Genetic Equilibrium: Linkage

Linkage genetic equilibrium

Genetic equilibriumis the tendency for genes located close together on the same chromosome to be inherited together. The farther apart the genes, the less likely it is that they will be passed along together.

The genetic complement of any organismis contained on one or more types of chromosomes. Whether there are only a few chromosomes or many (such as in a diploid organism), each type occurs as a set of two, called homologs.

Each gene at a particular locus, or site, along the chromosome occurs twice in the same cell (except for some loci which only occur on one of the two sex chromosomes), one copy of each homolog. The particular information at each locus may be different because genes can exist in several forms.

An alternative form of a particular gene is called an allele. For example, one of the genes for flower color in pea plans can exist as a white allele or a purple allele.

A given pea plant could have a white allele on one homologous chromosome and a purple allele on the other. Each homologous chromosome, therefore, contains an allele at a locus which may or may not be the same as the allele on its homolog.

During reproduction, this chromosomal material is copied, thereby duplicating the individual genes which lie along the chromosome. During mitosis, a copy of each chromosome is distributed to each of the two new nuclei.

In meiosis, however, during gamete production, the chromosome copies are separated so that only a single chromosome from each pair of homologous chromosomes is distributed to each of four new nuclei.

Before this happens, however, the homologs and their duplicates, called sister chromatids, become aligned. The arms of sister chromatids undergo crossover near the beginning of the first part of meiosis, which results in the exchange of homologous regions of these chromosomes.

The result of this crossing over is that alleles that were once on one homolog are now on the other. In mitosis, genes on the same chromosome exhibit linkage and tend to remain together and be inherited by the daughter cell together; in meiosis, these linked genes can become recombined in new associations so that linkage is partial. Individuals with chromosomes exhibiting these new combinations of alleles are called recombinants.

Discovery of Linkage

Mendelian genetics (named for GregorMendel) predicts a 3:1 phenotypic ratio in a monohybrid cross (a cross involving only one gene having two alleles, one dominant and one recessive) and a 9:3:3:1 phenotypic ratio in a dihybrid cross (a cross involving two genes on different chromosomes, each having two alleles, one dominant and one recessive).

Early in the twentieth century, geneticists began to notice that not all crosses produced offspring in the proportions predicted by Mendel’s law of independent assortment.

Cytologists also discovered that occasionally homologous chromosomes did not look exactly alike. Geneticists used these differences in chromosomes as cytological markers and associated them with genetic markers or alleles with specific effects.

In 1911 T.H.Morgan concluded that during segregation of alleles at meiosis, certain genes tend to remain together because they lie near each other on the same chromosome. The closer genes are located to each other on the chromosome, the greater their tendency to remain linked.

In 1909 chiasmata had been described. Chiasmata represent the locations of exchanges (crossover) between maternal and paternal homologous chromosomes. Morgan hypothesized that partial linkage occurs when two genes on the same chromosome are separated physically from each other by cross-over during meiosis.

Crossover provides new combinations of genes, genes which did not exhibit the linkage relationship in the parents but which were recombined. In these kinds of crosses, the parental phenotypic classes are most frequent in the off-spring, while the recombinant classes occur much less frequently.

Genetic recombination results from physical exchange between homologous chromosomes that have become tightly aligned during meiotic prophase. A chiasma is the site of crossing over and is where homologs have lined up touching each other where they are homologous.

Crossing over itself is the exchange of parts of nonsister chromatids of homologous chromosomes by symmetrical breakage and crosswise rejoining. Two papers providing convincing evidence of this were published within weeks of each other in 1930.

Harriet Creighton and Barbara Mc Clintock worked with corn (Zeamays). They studied individuals in which the two copies of chromosome 9 had a strikingly different appearance.

They studied two loci on chromosome 9, one affecting seed color (colored and colorless, dominant and recessive, respectively) and the other affecting endosperm composition (waxy or starchy, dominant and recessive, respectively). One homolog was dominant for both traits (colored and waxy) and lacked the knob and the extension. Plants with these two homologs of chromosome 9 had colored, waxy seeds.

