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.
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
averagefitness 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]
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.
^Crist, Kathryn Carvey; Farrar, Donald R. (1983). "Genetic load and long-distance dispersal in Asplenium platyneuron". Canadian Journal of Botany. 61 (6): 1809–1814.
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^JF Crow (1958). "Some possibilities for measuring selection intensities in man". Human Biology. 30 (1): 1–13.
PMID13513111.
^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.
^Klekowski, EdwardJ. (1988). "Genetic load and its causes in long-lived plants". Trees. 2 (4): 195–203.
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10.1007/BF00202374.
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^Lande, Russell (October 1994). "Risk of Population Extinction from Fixation of New Deleterious Mutations". Evolution. 48 (5): 1460–1469.
doi:
10.2307/2410240.
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PMID28568413.
^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.
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S2CID14762497.
^Smith, J. Maynard (1 January 1976). "What Determines the Rate of Evolution?". The American Naturalist. 110 (973): 331–338.
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10.1086/283071.
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S2CID85575105.
^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.