Genetic load

Last updated

Genetic load is the difference between the fitness of an average genotype in a population and the fitness of some reference genotype, which may be either the best present in a population, or may be the theoretically optimal genotype. The average individual taken from a population with a low genetic load will generally, when grown in the same conditions, have more surviving offspring than the average individual from a population with a high genetic load. [1] [2] Genetic load can also be seen as reduced fitness at the population level compared to what the population would have if all individuals had the reference high-fitness genotype. [3] High genetic load may put a population in danger of extinction.

Contents

Fundamentals

Consider n genotypes , which have the fitnesses and frequencies , respectively. Ignoring frequency-dependent selection, the genetic load may be calculated as:

where is either some theoretical optimum, or the maximum fitness observed in the population. In calculating the genetic load, must be actually found in at least a single copy in the population, and is the average fitness calculated as the mean of all the fitnesses weighted by their corresponding frequencies:

where the genotype is and has the fitness and frequency and respectively.

One problem with calculating genetic load is that it is difficult to evaluate either the theoretically optimal genotype, or the maximally fit genotype actually present in the population. [4] This is not a problem within mathematical models of genetic load, or for empirical studies that compare the relative value of genetic load in one setting to genetic load in another.

Causes

Deleterious mutation

Deleterious mutation load is the main contributing factor to genetic load overall. [5] The Haldane-Muller theorem of mutation–selection balance says that the load depends only on the deleterious mutation rate and not on the selection coefficient. [6] Specifically, relative to an ideal genotype of fitness 1, the mean population fitness is where U is the total deleterious mutation rate summed over many independent sites. The intuition for the lack of dependence on the selection coefficient is that while a mutation with stronger effects does more harm per generation, its harm is felt for fewer generations.

A slightly deleterious mutation may not stay in mutation–selection balance but may instead become fixed by genetic drift when its selection coefficient is less than one divided by the effective population size. [7] In asexual populations, the stochastic accumulation of mutation load is called Muller's ratchet, and occurs in the absence of beneficial mutations, when after the most-fit genotype has been lost, it cannot be regained by genetic recombination. Deterministic accumulation of mutation load occurs in asexuals when the deleterious mutation rate exceeds one per replication. [8] Sexually reproducing species are expected to have lower genetic loads. [9] This is one hypothesis for the evolutionary advantage of sexual reproduction. Purging of deleterious mutations in sexual populations is facilitated by synergistic epistasis among deleterious mutations. [10]

High load can lead to a small population size, which in turn increases the accumulation of mutation load, culminating in extinction via mutational meltdown. [11] [12]

The accumulation of deleterious mutations in humans has been of concern to many geneticists, including Hermann Joseph Muller, [13] James F. Crow, [10] Alexey Kondrashov, [14] W. D. Hamilton, [15] and Michael Lynch. [16]

Beneficial mutation

In sufficiently genetically loaded populations, new beneficial mutations create fitter genotypes than those previously present in the population. When load is calculated as the difference between the fittest genotype present and the average, this creates a substitutional load. The difference between the theoretical maximum (which may not actually be present) and the average is known as the "lag load". [17] Motoo Kimura's original argument for the neutral theory of molecular evolution was that if most differences between species were adaptive, this would exceed the speed limit to adaptation set by the substitutional load. [18] However, Kimura's argument confused the lag load with the substitutional load, using the former when it is the latter that in fact sets the maximal rate of evolution by natural selection. [19]

More recent "travelling wave" models of rapid adaptation derive a term called the "lead" that is equivalent to the substitutional load, and find that it is a critical determinant of the rate of adaptive evolution. [20] [21]

Inbreeding

Inbreeding increases homozygosity. In the short run, an increase in inbreeding increases the probability with which offspring get two copies of a recessive deleterious alleles, lowering fitnesses via inbreeding depression. [22] In a species that habitually inbreeds, e.g. through self-fertilization, a proportion of recessive deleterious alleles can be purged. [23] [24]

Likewise, in a small population of humans practicing endogamy, deleterious alleles can either overwhelm the population's gene pool, causing it to become extinct, or alternately, make it fitter. [25]