Recombinant offspring would have either colored and starchy seeds or colorless and waxy seeds and their copies of chromosome extension but no knob. Off-spring that were like the parents showed no change in chromosome structure. This provided visual evidence that crossover had occurred.

Genetic Maps

The frequency of crossover can be used to construct a genetic map. The more closely linked genes are, the less frequently crossing over will take place between them. The recombinants will occur much less frequently than when linked genes are more widely separated.

With widely separated genes, the chances of double crossovers increases, so that the recombination frequency may actually underestimate the crossover frequency and, hence, the map distance.

The map distance is a relative distance based on the percent of recombination and is not a precise physical distance. The presence of a chiasma in one region often prevents the occurrence of a second chiasma nearby. This phenomenon is called interference.

In many large, randomly mating natural populations, the genotype frequencies at each locus will typically be found at a mathematically determined equilibrium. In a single generation of random mating, unlinked loci separately attain equilibrium of genotype frequencies.

This is not true of linked loci. If loci are unlinked, equilibrium occurs very rapidly, but if the loci are on the same chromosome, the speed of approach to equilibrium is proportional to the map distance between them.

Once equilibriumis attained, repulsion and coupling gamete frequencies do not depend on the degree of linkage. Another way of saying this is that the characters produced by alleles at linked loci show no particular association in an equilibrium population.

When characters happen to be associated in a population, the association may form because alleles at separate loci that are in genetic disequilibrium result from recent population immigrations. They may also be the result of selection for certain allelic combinations. Like dominance, linkage can be confirmed only in controlled breeding experiments.


Mutations are the ultimate source of variation. In populations, mutant alleles may accumulate over time because they are recessive to the normal allele.

Recessive lethal alleles, as well as beneficial alleles, persist in populations because recessive alleles are hidden when in the heterozygous state (that is, in individuals who have one normal, dominant allele and one mutant, recessive allele). It is only when the mutant becomes widely distributed in the population that they are revealed.

With ten loci and four alleles at each locus, ten billion different possible genotypes will occur with equal frequency if all the alleles occur with equal frequency and segregate independently.

This describes a state of linkage equilibrium. In a natural population, however, these conditions are rarely met. The probability is that some genotypes will be more common than others, even if the allele frequencies are all the same.

Diploid organisms typically have tens of thousands of gene loci. Because they have only a small number of chromosomes, usually less than forty, many loci lie on the same chromosome. The genotypes are highly biased toward already existing combinations.

This does not alter the theoretical possibilities of particular genotypes, only the probability of their occurrence. It does ensure that variation is present in the population for adaptability to changing conditions, while maintaining large numbers of individuals that are adapted to existing conditions.

Functions of Linkage

Linked genes may control very different functions. For example, enzymes vary depending on climate. Northern species may possess an enzyme which functions at a lower temperature than the variant of the southern species.

Linked to the gene which controls this highly adaptive allele may be an allele of another gene whose adaptive value is lower or neutral. This less adapted allele hitchhikes on the chromosome with the adaptive allele.

Linkage disequilibrium is decreased by recombination. The maintenance of favorable allelic combinations in linkage disequilibrium is enhanced by reducing recombination between the loci involved. This is achieved by inversions and translocations that include the loci involved.

The genes included in these in the translocated or inverted region are sometimes called supergenes, because of their strong tendency to be inherited as a large unit of many genes. Inversions and translocation do not completely inhibit crossover in the regions involved, but they do reduce it.

They also reduce the occurrence of recombinant chromosomes, because if a crossover does occur in one of these regions, most of their resulting recombinant chromosomes are either lethal or cause varying levels of sterility.

Whenever linkage disequilibrium is favored by natural selection, chromosomal rearrangements increasing linkage among loci will also be favored by natural selection.