Polygenic adaptation

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Polygenic adaptation describes a process in which a population adapts through small changes in allele frequencies at hundreds or thousands of loci. [1]

Many traits in humans and other species are highly polygenic, i.e., affected by standing genetic variation at hundreds or thousands of loci. Under normal conditions, the genetic variation underlying such traits is governed by stabilizing selection, in which natural selection acts to hold the population close to an optimal phenotype. However, if the phenotypic optimum changes, then the population can adapt by small directional shifts in allele frequencies spread across all the variants that affect the trait. Polygenic adaptation can occur relatively quickly (as described in the breeder's equation), however it is difficult to detect from genomic data because the changes in allele frequencies at individual loci are very small.

Polygenic adaptation represents an alternative to adaptation by selective sweeps. In classic selective sweep models, a single new mutation sweeps through a population to fixation, purging variation from a region of linkage around the selected site. [2] More recent models have focused on partial sweeps, and on soft sweeps [3] - i.e., sweeps that start from standing variation or comprise multiple sweeping variants at the same locus. All of these models focus on adaptation through genetic changes at a single locus and they generally assume large changes in allele frequencies.

The concept of polygenic adaptation is related to classical models from quantitative genetics. However, traditional models in quantitative genetics usually abstract away the contributions of individual loci by focusing instead on means and variances of genetic scores. In contrast, population genetics models and data analysis have generally emphasized models of adaptation through sweeps at individual loci. The modern formulation of polygenic adaptation in population genetics was developed in a pair of 2010 review articles. [1] [4]

Examples of polygenic adaptation

Polygenic adaptation is presumed to be the dominant mode of adaptation in artificial selection, when plants or animals undergo rapid responses to selective pressures. However, in most cases the actual genetic loci involved are not yet known (but see e.g., [5] ).

At present the best-understood examples of polygenic adaptation are in humans, and particularly for height, a trait that can be interpreted using data from genome-wide association studies. In a 2012 paper, Joel Hirschhorn and colleagues showed that there was a consistent tendency for the "tall" alleles at genome-wide significant loci to be at higher frequencies in northern Europeans than in southern Europeans. [6] They interpreted this observation to indicate that the difference in average height between northern and southern Europeans is at least partly genetic (as opposed to environmental) and that it was driven by selection. This result has been replicated by subsequent studies, [7] [8] [9] [10] however the environmental factor driving the selection remains unclear. A study of recent polygenic adaptation in the English has shown that selection on height has had small effects on allele frequencies (<1%) across most of the genome, and found evidence for polygenic adaptation in a wide variety of other traits as well including selection for increased infant birth size and increased female hip and waist size. [10]

Related Research Articles

An allele, or allelomorph, is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.

Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and population structure.

<span class="mw-page-title-main">Genetic variation</span> Difference in DNA among individuals or populations

Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources of genetic variation, but other mechanisms, such as genetic drift, contribute to it, as well.

A quantitative trait locus (QTL) is a locus that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers correlate with an observed trait. This is often an early step in identifying the actual genes that cause the trait variation.

Genetic architecture is the underlying genetic basis of a phenotypic trait and its variational properties. Phenotypic variation for quantitative traits is, at the most basic level, the result of the segregation of alleles at quantitative trait loci (QTL). Environmental factors and other external influences can also play a role in phenotypic variation. Genetic architecture is a broad term that can be described for any given individual based on information regarding gene and allele number, the distribution of allelic and mutational effects, and patterns of pleiotropy, dominance, and epistasis.

Genetic hitchhiking, also called genetic draft or the hitchhiking effect, is when an allele changes frequency not because it itself is under natural selection, but because it is near another gene that is undergoing a selective sweep and that is on the same DNA chain. When one gene goes through a selective sweep, any other nearby polymorphisms that are in linkage disequilibrium will tend to change their allele frequencies too. Selective sweeps happen when newly appeared mutations are advantageous and increase in frequency. Neutral or even slightly deleterious alleles that happen to be close by on the chromosome 'hitchhike' along with the sweep. In contrast, effects on a neutral locus due to linkage disequilibrium with newly appeared deleterious mutations are called background selection. Both genetic hitchhiking and background selection are stochastic (random) evolutionary forces, like genetic drift.

<span class="mw-page-title-main">Human genetic variation</span> Genetic diversity in human populations

Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism.

In genetics, a selective sweep is the process through which a new beneficial mutation that increases its frequency and becomes fixed in the population leads to the reduction or elimination of genetic variation among nucleotide sequences that are near the mutation. In selective sweep, positive selection causes the new mutation to reach fixation so quickly that linked alleles can "hitchhike" and also become fixed.

