Balancing selection refers to a number of
selective processes by which multiple
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
s (different versions of a
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
) are actively maintained in the
gene pool of a
population
Population typically refers to the number of people in a single area, whether it be a city or town, region, country, continent, or the world. Governments typically quantify the size of the resident population within their jurisdiction using a ...
at frequencies larger than expected from
genetic drift
Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.
Genetic drift may cause gene variants to disappear completely and there ...
alone. Balancing selection is rare compared to purifying selection. It can occur by various mechanisms, in particular, when the
heterozygotes
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
for the alleles under consideration have a higher
fitness than the
homozygote
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
. In this way
genetic polymorphism
A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to gen ...
is conserved.
Evidence for balancing selection can be found in the number of alleles in a population which are maintained above mutation rate frequencies. All modern research has shown that this significant genetic variation is ubiquitous in
panmictic populations.
There are several mechanisms (which are not exclusive within any given population) by which balancing selection works to maintain polymorphism. The two major and most studied are heterozygote advantage and frequency-dependent selection.
Mechanisms
Heterozygote advantage
![Malaria versus sickle-cell trait distributions](https://upload.wikimedia.org/wikipedia/commons/1/10/Malaria_versus_sickle-cell_trait_distributions.png)
In
heterozygote advantage
A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype. Loci exhibiting heterozygote advantage are a small minority of ...
, or ''heterotic balancing selection'', an individual who is heterozygous at a particular gene
locus
Locus (plural loci) is Latin for "place". It may refer to:
Entertainment
* Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front
* ''Locus'' (magazine), science fiction and fantasy magazine
** ''Locus Award' ...
has a greater
fitness than a homozygous individual. Polymorphisms maintained by this mechanism are ''balanced polymorphisms''. Due to unexpected high frequencies of heterozygotes, and an elevated level of heterozygote fitness, heterozygotic advantage may also be called "overdominance" in some literature.
A well-studied case is that of
sickle cell anemia
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
in humans, a
hereditary disease that damages
red blood cells. Sickle cell anemia is caused by the inheritance of an allele (HgbS) of the
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
from both parents. In such individuals, the hemoglobin in red blood cells is extremely sensitive to oxygen deprivation, which results in shorter life expectancy.
A person who inherits the sickle cell gene from one parent and a normal hemoglobin allele (HgbA) from the other, has a normal life expectancy. However, these heterozygote individuals, known as ''carriers'' of the
sickle cell trait
Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that all ...
, may suffer problems from time to time.
The heterozygote is resistant to the
malarial parasite which kills a large number of people each year. This is an example of balancing selection between the fierce selection against homozygous sickle-cell sufferers, and the selection against the standard HgbA homozygotes by malaria. The heterozygote has a permanent advantage (a higher fitness) wherever malaria exists. Maintenance of the HgbS allele through positive selection is supported by significant evidence that heterozygotes have decreased fitness in regions where malaria is not prevalent. In Surinam, for example, the allele is maintained in the gene pools of descendants of African slaves, as the Surinam suffers from perennial malaria outbreaks. Curacao, however, which also has a significant population of individuals descending from African slaves, lacks the presence of widespread malaria, and therefore also lacks the selective pressure to maintain the HgbS allele. In Curacao, the HgbS allele has decreased in frequency over the past 300 years, and will eventually be lost from the gene pool due to
heterozygote disadvantage.
Frequency-dependent selection
Frequency-dependent selection occurs when the fitness of a phenotype is dependent on its frequency relative to other phenotypes in a given population. In ''positive frequency-dependent selection'' the fitness of a phenotype increases as it becomes more common. In ''negative frequency-dependent selection'' the fitness of a phenotype decreases as it becomes more common. For example, in
prey switching Prey switching is frequency-dependent predation, where the predator preferentially consumes the most common type of prey. The phenomenon has also been described as apostatic selection, however the two terms are generally used to describe different ...
, rare morphs of prey are actually fitter due to predators concentrating on the more frequent morphs. As predation drives the demographic frequencies of the common morph of prey down, the once rare morph of prey becomes the more common morph. Thus, the morph of advantage now is the morph of disadvantage. This may lead to boom and bust cycles of prey morphs. Host-parasite interactions may also drive negative frequency-dependent selection, in alignment with the Red Queen hypothesis. For example, parasitism of freshwater New Zealand snail (''Potamopyrgus antipodarum'') by the trematode ''Microphallus sp.'' results in decreasing frequencies of the most commonly hosted genotypes across several generations. The more common a genotype became in a generation, the more vulnerable to parasitism by ''Microphallus sp.'' it became. Note that in these examples that no one phenotypic morph, nor one genotype is entirely extinguished from a population, nor is one phenotypic morph nor genotype selected for fixation. Thus, polymorphism is maintained by negative frequency-dependent selection.
Fitness varies in time and space
The fitness of a genotype may vary greatly between larval and adult stages, or between parts of a habitat range. Variation over time, unlike variation over space, is not in itself enough to maintain multiple types, because in general the type with the highest
geometric mean fitness will take over, but there are a number of mechanisms that make stable coexistence possible.
More complex examples
Species in their natural habitat are often far more complex than the typical textbook examples.
