Genetic load

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. 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. High genetic load may put a population in danger of extinction. 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. 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. High genetic load may put a population in danger of extinction. Consider n genotypes A 1 , … , A n {displaystyle mathbf {A} _{1},dots ,mathbf {A} _{n}} , which have the fitnesses w 1 , … , w n {displaystyle w_{1},dots ,w_{n}} and frequencies p 1 , … , p n {displaystyle p_{1},dots ,p_{n}} , respectively. Ignoring frequency-dependent selection, the genetic load L {displaystyle L} may be calculated as: where w max {displaystyle w_{max }} is either some theoretical optimum, or the maximum fitness observed in the population. In calculating the genetic load, w 1 … w n {displaystyle w_{1}dots w_{n}} must be actually found in at least a single copy in the population, and w ¯ {displaystyle {ar {w}}} is the average fitness calculated as the mean of all the fitnesses weighted by their corresponding frequencies: where the i t h {displaystyle i^{mathrm {th} }} genotype is A i {displaystyle mathbf {A} _{i}} and has the fitness and frequency w i {displaystyle w_{i}} and p i {displaystyle p_{i}} 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. 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. Deleterious mutation load is the main contributing factor to genetic load overall. Most mutations are deleterious, and occur at a high rate. 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. Specifically, relative to an ideal genotype of fitness 1, the mean population fitness is exp ⁡ ( − U ) {displaystyle exp(-U)} 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. 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. Sexually reproducing species are expected to have lower genetic loads. 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. High load can lead to a small population size, which in turn increases the accumulation of mutation load, culminating in extinction via mutational meltdown. The accumulation of deleterious mutations in humans has been of concern to many geneticists, including Hermann Joseph Muller, James F. Crow, Alexey Kondrashov, W. D. Hamilton, and Michael Lynch.