In this article we will discuss about the mechanisms that decrease and increase genetic variation.

Mechanisms that Decrease Genetic Variation:

i. Natural Selection:

Some types of organisms within a population leave more offspring than others. Over time, the frequency of the more prolific type will increase. The difference in reproductive capability is called natural selection. Natural selection is the only mechanism of adaptive evolution; it is defined as differential reproductive success of pre­existing classes of genetic variants in the gene pool.

The most common action of natural selection is to remove unfit variants as they arise via mutation. In other words, natural selection usually prevents new alleles from increasing its frequency. This led a famous evolutionist, George Williams, to say “Evolution proceeds in spite of natural selection.”

Natural selection can maintain or deplete genetic variation depending on how it acts. When selection acts to weed out deleterious alleles, or causes an allele to sweep to fixation, it depletes genetic variation. When heterozygotes are fit than either of the homozygotes, however, selection causes genetic variation to be maintained.

This is called balancing selection. An example of this is the maintenance of sickle-cell alleles in human populations subject to malaria. Variation at a single locus determines whether red blood cells are shaped normally or sickled. If a human has two alleles for sickle- cell, he/she develops anemia — the shape of sickle-cells precludes them carrying normal levels of oxygen.

However, heterozygotes that have one copy of the sickle-cell allele, coupled with one normal allele enjoy some resistance to malaria —the shape of sickled cells makes it harder for the plasmodia (malaria causing agents) to enter the cell. Thus, individuals homozygous for the normal allele suffer more malaria than heterozygotes.

Individuals homozygous for the sickle- cell are anemic. Heterozygotes have the highest fitness of these three types. Heterozygotes pass on both sickle- cell and normal alleles to the next generation. Thus, neither allele can be eliminated from the gene pool. The sickle-cell allele is at its highest frequency in regions of Africa where malaria is most pervasive.

Balancing selection is rare in natural populations. Only a handful of other cases beside the sickle-cell example have been found. At one time population geneticists thought balancing selection could be a general explanation for the levels of genetic variation found in natural populations.

That is no longer the case. Balancing selection is only rarely found in natural populations. And, there are theoretical reasons why natural selection cannot maintain polymorphisms at several loci via balancing selection.

Individuals are selected. Dark colored moths had a higher reproductive success because light colored moths suffered a higher predation rate. The decline of light colored alleles was caused by light colored individuals being removed from the gene pool (selected against). Individual organisms either reproduce or fail to reproduce and are hence the unit of selection.

One way alleles can change in frequency is to be housed in organisms with different reproductive rates. Genes are not the unit of selection (because their success depends on the organism’s other genes as well); neither are groups of organisms a unit of selection. There are some exceptions to this “rule” but it is a good generalization.

Organisms do not perform any behaviours that are for the good of their species. An individual organism competes primarily with others of its own species for its reproductive success. Natural selection favors selfish behaviour because any truly altruistic act increases the recipient’s reproductive success while lowering the donors.

Altruists would disappear from a population as the non- altruists would reap the benefits, but not pay the costs, of altruistic acts. Many behaviours appear altruistic. Biologists, however, can demonstrate that these behaviours are only apparently altruistic. Cooperating with or helping other organisms is often the most selfish strategy for an animal. This is called reciprocal altruism.

A good example of this is blood sharing in vampire bats. In these bats, those who are lucky enough to find a meal will often share part of it with an unsuccessful bat by regurgitating some blood into the other’s mouth.

Biologists have found that these bats form bonds with partners and help each other out when the other is needy. If a bat is found to be a “cheater,” his partner will abandon him. The bats are thus not helping each other altruistically; they form pacts that are mutually beneficial.

Helping closely related organisms can appear altruistic; but this is also a selfish behaviour. Reproductive success (fitness) has two components; direct fitness and indirect fitness. Direct fitness is a measure of how many alleles, on average, a genotype contributes to the subsequent generation’s gene pool by reproducing.

