Genetic load

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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 the result of nonnative organisms that aren't adapted to a particular environment coming into that environment. If they breed with individuals who are adapted to that environment, their offspring will not be as fit as they would have been if both of their parents had been adapted to that particular environment. [28] [29] [30] Migration load can also occur in asexually reproducing species, but in this case, purging of low fitness genotypes is more straightforward.

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 incest only rarely.

Genetic drift, also known as random genetic drift, allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.

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>

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 the 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.

<span class="mw-page-title-main">Muller's ratchet</span> Accumulation of harmful mutations

In evolutionary genetics, Muller's ratchet is a process which, in the absence of recombination, results in an accumulation of irreversible deleterious mutations. This happens because in the absence of recombination, and assuming reverse mutations are rare, offspring bear at least as much mutational load as their parents. Muller proposed this mechanism as one reason why sexual reproduction may be favored over asexual reproduction, as sexual organisms benefit from recombination and consequent elimination of deleterious mutations. The negative effect of accumulating irreversible deleterious mutations may not be prevalent in organisms which, while they reproduce asexually, also undergo other forms of recombination. This effect has also been observed in those regions of the genomes of sexual organisms that do not undergo recombination.

In evolutionary genetics, mutational meltdown is a sub class of extinction vortex in which the environment and genetic predisposition mutually reinforce each other. Mutational meltdown is the accumulation of harmful mutations in a small population, which leads to loss of fitness and decline of the population size, which may lead to further accumulation of deleterious mutations due to fixation by genetic drift.

<span class="mw-page-title-main">Evolution of sexual reproduction</span> How sexually reproducing multicellular organisms could have evolved from a common ancestor species

Sexual reproduction is an adaptive feature which is common to almost all multicellular organisms and various unicellular organisms. Currently, the adaptive advantage of sexual reproduction is widely regarded as a major unsolved problem in biology. As discussed below, one prominent theory is that sex evolved as an efficient mechanism for producing variation, and this had the advantage of enabling organisms to adapt to changing environments. Another prominent theory, also discussed below, is that a primary advantage of outcrossing sex is the masking of the expression of deleterious mutations. Additional theories concerning the adaptive advantage of sex are also discussed below. Sex does, however, come with a cost. In reproducing asexually, no time nor energy needs to be expended in choosing a mate and, if the environment has not changed, then there may be little reason for variation, as the organism may already be well-adapted. However, very few environments have not changed over the millions of years that reproduction has existed. Hence it is easy to imagine that being able to adapt to changing environment imparts a benefit. Sex also halves the amount of offspring a given population is able to produce. Sex, however, has evolved as the most prolific means of species branching into the tree of life. Diversification into the phylogenetic tree happens much more rapidly via sexual reproduction than it does by way of asexual reproduction.

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 and extinction prevention. Researchers involved in conservation genetics come from a variety of fields including population genetics, natural resources, molecular ecology, biology, evolutionary biology, and systematics. Genetic diversity is one of the three fundamental measures 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 which has the potential to result from inbreeding. 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.

The infinite alleles model is a mathematical model for calculating genetic mutations. The Japanese geneticist Motoo Kimura and American geneticist James F. Crow (1964) introduced the infinite alleles model, an attempt to determine for a finite diploid population what proportion of loci would be homozygous. This was, in part, motivated by assertions by other geneticists that more than 50 percent of Drosophila loci were heterozygous, a claim they initially doubted. In order to answer this question they assumed first, that there were a large enough number of alleles so that any mutation would lead to a different allele ; and second, that the mutations would result in a number of different outcomes from neutral to deleterious.

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 reduction of the frequency of a deleterious allele, caused by an increased efficiency of natural selection 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.

References

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  28. ↑ Bolnick, Daniel I.; Nosil, Patrik (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. ↑ 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.
  30. ↑ Ilkka Hanski; Oscar E. Gaggiotti, eds. (2004). Ecology, Genetics, and Evolution of Metapopulations. Academic Press. ISBN   978-0-12-323448-3.
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