Genetic load
Genetic load is a concept that quantifies the presence of deleterious alleles—genes that can cause harmful effects—within a population. These alleles can be recessive, meaning they are often masked by normal counterparts, and their persistence in a gene pool is primarily maintained through the processes of mutation and natural selection. Genetic load plays a significant role in inbreeding depression, which refers to the reduced fitness of offspring resulting from the mating of closely related individuals. This is particularly relevant in fields like agriculture, animal husbandry, conservation biology, and human health.
The genetic load is comprised of two main components: lethal alleles, which can lead directly to death, and nonlethal alleles, which may still negatively impact an organism's fitness. The presence of these alleles is influenced by factors such as population size, mating systems, and mutation rates. Smaller populations or those that experience partial inbreeding are more susceptible to accumulating genetic load, potentially leading to a higher risk of extinction. Additionally, external factors like environmental toxins or radiation can increase mutation rates, further contributing to genetic load. Understanding genetic load is crucial for managing biodiversity and the health of various species.
Genetic load
SIGNIFICANCE: Genetic load is a measure of the number of recessive deleterious (lethal or sublethal) alleles in a population. These alleles are maintained in populations at equilibrium frequencies by mutation (which introduces new alleles into the gene pool) and selection (which eliminates unfavorable alleles from the gene pool). Genetic load is one of the causes of inbreeding depression, the reduced viability of offspring from closely related individuals. For this reason, genetic load is a primary concern in the fields of agriculture, animal husbandry, conservation biology, and human health.
Genetic Load in Diploid Populations
Genetic diversity is a measure of the total number of alleles within a population, and it is mutation, the ultimate source of all genetic variation, that gives rise to new alleles. Favorable mutations are rare and are greatly outnumbered by mutations that are selectively neutral or deleterious (that is, lethal or sublethal). In organisms, most deleterious mutant alleles are hidden from view because they are typically (but not always) recessive and are masked by a second, normal or wild-type allele. On the other hand, in organisms, lethal and deleterious genes are immediately exposed to differential selection.
Genetic load is defined as an estimate of the number of deleterious alleles in a population. Total is therefore the sum of two major components, the lethal load (L) and the detrimental but nonlethal load (D). Empirical and theoretical studies suggest that detrimental rather than lethal alleles constitute the majority of the genetic load in natural populations. When expressed in the condition, the primary effect of deleterious alleles within the on individuals is straightforward: death or disability accompanied by lower fitness. However, the impact of lethal and sublethal alleles on the mean fitness of populations, as opposed to individuals, is dependent on many factors, such as their frequency within the gene pool, the number of individuals in the population, and whether or not those individuals are randomly mating.
How and why are recessive alleles maintained within a population at all? Why are they not eliminated by natural selection? First, recessive deleterious alleles must obtain a sufficient frequency before homozygous individuals occur in a sufficient number to be detected. Second, in some situations recessive alleles that are deleterious or lethal in the homozygous state are advantageous in heterozygotes. Third, new deleterious alleles are constantly introduced into the population by mutation or are reintroduced by back mutation. Finally, the rate at which deleterious genes are purged from the population critically depends on the “cost of selection” against them, and selection coefficients may vary considerably depending on the allele and the intra- or extracellular environments. In large randomly mating diploid populations, genetic load theoretically reaches an “equilibrium value” maintained by a balance between the mutation rate and the strength of selection. Finally, it should be borne in mind that nonlethal alleles that are not advantageous under present circumstances nevertheless constitute a pool of alleles that may be advantageous in a different (or changing) environment or a different genetic background. In other words, some neutral and nonlethal mutations may have unpredictable “remote consequences.”
Population Size, Inbreeding, and Genetic Load
As it is used among population geneticists, genetic load is most appropriately defined as the proportionate decrease in the average fitness of a population relative to that of the optimal genotype. The “proportionate decrease in the average fitness” is, of course, due to the presence of lethal and deleterious nonlethal alleles that are maintained in equilibrium by mutation and selection. Genetic load within populations may be substantially increased under certain circumstances. Small populations, species whose mating system involves complete or partial inbreeding, and populations with increased mutation rates all are expected to accumulate load at values exceeding that of large outbreeding populations. Small populations face multiple genetic hazards, including inbreeding depression.
Inbreeding decreases heterozygosity across loci, and the fitness of inbred individuals is typically depressed relative to randomly mating populations. Inbreeding causes rare recessive alleles to occur more frequently in the homozygous condition, increasing the frequency of aberrant phenotypes that are observed. Complete or partial inbreeding (or, in plants, self-fertilization) leads to the accumulation of deleterious mutations that increase genetic load. Paradoxically, continued inbreeding results in lower equilibrium frequencies of deleterious alleles because they are expressed with greater frequency in the homozygous state. Thus, inbreeding populations may eliminate, or “purge,” some proportion of their genetic load via selection against deleterious recessive alleles. Nevertheless, it is true that compared to large, genetically diverse populations, small, inbred populations with reduced genetic diversity are more likely to go extinct. For these reasons, population sizes, inbreeding, and genetic load are among the primary concerns of conservation biologists working to ensure the survival of rare or endangered species.
As previously mentioned, increased mutation rates may also increase genetic load. For example, the rate of nucleotide substitution in mammalian mitochondrial DNA (mtDNA) is nearly ten times that of nuclear DNA. The tenfold difference in mutation rate is postulated to be due to highly toxic, mutagenic reactive oxygen species produced by the mitochondrial and/or relatively inefficient DNA repair mechanisms. Thus, mitochondrial genomes accumulate fixed nucleotide changes rapidly via “Müller’s ratchet.” Mutation rates and genetic load may also be increased by exposure to harmful environments. For example, an accident on April 25, 1986, at the Chernobyl nuclear power plant in Ukraine released 5 percent of the radioactive reactor core into the atmosphere, contaminating large areas of Belarus, Ukraine, and Russia. Radiation exposure of this kind and toxic chemicals (such as heavy metals) in watersheds pose significant human health risks that, over time, may be associated with increased genetic loads in affected populations.
Key Terms
- deleterious allelesalternative forms of a gene that, when expressed in the homozygous condition in diploid organisms, may be lethal or sublethal, in the latter case typically resulting in an aberrant phenotype with low fitness
- inbreeding depressionreduced fitness of an individual or population arising as the result of decreased heterozygosity across loci
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