Indirect fitness is a measure of how many alleles identical to its own it helps to enter the gene pool. Direct fitness plus indirect fitness is inclusive fitness. J. B. S. Haldane once remarked he would gladly drown, if by doing so he saved two siblings or eight cousins. Each of his siblings would share one half his alleles; his cousins, one eighth. They could potentially add as many of his alleles to the gene pool as he could.

Natural selection favors traits or behaviours that increase a genotype’s inclusive fitness. Closely related organisms share many of the same alleles. In diploid species, siblings share on average at least 50% of their alleles. The percentage is higher if the parents are related. So, helping close relatives to reproduce gets an organism’s own alleles better represented in the gene pool.

The benefit of helping relatives increases dramatically in highly inbred species. In some cases, organisms will completely forgo reproducing and only help their relatives reproduce. Ants, and other eusocial insects, have sterile castes that only serve the queen and assist her reproductive efforts. The sterile workers are reproducing by proxy.

The words selfish and altruistic have connotations in everyday use that biologists do not intend. Selfish simply means behaving in such a way that one’s own inclusive fitness is maximized; altruistic means behaving in such a way that another’s fitness is increased at the expense of ones’ own. Use of the words selfish and altruistic is not meant to imply that organisms consciously understand their motives.

The opportunity for natural selection to operate does not induce genetic variation to appear — selection only distinguishes between existing variants. Variation is not possible along every imaginable axis, so all possible adaptive solutions are not open to populations. To pick a somewhat ridiculous example, a steel shelled turtle might be an improvement over regular turtles.

Turtles are killed quite a bit by cars these days because when confronted with danger, they retreat into their shells — this is not a great strategy against a two ton automobile. However, there is no variation in metal content of shells, so it would not be possible to select for a steel shelled turtle.

Here is a second example of natural selection. Geospiza fortis lives on the Galapagos islands along with fourteen other finch species. It feeds on the seeds of the plant Tribulus cistoides, specializing on the smaller seeds. Another species, G. Magnirostris, has a larger beak and specializes on the larger seeds.

The health of these bird populations depends on seed production. Seed production, in turn, depends on the arrival of wet season. In 1977, there was a drought. Rainfall was well below normal and fewer seeds were produced. As the season progressed, the G. fortis population depleted the supply of small seeds. Eventually, only larger seeds remained.

Most of the finches starved; the population plummeted from about twelve hundred birds to less than two hundred. Peter Grant, who had been studying these finches, noted that larger beaked birds fared better than smaller beaked ones. These larger birds had offspring with correspondingly large beaks.

Thus, there was an increase in the proportion of large beaked birds in the population the next generation. To prove that the change in bill size in Geospiza fortis was an evolutionary change, Grant had to show that differences in bill size were at least partially genetically based.

He did so by crossing finches of various beak sizes and showing that a finch’s beak size was influenced by its parent’s genes. Large beaked birds had large beaked offspring; beak size was not due to environmental differences (in parental care, for example).

Natural selection may not lead a population to have the optimal set of traits. In any population, there would be a certain combination of possible alleles that would produce the optimal set of traits (the global optimum); but there are other sets of alleles that would yield a population almost as adapted (local optima).

Transition from a local optimum to the global optimum may be hindered or forbidden because the population would have to pass through less adaptive states to make the transition. Natural selection only works to bring populations to the nearest optimal point. This idea is Sewall Wright’s adaptive landscape. This is one of the most influential models that shape how evolutionary biologists view evolution.

Natural selection does not have any foresight. It only allows organisms to adapt to their current environment. Structures or behaviours do not evolve for future utility. An organism adapts to its environment at each stage of its evolution. As the environment changes, new traits may be selected for.

Large changes in populations are the result of cumulative natural selection. Changes are introduced into the population by mutation; the small minority of these changes that result in a greater reproductive output of their bearers are amplified in frequency by selection.

