What is Balancing Selection in Biology?

What is Balancing Selection in Biology?

Natural selection is a key mechanism of evolution, and a primary explanation for adaptive evolution. It can be classified into various types depending on the differentiating factor. When it is classified on the basis of the effect on genetic diversity, the concept of balancing selection is put forth. This article attempts to explain this concept with the help of examples.
Theodosius Dobzhansky was a Russian geneticist and evolutionary biologist whose work was instrumental in propagating the concept that natural selection occurred via mutations in genes.

Selection, if classified according to its effect on genetic diversity, can be categorized as purifying selection and balancing selection. Purifying selection or negative selection brings about a stabilization in an organism's genome, by conducting a deletion or removal of all genetic alleles that may prove harmful or deleterious towards the organism. In such a selection, due to the presence of the deleterious allele, the virility and fecundity of the organism is compromised. This leads to the carriers of the allele to produce fewer and fewer offspring in each consecutive generation, till it ultimately becomes incapable of reproduction and the allele is lost.

This gradual reduction in the number of progeny results in the considerable dilution of the allelic frequency in the population, thereby achieving a reduction in genetic diversity. Another reason why the organism eventually perishes in such a case is the fact that non-deleterious alleles that are in the proximity of this allele are also sometimes victims of incidental purging, hence there is considerable genetic loss at each generation.

In contrast, balancing selection is a process in which genetic diversity is not only maintained but is also increased in any given population. It involves a number of selective processes that result in the active retention of multiple alleles of various genes in the gene pool of the organism. The frequencies of these alleles are more than those of genetic mutations, hence the DNA repair system does not misinterpret them as mutations and therefore does not attempt to correct them.

The difference between two alleles could range from a SNP (single nucleotide polymorphism) to changes in entire stretches of DNA sequence. The various forms of alleles are maintained by balancing selection in a dynamic balance between the advantageous and disadvantageous alleles. This helps maintain genotypic as well as phenoytypic diversity in the population, and also allows that population to be highly adaptable to their surroundings, as they already possess alleles that may prove beneficial. Also, this process is quicker than waiting for the evolution and development of a suitable genetic allele. This type of selection occurs via two mechanisms - heterozygote advantage and frequency-dependent selection.

Mechanisms of Balancing Selection

Heterozygote Advantage Selection

It is also called heterotic balancing selection, and it favors the proliferation of individuals who are heterozygous for a particular gene. Both homozygous forms - dominant and recessive - are not given preference. Also, the relative fitness of the heterozygote is significantly higher than that of the homozygotes. Such an advantage conferred by the state of heterozygosity is called overdominance. It is a genetic concept where the phenotype exhibited by the heterozygote is not only distinctly dissimilar but also lies well outside the range of the phenotype displayed by either homozygote.

From a theoretical viewpoint, this can be explained by considering two populations of the same sexual organisms. If both are maintained in isolation from each other for a certain period of time, it follows logically that genetic drift will occur, causing a change in the genetic diversity. Any positive changes are an added advantage, but in the event of any negative changes, it is extremely unlikely that both these populations would develop exactly the same deleterious alleles/mutations. Any loss of function mutations that may occur will also not be much of a threat since they are usually recessive in nature. Now, if individuals from both these populations are bred with each other, it will inherit the positive qualities from each parent. Any negative quality inherited will have no effect as it would be recessive and hence would not be expressed in the heterozygote. Therefore the hybrid offspring will have advantages of both parents yet not as many disadvantages as either of the two parents, i.e. it will be fitter than both its parents. This is also the major underlying principle for heterosis or "hybrid vigor".

A well documented case that exhibits this mechanism is found in the gene responsible for the development of sickle cell anemia (SCA). SCA or drepanocytosis, is a hereditary genetic blood disorder, that is recessive in nature. The SCA gene possesses a mutation in the hemoglobin gene which leads to abnormal folding of the molecule itself, this in turn hampers it to form a globular structure, leading to a RBC (red blood cell) having an elongated structure (sickle-shaped). Also, due to this, oxygen does not bind properly to the molecule, leading to insufficient supply of oxygen to the body. This causes the affected individual, who is homozygotic for this gene, to suffer from anemia, damage to internal organs, frailty, and susceptibility to diseases. However for individuals who are heterozygous, one normal allele and one mutated allele, the condition does not manifest (as it is recessive), and these individuals are known as carriers.

