A polymorphism is a genetic variant that appears in at least 1% of a population.
By setting the cutoff at 1%, it excludes spontaneous mutations that may have occurred in - and spread through the descendants of - a single family.
All the examples above are of the protein products of alleles. These can be identified by:
- serology; that is, using antibodies to detect the different versions of the protein. (Antibodies caused the clumping of the red blood cells in this View)
- electrophoresis; if amino acid changes in the protein alter its net electrical charge, it will migrate more or less rapidly in an electrical field.
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:
- Fast (F)
- moderately fast (E)
- medium (M)
- slow (S)
Electrophoretic variants of an enzyme occurring in a population are called allozymes.
- Eight frogs (#2, 3, 4, 6, 7, 9, 12, and 14) were homozygous for allele M.
- Frog #8 was homozygous for allele E.
- Three frogs (#1, 11, 15) are heterozygous for the M and S alleles.
- Two (#5, 13) were heterozygous for M and E.
- Frog #10 was heterozygous for M and F.
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.
Most* RFLPs are created by a change in a single nucleotide in the gene, and so these are called 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.
Polymorphism analysis is used:
- can occur in noncoding parts of the gene so they would not be seen in the protein product.
- might not alter the cutting site for any known restriction enzymes so they would not be seen by RFLP analysis.
Comparing the DNA of chromosome 22 from only 7 different people (northern Europeans) revealed 2,730 SNPs. As of mid-summer 2000, over 350,000 SNPs had been identified across the human genome.
- in tissue typing; in order to find the best match between the donor, e.g., of a kidney, and the recipient.
- finding disease genes. Example: the gene for Huntington's disease was located when the presence of the disease was found to be linked to a RFLP whose location on the chromosome was known.
- in population studies, for example
- Assessing the degree of genetic diversity in a population.
- The McAlpine study, which produced the photo above, found that the heterozygous frogs were more successful breeders than homozygous ones.
- A search for polymorphisms in elephant seals and cheetahs has revealed that they have little or none. (details below).
- Determining whether two populations represent separate species or races of the same species. This is often critical to applying laws protecting endangered species.
- Tracking migration patterns of a species (e.g., whales).
But what keeps them in the population?
Several factors may maintain polymorphism in a population.
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 Ariaantje and Gerrit Jansz emigrated from Holland to South Africa, one of them bringing along an allele for the mild metabolic disease porphyria. Today more than 30000 South Africans carry this allele and, in every case examined, can trace it back to this couple - a remarkable example of the founder effect.
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.
- in small populations (e.g., 100 breeding pairs or fewer);
- when the gene is neutral; that is, is neither helpful nor deleterious.
Two examples of reduced polymorphism because of genetic drift:
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
- By 1900 hunting of the northern elephant seal off the Pacific coast had reduced its population to only 20 survivors. Since hunting ended, the population has rebounded from this population bottleneck to some 100,000 animals today. However, these animals are homozygous at every one of the gene loci that have been examined.
- Cheetahs, the fastest of the land animals, seem to have passed through a similar period of small population size with its accompanying genetic drift. Examination of 52 different loci has failed to reveal any polymorphisms; that is, these animals are homozygous at all 52 loci. The lack of genetic variability is so profound that cheetahs will accept skin grafts from each other just as identical twins (and inbred mouse strains) do. Whether a population with such little genetic diversity can continue to adapt to a changing environment remains to be seen.
are more likely to survive that either homozygote.
- one gene for the "normal" beta chain of hemoglobin and
- one sickle gene
- Children homozygous for the sickle allele die young from sickle-cell disease but
- children homozygous for the "normal" beta chain are far more susceptible to illness and death from falciparum malaria than are heterozygotes.
Hence the relatively high frequency of the allele in malarial regions.
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.
22 January 2001