Complex traits must evolve through viable intermediates. For many traits, it initially seems unlikely that intermediates would be viable. What good is half a wing? Half a wing may be no good for flying, but it may be useful in other ways. Feathers are thought to have evolved as insulation (ever worn a down jacket?) and/or as a way to trap insects.

Later, proto-birds may have learned to glide when leaping from tree to tree. Eventually, the feathers that originally served as insulation now became co-opted for use in flight. A trait’s current utility is not always indicative of its past utility. It can evolve for one purpose, and be used later for another.

A trait evolved for its current utility is an adaptation; one that evolved for another utility is an exaptation. An example of an exaptation is a penguin’s wing. Penguins evolved from flying ancestors; now they are flightless and use their wings for swimming.

ii. Sexual Selection:

In many species, males develop prominent secondary sexual characteristics. A few often cited examples are the peacock’s tail; coloring and patterns in male birds in general, voice calls in frogs and flashes in fireflies. Many of these traits are a liability from the standpoint of survival. Any ostentatious trait or noisy, attention getting behaviour will alert predators as well as potential mates. How then could natural selection favor these traits?

Natural selection can be broken down into many components, of which survival is only one. Sexual attractiveness is a very important component of selection, so much so that biologists use the term sexual selection when they talk about this subset of natural selection.

Sexual Selection is natural selection operating on factors that contribute to an organism’s mating success. Traits that are a liability to survival can evolve when the sexual attractiveness of a trait outweighs the liability incurred for survival. A male who lives a short time, but produces many offspring is much more successful than a long lived one that produces few.

The former’s genes will eventually dominate the gene pool of his species. In many species, especially polygynous species where only a few males monopolize all the females, sexual selection has caused pronounced sexual dimorphism.

In these species males compete against other males for mates. The competition can be either direct or mediated by female choice. In species where females choose, males compete by displaying striking phenotypic characteristics and/or performing elaborate courtship behaviours.

The females then mate with the males that most interest them, usually the ones with the most outlandish displays. There are many competing theories as to why females are attracted to these displays.

The good genes model states that the display indicates some component of male fitness. A good genes advocate would say that bright coloring in male birds indicates a lack of parasites. The females are cueing on some signal that is correlated with some other component of viability.

Selection for good genes can be seen in sticklebacks. In these fish, males have red coloration on their sides. Milinski and Bakker showed that intensity of color was correlated to both parasite load and sexual attractiveness. Females preferred redder males. The redness indicated that he was carrying fewer parasites.

Evolution can get stuck in a positive feedback loop. Another model to explain secondary sexual characteristics is called the runaway sexual selection model. R. A. Fisher proposed that females may have an innate preference for some male trait before it appears in a population.

Females would then mate with male carriers when the trait appears. The offspring of these matings have the genes for both the trait and the preference for the trait. As a result, the process snowballs until natural selection brings it into check. Suppose that female birds prefer males with longer than average tail feathers.

Mutant males with longer than average feathers will produce more offspring than the short feathered males. In the next generation, average tail length will increase. As the generations progress, feather length will increase because females do not prefer a specific length tail, but a longer than average tail.

Eventually tail length will increase to the point where the liability to survival is matched by the sexual attractiveness of the trait and an equilibrium will be established. Note that in many exotic birds male plumage is often very showy and many species do in fact have males with greatly elongated feathers. In some cases these feathers are shed after the breeding season.

None of the above models are mutually exclusive. There are millions of sexually dimorphic species on this planet and the forms of sexual selection probably vary amongst them.

Mechanisms that Increase Genetic Variation:

i. Mutation:

The cellular machinery that copies DNA sometimes makes mistakes. These mistakes alter the sequence of a gene. This is called a mutation. There are many kinds of mutations. A point mutation is a mutation in which one “letter” of the genetic code is changed to another. Lengths of DNA can also be deleted or inserted in a gene; these are also mutations. Finally, genes or parts of genes can become inverted or duplicated.

