 nucleotide) motif that is present in exons. It is necessary for the binding of serine–arginine proteins that are involved in defining exon ends.

Isochore

A chromosomal block of approximately uniform GC nucleotide content. This is shown, for example, by a correlation in nucleotide content between genes when comparing introns and synonymous sites.

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Hurst, L. Genetics and the understanding of selection. Nat Rev Genet 10, 83–93 (2009). https://doi.org/10.1038/nrg2506

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