Genetic load

In population genetics, genetic load or genetic burden is a measure of the cost of lost alleles due to selection (selectional load) or mutation (mutational load). It is a value in the range 0 < L < 1, where 0 represents no load. The concept was first formulated in 1937 by JBS Haldane, independently formulated, named and applied to humans in 1950 by H. J. Muller,^[1] and elaborated further by Haldane in 1957.^[2]

Definition

Genetic load is the reduction in selective value for a population compared to what the population would have if all individuals had the most favored genotype.^[3] It is normally stated in terms of fitness as the reduction in the mean fitness for a population compared to the maximum fitness.

Mathematics

Consider a single gene locus with the alleles $\mathbf{A} _1 \dots \mathbf{A} _n$, which have the fitnesses $w_1 \dots w_n$ and the allele frequencies $p_1 \dots p_n$ respectively. Ignoring frequency-dependent selection, then genetic load (L) may be calculated as:

$L = {{w_\max - \bar w}\over w_\max}~~~~~~~~~~(1)$

where w_max  is the maximum value of the fitnesses $w_1 \dots w_n$ and $\bar w$ is mean fitness which is calculated as the mean of all the fitnesses weighted by their corresponding allele frequency:

$\bar w = {\sum_{i=1}^n {p_i w_i}} ~~~~~~~~~~(2)$

where the i^th allele is $\mathbf{A}_i$ and has the fitness and frequency w_i and p_i respectively.

When the w_max  = 1, then (1) simplifies to

$L = 1 - \bar w. ~~~~~~~~~~(3)$

Causes of genetic load

Load may be caused by selection and mutation.

Mutational load

Mutational load is caused when a mutation at a locus produces a new allele of either lesser or greater fitness than the mean fitness of the population. This lowers the average fitness of the population; a deleterious mutation has a lower relative fitness, lowering average load, while an advantageous mutation effectively decreases the relative fitness of the existing alleles, and thus also decreases the mean fitness.

Selectional load

Selection occurs when the fitnesses of particular alleles are inequal, hence selection always exerts a load. This occurs due to natural selection in cases were a particular combination of alleles is favoured on another. In some cases like for example in the case of sickle cell anaemia, heterozygous for this trait or carriers are favoured in cases of malaria and other cases, that is, homozygous normal and sickle cell anaemia are not favoured and die off.

With directional selection, the allele frequencies will tend towards an equilibrium position with the fittest allele reaching a frequency in mutation-selection balance. As mutations are rare, this is effectively fixation. Consider two alleles $\mathbf{A}_1$ and $\mathbf{A}_2$. If w₁ > w₂, then at equilibrium, $p_1 \approx 1$ and $p_2 \approx 0$, hence $\bar{w} \approx w_\max$, and $L \approx 0$.

If the mean fitness is 0, the load is equal to 1, but the population goes extinct.

See also

• Haldane's dilemma

Segregational load

In contrast to directional selection, in which one heterozygote has a higher fitness than other homozygote, heterozygote advantage (also called overdominance) always exerts a load against the less fit homozygotes at equilibrium.

References

1. ^ Muller, H. J. (1950). "Our load of mutations". Am J Hum Genet 2 (2): 111–76. PMC 1716299. PMID 14771033. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1716299. 
2. ^ JBS Haldane (1957). "The cost of natural selection". Journal of Genetics 55 (3): 511–524. doi:10.1007/BF02984069. http://www.blackwellpublishing.com/ridley/classictexts/haldane2.pdf. 
3. ^ JF Crow (1958). "Some possibilities for measuring selection intensities in man". Hum. Biol 30 (1): 1–13. PMID 13513111. 

External links

• The Cost of Natural Selection Revisited, Leonard Nunney, Ann. Zool. Fennici 40:185-194 (pdf file)
• Genetic load, from Evolution A-Z by Mark Ridley
• Creationist Claim CB120: Genetic load from An Index to Creationist Claims by Mark Isaak