<span class="mw-page-title-main">Genome-wide association study</span> Study of genetic variants in different individuals

In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.

<span class="mw-page-title-main">1000 Genomes Project</span> International research effort on genetic variation

The 1000 Genomes Project, launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one thousand anonymous participants from a number of different ethnic groups within the following three years, using newly developed technologies which were faster and less expensive. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature. In 2012, the sequencing of 1092 genomes was announced in a Nature publication. In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research.

Population structure is the presence of a systematic difference in allele frequencies between subpopulations. In a randomly mating population, allele frequencies are expected to be roughly similar between groups. However, mating tends to be non-random to some degree, causing structure to arise. For example, a barrier like a river can separate two groups of the same species and make it difficult for potential mates to cross; if a mutation occurs, over many generations it can spread and become common in one subpopulation while being completely absent in the other.

Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates the extent to which genetic and environmental factors influence individual differences, and the development of research designs that can remove the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans, as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research and in human studies, leading to new scientific discoveries.

In genetics, association mapping, also known as "linkage disequilibrium mapping", is a method of mapping quantitative trait loci (QTLs) that takes advantage of historic linkage disequilibrium to link phenotypes to genotypes, uncovering genetic associations.

Host–parasite coevolution is a special case of coevolution, where a host and a parasite continually adapt to each other. This can create an evolutionary arms race between them. A more benign possibility is of an evolutionary trade-off between transmission and virulence in the parasite, as if it kills its host too quickly, the parasite will not be able to reproduce either. Another theory, the Red Queen hypothesis, proposes that since both host and parasite have to keep on evolving to keep up with each other, and since sexual reproduction continually creates new combinations of genes, parasitism favours sexual reproduction in the host.

The missing heritability problem is the fact that single genetic variations cannot account for much of the heritability of diseases, behaviors, and other phenotypes. This is a problem that has significant implications for medicine, since a person's susceptibility to disease may depend more on the combined effect of all the genes in the background than on the disease genes in the foreground, or the role of genes may have been severely overestimated.

<span class="mw-page-title-main">Polygenic score</span> Numerical score aimed at predicting a trait based on variation in multiple genetic loci

In genetics, a polygenic score (PGS) is a number that summarizes the estimated effect of many genetic variants on an individual's phenotype. The PGS is also called the polygenic index (PGI) or genome-wide score; in the context of disease risk, it is called a polygenic risk score or genetic risk score. The score reflects an individual's estimated genetic predisposition for a given trait and can be used as a predictor for that trait. It gives an estimate of how likely an individual is to have a given trait based only on genetics, without taking environmental factors into account; and it is typically calculated as a weighted sum of trait-associated alleles.

<span class="mw-page-title-main">Complex traits</span>

Complex traits, also known as quantitative traits, are traits that do not behave according to simple Mendelian inheritance laws. More specifically, their inheritance cannot be explained by the genetic segregation of a single gene. Such traits show a continuous range of variation and are influenced by both environmental and genetic factors. Compared to strictly Mendelian traits, complex traits are far more common, and because they can be hugely polygenic, they are studied using statistical techniques such as quantitative genetics and quantitative trait loci (QTL) mapping rather than classical genetics methods. Examples of complex traits include height, circadian rhythms, enzyme kinetics, and many diseases including diabetes and Parkinson's disease. One major goal of genetic research today is to better understand the molecular mechanisms through which genetic variants act to influence complex traits.

The infinitesimal model, also known as the polygenic model, is a widely used statistical model in quantitative genetics and in genome-wide association studies. Originally developed in 1918 by Ronald Fisher, it is based on the idea that variation in a quantitative trait is influenced by an infinitely large number of genes, each of which makes an infinitely small (infinitesimal) contribution to the phenotype, as well as by environmental factors. In "The Correlation between Relatives on the Supposition of Mendelian Inheritance", the original 1918 paper introducing the model, Fisher showed that if a trait is polygenic, "then the random sampling of alleles at each gene produces a continuous, normally distributed phenotype in the population". However, the model does not necessarily imply that the trait must be normally distributed, only that its genetic component will be so around the average of that of the individual's parents. The model served to reconcile Mendelian genetics with the continuous distribution of quantitative traits documented by Francis Galton.

