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A polymorphism is a genetic variant that appears in at least 1% of a population.

Examples: By setting the cutoff at 1%, it excludes spontaneous mutations that may have occurred in — and spread through the descendants of — a single family.
Link to an example

Protein Polymorphisms

All the examples above are of the protein products of alleles. These can be identified by:
Link to description of electrophoresis.

Enzymes are frequently polymorphic. A population may contain two or more variants of an enzyme encoded by a single locus. The variants differ slightly in their amino acid sequence and often this causes them to migrate differently under electrophoresis. By treating the gel with the substrate for the enzyme, its presence can be visualized.

Here is an example (courtesy of Susan McAlpine).

Electrophoresis of tissue extracts from 15 different green treefrogs (Hyla cinerea) reveals 4 allelic versions of the enzyme aconitase (one of the enzymes of the citric acid cycle). The 4 alleles can be distinguished by the speed with which their protein product migrates: The results: Electrophoretic variants of an enzyme occurring in a population are called allozymes.

Restriction Fragment Length Polymorphisms (RFLPs)

Proteins are gene products and so polymorphic versions are simply reflections of allelic differences in the gene; that is, allelic differences in DNA.

Often these changes create new — or abolish old — sites for restriction enzymes to cut the DNA. Digestion with the enzyme then produces DNA fragments of a different length. These can be detected by electrophoresis.

RFLPs are discussed in greater detail in a separate page.
Link to it.
Most* RFLPs are created by a change in a single nucleotide in the gene, and so these are called single nucleotide polymorphisms (SNPs).
(* but not all; link to an example of a RFLP caused by a deletion.).

Single Nucleotide Polymorphisms (SNPs)

Developments in DNA sequencing now make it easy to look for allelic versions of a gene by sequencing samples of the gene taken from different members of a population (or from a heterozygous individual). Alleles whose sequence reveals only a single changed nucleotide are called single nucleotide polymorphisms or SNPs.


Copy Number Polymorphisms (CNPs)

Genetic analysis (using DNA chips and FISH) has revealed another class of human polymorphisms. These copy number polymorphisms are large (thousands of base pairs) duplications or deletions that are found in some people but not in others. On average, one person differs from another by 11 of these. One or more have been found on most chromosomes, and the list is probably incomplete.

While most of this DNA is non-coding, functional genes are embedded in some of it. Example: AMY1, the gene encoding salivary amylase, an enzyme that digests starch. Humans vary in the number of copies of AMY1 in their genome.

In the case of AMY1, the more copies present, the more enzyme that is produced. How a person adapts to a change in gene number for autosomal genes is unknown (in contrast to the way that human females adjust the activity of the genes on their two X chromosomes to match that of males with their solitary X chromosome - Link).

How are polymorphisms useful?

Polymorphism analysis is used:

How do polymorphisms arise and persist?

They arise by mutation.

But what keeps them in the population?

Several factors may maintain polymorphism in a population.

Founder Effect

If a population began with a few individuals — one or more of whom carried a particular allele — that allele may come to be represented in many of the descendants.

In the 1680s Adriaantje Ariens and Gerrit Jansz emigrated from Holland to South Africa, one of them bringing along an allele for the mild metabolic disease porphyria. Today it is estimated that more than 30,000 South Africans carry this allele and, in every case examined, can trace it back to this couple — a remarkable example of the founder effect.

Genetic Drift

An allele may increase — or decrease — in frequency simply through chance. Not every member of the population will become a parent and not every set of parents will produce the same number of offspring.

The effect, called random genetic drift, is particularly strong

Eventually the entire population may become homozygous for the allele or — equally likely — the allele may disappear. Before either of these fates occurs, the allele represents a polymorphism.

Two examples of reduced polymorphism because of genetic drift:

Natural Selection

Copy Number Polymorphisms

The varying number of copies of the AMY1 gene in different human populations appears to have arisen from the evolutionary pressure of the differences in the starch content of their diet [above].

Balanced Polymorphism

In regions of the world (e.g., parts of Africa) where malaria caused by Plasmodium falciparum is common, the allele for sickle-cell hemoglobin is also common. This is because children who inherit are more likely to survive than either homozygote.

Hence the relatively high frequency of the allele in malarial regions.

View the structure of the two alleles and their products.

When natural selection favors heterozygotes over both homozygotes, the result is balanced polymorphism. It accounts for the persistence of an allele even though it is deleterious when homozygous.

Another example: prion proteins

All human populations are polymorphic for the prion protein PrPC. It is encoded by the prion protein gene (PRNP). Two of the alleles have different codons at position 129:

Homozygosity for either allele increases the susceptibility to prion diseases. People who are heterozygous are more resistant.

A study of elderly women who had survived the kuru epidemic of the first half of the 20th century (eating the tissues of the deceased was banned in 1950) showed that 76.7% of them were heterozygotes. This table compares the gene frequencies in this population as well as in a population that never practiced mortuary feasts.

M is the allele encoding the methionine; V the allele encoding valine.

Survivors 0.133 0.767 0.100
Unexposed 0.221 0.514 0.264

A quick calculation will show that the gene pool of the exposed women deviates widely from what would be found if the population were in Hardy-Weinberg equilibrium. In this case, strong mortality selection is the cause. The gene pool of the unexposed population is close to being in Hardy-Weinberg equilibrium.

Here, again, natural selection has favored heterozygotes over both homozygotes (and led to the speculation that cannibalism may have been common earlier in human history) [Link].

Natural vs. Sexual Selection

Balanced polymorphism in Soay sheep.

Hirta is a tiny island in the North Atlantic 100 miles off the northwest coast of Scotland. In 1932 a small (107) population of domestic sheep (Ovis aries) was introduced onto the island from the neighboring island of Soay. Since then these sheep have been allowed to run wild and, since 1985, have been intensively studied.

The sheep have horns and, in males, these play an important role in competition for females. The size of the horns is strongly influenced by a single gene locus, RXFP2, with two alleles: Ho+ and HoP.

You can read about these findings in Johnston, Susan. E., et al., Nature 502, 93–95, 3 October 2013.

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10 February 2024