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"Biochemical polymorphism" - Color Atlas of Genetics, Eberhard Passarge
Biochemical polymorphism is detected by
laboratory methods. It results from individual
differences in the sequences of nucleotide bases
of DNA. If a difference leads to a change in a
codon, a different amino acid may be incorporated
at the corresponding site of the protein.
This can be demonstrated by analyzing the gene
Subtle differences in the many biochemical reactions
between individuals was recognized
early last century as the basis of genetic individuality
by Archibald Garrod (Bearn, 1993).
A. Recognition of polymorphism by means of gel electrophoresis
Polymorphism of a protein (gene product) can
be demonstrated by gel electrophoresis when
one variant form differs from the others by the
presence of an amino acid with a different electric
charge. In this case, the allelic forms of the
gene product can be distinguished owing to
their different speeds of migration in an electrical
field (electrophoresis). When a gene product
consists of two subunits (dimeric protein), heterozygous
individuals will show three bands. A
polymorphism that does not lead to a change in
electric charge cannot be identified in this manner.
B. Demonstration of polymorphism in gene products
Here, polymorphism is shown to be frequent in
three typical gene products, the enzymes phosphoglucomutase,
malate dehydrogenase, and
acid phosphatase, in different species of Drosophila.
Each of the diagram sections 1, 2, and 3
shows a starch gel electrophoresis of 12 fruit
flies, each gel being specifically stained for the
respective protein. With phosphoglucomutase
(1) different migration speeds are observed in
homozygous individuals as opposed to heterozygous
(2, 4, 10). Malate dehydrogenase is a
dimeric protein, so that heterozygous individuals
(4, 5, 6, 8) show three bands. Acid
phosphatase (3) shows a complex pattern because
four alleles are involved. (Figure after
Ayala and Kieger, 1984).
C. Frequency of polymorphism
In a study of average heterozygosity in Drosophila
willistoni (1), 17.7% of 180 gene loci were
found be heterozygous. The average heterozygosity
is the proportion of heterozygous individuals
in a population with reference to the
number of analyzed loci. This is determined by
summing the proportion of heterozygotes per
total number of individuals per gene locus. The
best insight into the considerable frequency of
polymorphism is obtained from direct analysis
of DNA. Hypervariable regions are found in
many areas of the genome. Here, digestion with
a restriction enzyme produces several different
patterns due to individual differences in the
size of the DNA fragments. In (2), the polymorphism
at one locus near the H chain of the immunoglobulin
J region in 16 individuals is
shown (White et al., 1986). Hypervariable regions
lead to an individual pattern for each person
D. Genetic diversity and evolution
A population of genetically relatively homogeneous
individuals is less likely to be able to
adapt to changing environmental conditions
than is a genetically diverse species. Two populations
of Drosophila serrata kept for 25 generations
in separate closed bottles with limited
availability of space and nourishment were
compared. The population with the greater
genetic diversity adjusted better to the environmental
conditions. (Figure after Ayala &
Ayala, F.J., Kieger, J.A.: Modern Genetics. 2nd ed.
Benjamin/Cummings Publishing Co., Menlo
Park, California, 1984.
Beaudet, A.L., et al.: Genetics, biochemistry, and
molecular basis of variant human phenotypes.
pp. 53–118 In: C.R. Scriver, et al., eds.
The Metabolic and Molecular Bases of Inherited
Disease. 7th ed. McGraw-Hill, New
Bearn, A.: Archibald Garrod and the Individuality
of Man. Clarendon Press, Oxford, 1993.
White, R., et al.: Construction of human genetic
linkage images. I. Progress and perspectives.
Cold Spring Harbor Symp. Quant Biol. 51:29,