Recombination/segregation

Combinations of alleles that have evolved to work well together may not work when recombined with a different suite of coevolved alleles, leading to outbreeding depression. Segregation load occurs in the presence of overdominance, i.e. when heterozygotes are more fit than either homozygote. In such a case, the heterozygous genotype gets broken down by Mendelian segregation, resulting in the production of homozygous offspring. Therefore, there is segregation load as not all individuals have the theoretical optimum genotype. Recombination load arises through unfavorable combinations across multiple loci that appear when favorable linkage disequilibria are broken down. [26] Recombination load can also arise by combining deleterious alleles subject to synergistic epistasis, i.e. whose damage in combination is greater than that predicted from considering them in isolation. [27]

Migration

Migration load is hypothesized to occur when maladapted non-native organisms enter a new environment. [28]

On one hand, beneficial genes from migrants can increase the fitness of local populations. [29] On the other hand, migration may reduce the fitness of local populations by introducing maladptive alleles. This is hypothesized to occur when the migration rate is "much greater" than the selection coefficient. [29]

Migration load may occur by reducing the fitness of local organisms, or through natural selection imposed on the newcomers, such as by being eliminated by local predators. [30] [31] Most studies have only found evidence for this theory in the form of selection against immigrant populations, however, one study found evidence for increased mutational burden in recipient populations, as well. [32]

Related Research Articles

<span class="mw-page-title-main">Inbreeding</span> Reproduction by closely related organisms

Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and other consequences that may arise from expression of deleterious recessive traits resulting from incestuous sexual relationships and consanguinity. Animals avoid inbreeding only rarely.

Small populations can behave differently from larger populations. They are often the result of population bottlenecks from larger populations, leading to loss of heterozygosity and reduced genetic diversity and loss or fixation of alleles and shifts in allele frequencies. A small population is then more susceptible to demographic and genetic stochastic events, which can impact the long-term survival of the population. Therefore, small populations are often considered at risk of endangerment or extinction, and are often of conservation concern.

<span class="mw-page-title-main">Neutral theory of molecular evolution</span> Theory of evolution by changes at the molecular level

The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species are due to random genetic drift of mutant alleles that are selectively neutral. The theory applies only for evolution at the molecular level, and is compatible with phenotypic evolution being shaped by natural selection as postulated by Charles Darwin.

Fitness is a quantitative representation of individual reproductive success. It is also equal to the average contribution to the gene pool of the next generation, made by the same individuals of the specified genotype or phenotype. Fitness can be defined either with respect to a genotype or to a phenotype in a given environment or time. The fitness of a genotype is manifested through its phenotype, which is also affected by the developmental environment. The fitness of a given phenotype can also be different in different selective environments.

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.

Allele frequency, or gene frequency, is the relative frequency of an allele at a particular locus in a population, expressed as a fraction or percentage. Specifically, it is the fraction of all chromosomes in the population that carry that allele over the total population or sample size. Microevolution is the change in allele frequencies that occurs over time within a population.

<span class="mw-page-title-main">Genetic diversity</span> Total number of genetic characteristics in a species

Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is distinguished from genetic variability, which describes the tendency of genetic characteristics to vary.

Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate adaptive genetic diversity, and thereby evolve through natural selection.

In population genetics and population ecology, population size is a countable quantity representing the number of individual organisms in a population. Population size is directly associated with amount of genetic drift, and is the underlying cause of effects like population bottlenecks and the founder effect. Genetic drift is the major source of decrease of genetic diversity within populations which drives fixation and can potentially lead to speciation events.

<span class="mw-page-title-main">Conservation genetics</span> Interdisciplinary study of extinction avoidance

Conservation genetics is an interdisciplinary subfield of population genetics that aims to understand the dynamics of genes in a population for the purpose of natural resource management, conservation of genetic diversity, and the prevention of species extinction. Scientists involved in conservation genetics come from a variety of fields including population genetics, research in natural resource management, molecular ecology, molecular biology, evolutionary biology, and systematics. The genetic diversity within species is one of the three fundamental components of biodiversity, so it is an important consideration in the wider field of conservation biology.