Grove snail
The grove snail, ''
Cepaea nemoralis
The grove snail, brown-lipped snail or Lemon snail (''Cepaea nemoralis'') is a species of air-breathing land snail, a terrestrial pulmonate gastropod mollusc. MolluscaBase eds. (2020). MolluscaBase. Cepaea nemoralis (Linnaeus, 1758). Accessed thr ...
'', is famous for the rich polymorphism of its shell. The system is controlled by a series of
multiple alleles
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chrom ...
. Unbanded is the top dominant trait, and the forms of banding are controlled by modifier genes (see
epistasis).
In England the snail is regularly preyed upon by the
song thrush ''Turdus philomelos'', which breaks them open on ''thrush anvils'' (large stones). Here fragments accumulate, permitting researchers to analyse the snails taken. The thrushes hunt by sight, and capture selectively those forms which match the habitat ''least well''. Snail colonies are found in woodland, hedgerows and grassland, and the predation determines the proportion of phenotypes (morphs) found in each colony.
A second kind of selection also operates on the snail, whereby certain heterozygotes have a physiological advantage over the homozygotes. Thirdly,
apostatic selection
Apostatic selection is a form of negative frequency-dependent selection. It describes the survival of individual prey animals that are different (through mutation) from their species in a way that makes it more likely for them to be ignored by the ...
is likely, with the birds preferentially taking the most common morph. This is the 'search pattern' effect, where a predominantly visual predator persists in targeting the morph which gave a good result, even though other morphs are available.
The polymorphism survives in almost all habitats, though the proportions of morphs varies considerably. The alleles controlling the polymorphism form a
supergene with linkage so close as to be nearly absolute. This control saves the population from a high proportion of undesirable recombinants.
In this species predation by birds appears to be the main (but not the only) selective force driving the polymorphism. The snails live on heterogeneous backgrounds, and thrush are adept at detecting poor matches. The inheritance of physiological and cryptic diversity is preserved also by heterozygous advantage in the supergene. Recent work has included the effect of shell colour on thermoregulation, and a wider selection of possible genetic influences is also considered.
Chromosome polymorphism in ''Drosophila''
In the 1930s
Theodosius Dobzhansky
Theodosius Grigorievich Dobzhansky (russian: Феодо́сий Григо́рьевич Добржа́нский; uk, Теодо́сій Григо́рович Добржа́нський; January 25, 1900 – December 18, 1975) was a prominent ...
and his co-workers collected ''
Drosophila pseudoobscura'' and ''
D. persimilis'' from wild populations in
California
California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the m ...
and neighbouring states. Using
Painter's technique, they studied the
polytene chromosome
Polytene chromosomes are large chromosomes which have thousands of DNA strands. They provide a high level of function in certain tissues such as salivary glands of insects.
Polytene chromosomes were first reported by E.G.Balbiani in 1881. P ...
s and discovered that all the wild populations were polymorphic for
chromosomal inversions. All the flies look alike whatever inversions they carry, so this is an example of a cryptic polymorphism. Evidence accumulated to show that natural selection was responsible:
# Values for heterozygote inversions of the third chromosome were often much higher than they should be under the null assumption: if no advantage for any form the number of heterozygotes should conform to N
s (number in sample) = p
2+2pq+q
2 where 2pq is the number of heterozygotes (see
Hardy–Weinberg equilibrium).
# Using a method invented by L'Heretier and Teissier, Dobzhansky bred populations in ''population cages'', which enabled feeding, breeding and sampling whilst preventing escape. This had the benefit of eliminating
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
as a possible explanation of the results. Stocks containing inversions at a known initial frequency can be maintained in controlled conditions. It was found that the various chromosome types do not fluctuate at random, as they would if selectively neutral, but adjust to certain frequencies at which they become stabilised.
# Different proportions of chromosome morphs were found in different areas. There is, for example, a polymorph-ratio
cline
Cline may refer to:
Science
* Cline (biology), a measurable gradient in a single trait in a species across its geographical range
* Cline (hydrology), a fluid layer with a property that varies
* Cline (mathematics) or generalised circle, a circl ...
in ''
D. robusta'' along an transect near
Gatlinburg,
TN passing from to 4,000 feet. Also, the same areas sampled at different times of year yielded significant differences in the proportions of forms. This indicates a regular cycle of changes which adjust the population to the seasonal conditions. For these results selection is by far the most likely explanation.
# Lastly, morphs cannot be maintained at the high levels found simply by mutation, nor is drift a possible explanation when population numbers are high.
By 1951 Dobzhansky was persuaded that the chromosome morphs were being maintained in the population by the selective advantage of the heterozygotes, as with most polymorphisms.
[Ford E.B. 1975. ''Ecological genetics''. 4th ed. Chapman & Hall, London.]
See also
*
Directional selection
In population genetics, directional selection, is a mode of negative natural selection in which an extreme phenotype is favored over other phenotypes, causing the allele frequency to shift over time in the direction of that phenotype. Under dir ...
*
Disruptive selection
*
Stabilizing selection
Stabilizing selection (not to be confused with negative or purifying selection) is a type of natural selection in which the population mean stabilizes on a particular non-extreme trait value. This is thought to be the most common mechanism of a ...
*
Fluctuating selection
Fluctuating selection is a mode of natural selection characterized by the fluctuation of the direction of selection on a given phenotype over a relatively brief period of evolutionary time. For example, a species of plant may come in two varieties ...
References
{{DEFAULTSORT:Balancing Selection
Selection