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. 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. 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. 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 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