The unique feature of possessing this allele is that it renders the individual resistant to malaria infection by the Plasmodium parasite. This parasite, during the course of infection, spends a part of its life cycle in red blood cells where it matures. In individuals with normal RBC's, the malarial parasite infects these cells, brings about a rapid decrease in the oxygen levels of the cell, recruits and rearranges the actin cytoskeleton of the cell, causing it to form a cleft shape that stick to the walls of the blood vessels. Due to this sticking, the cells are not transported to the liver, and hence are not destroyed, giving rise to a full-blown case of malaria. In case of people with homozygous and heterozygous sickle cell conditions, the parasite is unable to carry out the reorganization of actin molecules, hence the cell does not stick to the vessel walls, and travels to the liver, where it is promptly recognized by the immune system and destroyed, hence averting a malarial infection. Even though the homozygotes survive, the SCA condition itself proves fatal to them eventually, therefore the heterozygote proves to be fitter in comparison, as not only does it not have the SCA disorder but it also possesses resistance to malaria. Other examples include:
  • HLA-DRB1 heterozygosity imparting resistance to hepatitis C
  • MHC heterozygosity leads to possession of a wider range for immune response.
  • CFTR (cystic fibrosis) heterozygosity increases survival chances in case of cholera, tuberculosis, and diarrhea.

Frequency-dependent Selection

It is a type of selection that involves a change in the fitness of a phenotype expressed by an organism depending on the frequency of that particular phenotype in the population, with respect to other phenotypes. It is the result of interactions between prey-predator species, or between genotypes of competitive organisms. They evolve over the course of time to show anti-predator functions. There are two type of diverse types that are as follows.

Negative Frequency-dependent Selection

It exhibits a decrease in the fitness if the phenotype is more common, and an increase if the phenotype is rare. It was first described by Edward Bagnall Poulton in 1884 with respect to the maintenance of color polymorphisms in the prey by the predator organisms. Theoretically, if one were to explain this concept, consider a species of snails that are preyed upon by a species of birds. The snails exhibit two different phenotypes A and B, of which A is more common and easily recognized by the preying birds. In comparison, the B phenotype is relatively rare or unknown to the bird. It makes sense for the bird to choose to prey on the familiar A phenotype rather than risking its health and survival by ingesting the rare B phenotype. Hence this grants an advantage to the rarer phenotype and increases its chance of survival; whereas the common phenotype perishes and has decreased fitness.

Similarly, the most common example for this type is that of the influenza virus that causes common cold in humans. If a particular common strain of the flu virus infects an individual, after an initial period of infliction, the human body develop a immune response to the virus, and the memory of this response is stored in our system, effectively making us immune to a second infection by the same virus. However, if the flu virus undergoes a spontaneous mutation to evolve into a rare and novel strain, it spreads through the human population easily without any resistance. Hence the rare form has more fitness than the common form. Other examples include:
  • High degree of polymorphisms exhibited by the MHC in the immune system implies a stronger defense against any infections, or disease.
  • Plants with self-incompatibility alleles, where if a new variant emerges, can successfully mate and spread its genes throughout the population.

Positive Frequency-dependent Selection

In contrast to the inversely proportional relationship between fitness and frequency exhibited by the negative selection, the positive frequency-dependent selection exhibits a direct proportion between the fitness and phenotype of an organism. This translates into the fact that the fitness of a phenotype increases as it gets more common, and reduces in case it is rare. This method is used for beneficial purposes by mimicking organisms that exhibit a phenotype similar to other organisms.

In order to understand this concept, consider the concept of aposematism. It occurs in conjugation with warning visual signals in the form of color, sounds, or odor in certain species of animals, which indicate their toxic nature. It advertises the preys harmful and toxic nature to the predator, thereby issuing a cautionary signal to allow them to avoid potential harm. Hence if a predator perceives these signals from a particular prey, it may choose to forgo it in order to save itself from harm. This unique mechanism is exploited by other harmless preys to escape predation, they do so by emulating and mimicking the same warning signal of the harmful species, such that when a predator approaches, it believes that the prey is harmful and hence does not consume it. Hence the commonly seen phenotype that is regarded as harmful helps increase the fitness and survivability of the organism.

The classical example of this type of selection are all the animals that display Batesian and Mullerian mimicry. Batesian mimicry involves the copying of the warning signals of a harmful species by a harmless species, for example, hoverflies (harmless) copy the physical appearance of bees and wasps (harmful); whereas, Mullerian mimicry involves two species of harmful organisms that have the same predators, and hence have evolved to escape them by mimicking each others warning signals, for example, the viceroy and monarch butterflies are both toxic to the predator, and both of them also exhibit similar appearances. Other examples of this type of selection include:
  • The nonvenomous California mountain kingsnake that mimics the venomous Eastern coral snake
  • Striped zorillas or polecats mimic the appearance of skunks

The occurrence of balancing selection is crucial and incredibly important for the purposes of maintaining as well as inducing the genetic diversity in any given population of organisms. This is a concrete way to maintain the survival of species and saving them from extinction, as the loss of genetic variability leads to the inducement of incredible susceptibility and lowered survivability in the particular species. Also, the study of this type of selection will help us understand the mechanisms operating in nature, which can then be applied in suitable biological research for the benefit of mankind.