Mutation–selection balance is an equilibrium in the number of deleterious alleles in a population that occurs when the rate at which deleterious alleles are created by mutation equals the rate at which deleterious alleles are eliminated by selection. The majority of genetic mutations are neutral or deleterious; beneficial mutations are relatively rare. The resulting influx of deleterious mutations into a population over time is counteracted by negative selection, which acts to purge deleterious mutations. Setting aside other factors, the equilibrium number of deleterious alleles is then determined by a balance between the deleterious mutation rate and the rate at which selection purges those mutations.

Inbreeding depression is the reduced biological fitness that has the potential to result from inbreeding. The loss of genetic diversity that is seen due to inbreeding, results from small population size. Biological fitness refers to an organism's ability to survive and perpetuate its genetic material. Inbreeding depression is often the result of a population bottleneck. In general, the higher the genetic variation or gene pool within a breeding population, the less likely it is to suffer from inbreeding depression, though inbreeding and outbreeding depression can simultaneously occur.

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.

In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilising selection through the purging of deleterious genetic polymorphisms that arise through random mutations.

In population genetics, fixation is the change in a gene pool from a situation where there exists at least two variants of a particular gene (allele) in a given population to a situation where only one of the alleles remains. That is, the allele becomes fixed. In the absence of mutation or heterozygote advantage, any allele must eventually either be lost completely from the population, or fixed, i.e. permanently established at 100% frequency in the population. Whether a gene will ultimately be lost or fixed is dependent on selection coefficients and chance fluctuations in allelic proportions. Fixation can refer to a gene in general or particular nucleotide position in the DNA chain (locus).

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.

Genetic purging is the increased pressure of natural selection against deleterious alleles prompted by inbreeding.

<span class="mw-page-title-main">Epistasis</span> Dependence of a gene mutations phenotype on mutations in other genes

Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is dependent on the genetic background in which it appears. Epistatic mutations therefore have different effects on their own than when they occur together. Originally, the term epistasis specifically meant that the effect of a gene variant is masked by that of different gene.

Evolutionary rescue is a process by which a population—that would have gone extinct in the absence of evolution—persists due to natural selection acting on heritable variation. Coined by Gomulkiewicz & Holt in 1995, evolutionary rescue was described as a continuously changing environment predicted to appear as a stable lag of the mean trait value behind a moving environmental optimum, where the rate of evolution and change in the environment are equal. Evolutionary rescue is often confused with two other commonplace forms of rescue: genetic rescue and demographic rescue-in nature due to overlapping similarities. Figure 1 highlights the different pathways that result in their respective rescue.

Bias in the introduction of variation is a theory in the domain of evolutionary biology that asserts biases in the introduction of heritable variation are reflected in the outcome of evolution. It is relevant to topics in molecular evolution, evo-devo, and self-organization. In the context of this theory, "introduction" ("origination") is a technical term for events that shift an allele frequency upward from zero. Formal models demonstrate that when an evolutionary process depends on introduction events, mutational and developmental biases in the generation of variation may influence the course of evolution by a first come, first served effect, so that evolution reflects the arrival of the likelier, not just the survival of the fitter. Whereas mutational explanations for evolutionary patterns are typically assumed to imply or require neutral evolution, the theory of arrival biases distinctively predicts the possibility of mutation-biased adaptation. Direct evidence for the theory comes from laboratory studies showing that adaptive changes are systematically enriched for mutationally likely types of changes. Retrospective analyses of natural cases of adaptation also provide support for the theory. This theory is notable as an example of contemporary structuralist thinking, contrasting with a classical functionalist view in which the course of evolution is determined by natural selection.