Typical rates of mutation are between 10-10and 10-12 mutations per base pair of DNA per generation.

Most mutations are thought to be neutral with regards to fitness. Only a small portion of the genome of eukaryotes contains coding segments. And although some non-coding DNA is involved in gene regulation or other cellular functions, it is probable that most base changes would have no fitness consequence.

Most mutations that have any phenotypic effect are deleterious. Mutations that result in amino acid substitutions can change the shape of a protein, potentially changing or eliminating its function. This can lead to inadequacies in biochemical pathways or interfere with the process of development.

Organisms are sufficiently integrated that most random changes will not produce a fitness benefit. Only a very small percentage of mutations are beneficial. The ratio of neutral to deleterious to beneficial mutations is unknown and probably varies with respect to details of the locus in question and environment.

Mutation limits the rate of evolution. The rate of evolution can be expressed in terms of nucleotide substitutions in a lineage per generation. Substitution is the replacement of an allele by another in a population.

This is a two-step process- First a mutation occurs in an individual, creating a new allele. This allele subsequently increases in frequency to fixation in the population. The rate of evolution is k = 2Nvu (in diploids) where k is nucleotide substitutions, N is the effective population size, v is the rate of mutation and u is the proportion of mutants that eventually fix in the population.

Mutation need not be limiting over short time spans. The rate of evolution expressed above is given as a steady state equation; it assumes the system is at equilibrium. Given the time frames for a single mutant to fix, it is unclear if populations are ever at equilibrium. A change in environment can cause previously neutral alleles to have selective values; in the short term evolution can run on “stored” variation and thus is independent of mutation rate.

Other mechanisms can also contribute selectable variation. Recombination creates new combinations of alleles (or new alleles) by joining sequences with separate microevolutionary histories within a population. Gene flow can also supply the gene pool with variants. Of course, the ultimate source of these variants is mutation.

ii. Mutant Alleles:

Mutation creates new alleles. Each new allele enters the gene pool as a single copy amongst many. Most are lost from the gene pool, the organism carrying them fails to reproduce, or reproduces but does not pass on that particular allele. A mutant’s fate is shared with the genetic background it appears in.

A new allele will initially be linked to other loci in its genetic background, even loci on other chromosomes. If the allele increases in frequency in the population, initially it will be paired with other alleles at that locus—the new allele will primarily be carried in individuals heterozygous for that locus.

The chance of it being paired with itself is low until it reaches intermediate frequency. If the allele is recessive, its effect won’t be seen in any individual until a homozygote is formed. The eventual fate of the allele depends on whether it is neutral, deleterious or beneficial.

iii. Neutral Alleles:

Most neutral alleles are lost soon after they appear. The average time (in generations) until loss of a neutral allele is 2(Ne/N) 1n (2N) where N is the effective population size (the number of individuals contributing to the next generation’s gene pool) and N is the total population size.

Only a small percentage of alleles fix. Fixation is the process of an allele increasing to a frequency at or near one. The probability of a neutral allele fixing in a population is equal to its frequency. For a new mutant in a diploid population, this frequency is 1/2N.

If mutations are neutral with respect to Fitness, the rate of substitution (k) is equal to the rate of mutation (v). This does not mean every new mutant eventually reaches fixation. Alleles are added to the gene pool by mutation at the same rate they are lost to drift. For neutral alleles that do fix, it takes an average of 4N generations to do so.

However, at equilibrium there are multiple alleles segregating in the population. In small populations, few mutations appear each generation. The ones that fix do so quickly relative to large populations. In large populations, more mutants appear over the generations. But, the ones that fix take much longer to do so. Thus, the rate of neutral evolution (in substitutions per generation) is independent of population size.

The rate of mutation determines the level of heterozygosity at a locus according to the neutral theory. Heterozygosity is simply the proportion of the population that is heterozygous. Equilibrium heterozygosity is given as H = 4Nv/ [4Nv+1 ] (for diploid populations). H can vary from a very small number to almost one.