The Omnigenic Model, first proposed by Evan A. Boyle, Yang I. Li, and Jonathan K. Pritchard, describes a hypothesis regarding the heritability of complex traits. Expanding beyond polygenes, the authors propose that all genes expressed within a cell affect the expression of a given trait. In addition, the model states that the peripheral genes, ones that do not have a direct impact on expression, explain more heritability of traits than core genes, ones that have a direct impact on expression. The process that the authors propose that facilitates this effect is called “network pleiotropy”, in which peripheral genes can affect core genes, not by having a direct effect, but rather by virtue of being mediated within the same cell.

In genetics, when multiple copies of a beneficial mutation become established and fix together it is called soft sweep. Depending on the origin of these copies, linked variants might then be retained and emerge as haplotype structures in the population. There are two major forms of soft sweeps:

References

  1. 1 2 Pritchard, Jonathan K.; Pickrell, Joseph K.; Coop, Graham (2010-02-23). "The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation". Current Biology. 20 (4): R208–215. doi:10.1016/j.cub.2009.11.055. ISSN   1879-0445. PMC   2994553 . PMID   20178769.
  2. ↑ Smith, J. M.; Haigh, J. (1974-02-01). "The hitch-hiking effect of a favourable gene". Genetical Research. 23 (1): 23–35. doi: 10.1017/S0016672300014634 . PMID   4407212.
  3. ↑ Hermisson, Joachim; Pennings, Pleuni S. (2005-04-01). "Soft sweeps: molecular population genetics of adaptation from standing genetic variation". Genetics. 169 (4): 2335–2352. doi:10.1534/genetics.104.036947. ISSN   0016-6731. PMC   1449620 . PMID   15716498.
  4. ↑ Pritchard, Jonathan K.; Di Rienzo, Anna (October 2010). "Adaptation - not by sweeps alone". Nature Reviews. Genetics. 11 (10): 665–667. doi:10.1038/nrg2880. ISSN   1471-0064. PMC   4652788 . PMID   20838407.
  5. ↑ Burke, Molly K.; Dunham, Joseph P.; Shahrestani, Parvin; Thornton, Kevin R.; Rose, Michael R.; Long, Anthony D. (2010). "Genome-wide analysis of a long-term evolution experiment with Drosophila". Nature. 467 (7315): 587–590. doi:10.1038/nature09352. PMID   20844486. S2CID   205222217.
  6. ↑ Turchin, Michael C.; Chiang, Charleston W. K.; Palmer, Cameron D.; Sankararaman, Sriram; Reich, David; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Hirschhorn, Joel N. (2012-09-01). "Evidence of widespread selection on standing variation in Europe at height-associated SNPs" (PDF). Nature Genetics. 44 (9): 1015–1019. doi:10.1038/ng.2368. ISSN   1546-1718. PMC   3480734 . PMID   22902787.
  7. ↑ Berg, Jeremy J.; Coop, Graham (2014-08-01). "A population genetic signal of polygenic adaptation". PLOS Genetics. 10 (8): e1004412. doi: 10.1371/journal.pgen.1004412 . ISSN   1553-7404. PMC   4125079 . PMID   25102153.
  8. ↑ Mathieson, Iain; Lazaridis, Iosif; Rohland, Nadin; Mallick, Swapan; Patterson, Nick; Roodenberg, Songül Alpaslan; Harney, Eadaoin; Stewardson, Kristin; Fernandes, Daniel (2015-12-24). "Genome-wide patterns of selection in 230 ancient Eurasians". Nature. 528 (7583): 499–503. doi:10.1038/nature16152. ISSN   1476-4687. PMC   4918750 . PMID   26595274.
  9. ↑ Robinson, Matthew R.; Hemani, Gibran; Medina-Gomez, Carolina; Mezzavilla, Massimo; Esko, Tonu; Shakhbazov, Konstantin; Powell, Joseph E.; Vinkhuyzen, Anna; Berndt, Sonja I. (2015-11-01). "Population genetic differentiation of height and body mass index across Europe". Nature Genetics. 47 (11): 1357–1362. doi:10.1038/ng.3401. ISSN   1546-1718. PMC   4984852 . PMID   26366552.
  10. 1 2 Field, Yair; Boyle, Evan A.; Telis, Natalie; Gao, Ziyue; Gaulton, Kyle J.; Golan, David; Yengo, Loic; Rocheleau, Ghislain; Froguel, Philippe (2016-11-11). "Detection of human adaptation during the past 2000 years". Science. 354 (6313): 760–764. doi:10.1126/science.aag0776. ISSN   1095-9203. PMC   5182071 . PMID   27738015.
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