References

  1. ↑ Whitlock, Michael C.; Bourguet, Denis (2000). "Factors affecting the genetic load in Drosophila: synergistic epistasis and correlations among fitness components" (PDF). Evolution. 54 (5): 1654–1660. doi:10.1554/0014-3820(2000)054[1654:FATGLI]2.0.CO;2. PMID   11108592. S2CID   44511613.
  2. ↑ Crist, Kathryn Carvey; Farrar, Donald R. (1983). "Genetic load and long-distance dispersal in Asplenium platyneuron". Canadian Journal of Botany. 61 (6): 1809–1814. doi:10.1139/b83-190.
  3. ↑ JF Crow (1958). "Some possibilities for measuring selection intensities in man". Human Biology. 30 (1): 1–13. PMID   13513111.
  4. ↑ Agrawal, Aneil F.; Whitlock, Michael C. (2012). "Mutation load: the fitness of individuals in populations where deleterious alleles are abundant". Annual Review of Ecology, Evolution, and Systematics. 43 (1): 115–135. doi:10.1146/annurev-ecolsys-110411-160257.
  5. ↑ Klekowski, EdwardJ. (1988). "Genetic load and its causes in long-lived plants". Trees. 2 (4): 195–203. doi:10.1007/BF00202374. S2CID   24058154.
  6. ↑ Bürger, Reinhard (1998). "Mathematical properties of mutation-selection models". Genetica. 102/103: 279–298. doi:10.1023/a:1017043111100. S2CID   22885529.
  7. ↑ Lande, Russell (October 1994). "Risk of Population Extinction from Fixation of New Deleterious Mutations". Evolution. 48 (5): 1460–1469. doi:10.2307/2410240. JSTOR   2410240. PMID   28568413.
  8. ↑ Kondrashov, A. S. (1988). "Deleterious mutations and the evolution of sexual reproduction". Nature . 336 (6198): 435–440. Bibcode:1988Natur.336..435K. doi:10.1038/336435a0. PMID   3057385. S2CID   4233528.
  9. ↑ Marriage, Tara N. (2009). Mutation, asexual reproduction and genetic load: A study in three parts (Ph.D. thesis). University of Kansas.
  10. 1 2 Crow, James F. (5 August 1997). "The high spontaneous mutation rate: Is it a health risk?". Proceedings of the National Academy of Sciences. 94 (16): 8380–8386. Bibcode:1997PNAS...94.8380C. doi: 10.1073/pnas.94.16.8380 . ISSN   0027-8424. PMC   33757 . PMID   9237985.
  11. ↑ Lynch, Michael; Conery, John; Burger, Reinhard (December 1995). "Mutational Meltdowns in Sexual Populations". Evolution. 49 (6): 1067–1080. doi:10.2307/2410432. JSTOR   2410432. PMID   28568521.
  12. ↑ Lynch, Michael; Conery, John; Burger, Reinhard (1 January 1995). "Mutation Accumulation and the Extinction of Small Populations". The American Naturalist. 146 (4): 489–518. doi:10.1086/285812. JSTOR   2462976. S2CID   14762497.
  13. ↑ Muller, H. J. (1 June 1950). "Our load of mutations". American Journal of Human Genetics. 2 (2): 111–176. ISSN   0002-9297. PMC   1716299 . PMID   14771033.
  14. ↑ Kondrashov, Alexey S. (21 August 1995). "Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over?". Journal of Theoretical Biology. 175 (4): 583–594. Bibcode:1995JThBi.175..583K. doi: 10.1006/jtbi.1995.0167 . PMID   7475094.
  15. ↑ Hamilton, W.D. Narrow Roads of Gene Land vol. 2: Evolution of Sex. pp. 449–463.
  16. ↑ Lynch, M. (7 March 2016). "Mutation and Human Exceptionalism: Our Future Genetic Load". Genetics. 202 (3): 869–875. doi:10.1534/genetics.115.180471. PMC   4788123 . PMID   26953265.
  17. ↑ Smith, J. Maynard (1 January 1976). "What Determines the Rate of Evolution?". The American Naturalist. 110 (973): 331–338. doi:10.1086/283071. JSTOR   2459757. S2CID   85575105.
  18. ↑ Kimura, Motoo (1968). "Evolutionary rate at the molecular level" (PDF). Nature. 217 (5129): 624–626. Bibcode:1968Natur.217..624K. doi:10.1038/217624a0. PMID   5637732. S2CID   4161261.
  19. ↑ Ewens, Warren J. (2003). Mathematical population genetics (2nd ed.). New York: Springer. p.  78. ISBN   978-0387201917.
  20. ↑ Desai, M. M.; Fisher, D. S. (4 May 2007). "Beneficial Mutation Selection Balance and the Effect of Linkage on Positive Selection". Genetics. 176 (3): 1759–1798. doi:10.1534/genetics.106.067678. PMC   1931526 . PMID   17483432.
  21. ↑ Bertram, J; Gomez, K; Masel, J (February 2017). "Predicting patterns of long-term adaptation and extinction with population genetics". Evolution. 71 (2): 204–214. arXiv: 1605.08717 . doi:10.1111/evo.13116. PMID   27868195. S2CID   4705439.