In small populations, H is small (because the equation is approximately a very small number divided by one). In (biologically unrealistically) large populations, heterozygosity approaches one (because the equation is approximately a large number divided by itself).

Directly testing this model is difficult because N and v can only be estimated for most natural populations. But, heterozygosities are believed to be too low to be described by a strictly neutral model. Solutions offered by neutralists for this discrepancy include hypothesizing that natural populations may not be at equilibrium.

At equilibrium there should be a few alleles at intermediate frequency and many at very low frequencies. This is the Ewens- Watterson distribution. New alleles enter a population every generation, most remain at low frequency until they are lost. A few drift to intermediate frequencies, a very few drift all the way to fixation.

In Drosophila pseudoobscura, the protein Xanthine dehydrogenase (Xdh) has many variants. In a single population, Keith, et. al., found that 59 of 96 proteins were of one type, two others were represented ten and nine times and nine other types were present singly or in low numbers.

iv. Deleterious Alleles:

Deleterious mutants are selected against but remain at low frequency in the gene pool. In diploids, a deleterious recessive mutant may increase in frequency due to drift. Selection cannot see it when it is masked by a dominant allele. Many disease causing alleles remain at low frequency for this reason.

People who are carriers do not suffer the negative effect of the allele. Unless they mate with another carrier, the allele may simply continue to be passed on. Deleterious alleles also remain in populations at a low frequency due to a balance between recurrent mutation and selection. This is called the mutation load.

v. Beneficial Alleles:

Most new mutants are lost, even beneficial ones. Wright calculated that the probability of fixation of a beneficial allele is 2s. (This assumes a large population size, a small fitness benefit, and that heterozygotes have an intermediate fitness. A benefit of 2s yields an overall rate of evolution- k=4Nvs where v is the mutation rate to beneficial alleles).

An allele that conferred a one percent increase in fitness only has a two percent chance of fixing. The probability of fixation of beneficial type of mutant is boosted by recurrent mutation. The beneficial mutant may be lost several times, but eventually it will arise and stick in a population. (Recall that even deleterious mutants recur in a population.)

Directional selection depletes genetic variation at the selected locus as the fitter allele sweeps to fixation. Sequences linked to the selected allele also increase in frequency due to hitchhiking. The lower the rate of recombination, the larger the window of sequence that hitchhikes. Begun and Aquadro compared the level of nucleotide polymorphism within and between species with the rate of recombination at a locus.

Low levels of nucleotide polymorphism within species coincided with low rates of recombination. This could be explained by molecular mechanisms if recombination itself was mutagenic. In this case, recombination with also be correlated with nucleotide divergence between species.

But, the level of sequence divergence did not correlate with the rate of recombination. Thus, they inferred that selection was the cause. The correlation between recombination and nucleotide polymorphism leaves the conclusion that selective sweeps occur often enough to leave an imprint on the level of genetic variation in natural populations.

One example of a beneficial mutation comes from the mosquito Culex pipiens. In this organism, a gene that was involved with breaking down organophosphates – common insecticide ingredients -became duplicated. Progeny of the organism with this mutation quickly swept across the worldwide mosquito population.

There are numerous examples of insects developing resistance to chemicals, especially DDT which was once heavily used in this country. And, most importantly, even though “good” mutations happen much less frequently than “bad” ones, organisms with “good” mutations thrive while organisms with “bad” ones die out.

If beneficial mutants arise infrequently, the only fitness differences in a population will be due to new deleterious mutants and the deleterious recessives. Selection will simply be weeding out unfit variants. Only occasionally will a beneficial allele be sweeping through a population.

The general lack of large fitness differences segregating in natural populations argues that beneficial mutants do indeed arise infrequently. However, the impact of a beneficial mutant on the level of variation at a locus can be large and lasting. It takes many generations for a locus to regain appreciable levels of heterozygosity following a selective sweep.