  22. ↑ Saccheri, I. J.; Lloyd, H. D.; Helyar, S. J.; Brakefield, P. M. (2005). "Inbreeding uncovers fundamental differences in the genetic load affecting male and female fertility in a butterfly". Proceedings of the Royal Society B: Biological Sciences. 272 (1558): 39–46. doi:10.1098/rspb.2004.2903. PMC   1634945 . PMID   15875568.
  23. ↑ Byers, D. L.; Waller, D. M. (1999). "Do plant populations purge their genetic load? Effects of population size and mating history on inbreeding depression". Annual Review of Ecology and Systematics. 30 (1): 479–513. doi:10.1146/annurev.ecolsys.30.1.479.
  24. ↑ Barrett, S. C. H.; Charlesworth, D. (1991). "Effects of a change in the level of inbreeding on the genetic load". Nature. 352 (6335): 522–524. Bibcode:1991Natur.352..522B. doi:10.1038/352522a0. PMID   1865906. S2CID   4240051.
  25. ↑ Pala, M.; Zappala, Z.; Marongiu, M. (2017). "Population and individual-specific regulatory variation in Sardinia". Nature Genetics. 49 (5): 700–707. doi:10.1038/ng.3840. PMC   5411016 . PMID   28394350. S2CID   4240051.
  26. ↑ Haag, C. R.; Roze, D. (2007). "Genetic load in sexual and asexual diploids: segregation, dominance and genetic drift". Genetics. 176 (3): 1663–1678. doi:10.1534/genetics.107.073080. PMC   1931546 . PMID   17483409.
  27. ↑ King, J. (1966). "The gene interaction component of the genetic load". Genetics. 53 (3): 403–413. doi:10.1093/genetics/53.3.403. PMC   1211027 . PMID   5919323.
  28. ↑ Bolnick, Daniel I. (2007). "Natural selection in populations subject to a migration load". Evolution. 61 (9): 2229–2243. doi:10.1111/j.1558-5646.2007.00179.x. PMID   17767592. S2CID   25685919.
  29. 1 2 Hu, Xin-Sheng; Li, Bailian (2003). "On migration load of seeds and pollen grains in a local population". Heredity. 90 (2): 162–168. doi: 10.1038/sj.hdy.6800212 . PMID   12634823. "Gene flow can homogenize the genetic divergence among populations. On the one hand, effects of genetic drift in small local populations can be effectively reduced when the average number of migrants is greater than one (Wright, 1969), beneficial immigrant genes can shift local populations to a higher fitness peak (Barton and Whitlock, 1997). On the other hand, gene flow between populations adapted to different environments can cause maladaptation in a recipient population, resulting in migration load, a reduction in population fitness. If the migration rate is much greater than the selection coefficient, migrant alleles can even swamp out locally adaptive alleles (Wright, 1969)."
  30. ↑ Bolnick 2007 : "A second consequence of migration–selection balance is known as “migration load” (Garcia-Ramos and Kirkpatrick 1997). This is the loss in mean fitness of a population that results from immigration of locally maladapted alleles. Migration load is analogous to the “mutation load” that arises when mutation inputs new alleles that, on average, are expected to be less fit than existing alleles. Although both migration and mutation have the potential to import locally beneficial novel alleles that promote adaptation (Kawecki 2000), immigrants from other environments may frequently carry alleles that are less fit in the local habitat. Consequently, in addition to constraining divergence among populations, migration displaces recipient populations from their local adaptive peaks. For Mendelian traits, this entails a reduction in the frequency of locally favored alleles that otherwise would be at or near fixation, whereas quantitative traits may be displaced from the mean value favored by selection."
  31. ↑ Bolnick 2007 :"Given this life history, the homogenizing effects of migration are expected to be most obvious early in a generation, after which natural selection by visual predators presumably eliminates many immigrants."
  32. ↑ Bolnick 2007 : To date, support for migration load has generally been confined to studies of individual populations, in which selection operates against immigrants (King 1992; Sandoval 1994a; Hendry et al. 2002; Moore and Hendry 2005).
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.