UNIT 6 GENETIC POLYMORPHISMS

Contents
6.0 Introduction
6.1 Genetic Polymorphism
6.2 Serological Markers
6.3 Biochemical Markers
6.4 Molecular Markers
6.4.1 Single Nucleotide Polymorphism (SNP)
6.4.2 Restriction Fragment Length Polymorphisms (RFLP)
6.4.3 Variable Number of Tandem Repeats (VNTR)
6.4.4 Insertion Deletion Polymorphisms
6.4.5 Lineage Markers
6.4.5.1 Mitochondrial Markers
6.4.5.2 Y chromosomal Markers

6.5 Biochemical Polymorphisms versus DNA Polymorphisms

6.6 Applications of Genetic Polymorphism
6.7 Significance of Genetic Polymorphisms
6.8 Balanced and Transient Polymorphism
6.8.1 Balanced Polymorphism
6.8.2 Transient Polymorphism
6.9 Models Explaining Maintenance of Genetic Polymorphism
6.9.1 Relationship Between Sickle Cell Anemia and Malaria
6.9.2 X linked Polymorphism
6.10 Summary
6.11 References
6.12 Answers to Check Your Progress

Learning Objectives
After reading the unit, you will be able to:
 Define the concept of genetic polymorphism;

 Explain genetic polymorphism with respect to serological, biochemical

and molecular markers;

 Discuss the use of studying polymorphic markers;

 Understand the concept of balanced and transient polymorphism; and

 Explain models contributing to maintenance of genetic polymorphism.

Contributed by Dr. Ketaki Chandiok, PhD (Anthropology), Delhi

94
6.0 INTRODUCTION Genetic
Polymorphisms
Before we begin with the discussion on genetic polymorphism, it is essential that
we understand what a gene is? A gene can be defined as a segment of the DNA
that specifies the sequence of amino acids in a particular protein. Throughout the
life cycle of a cell, it is the DNA that directs the cellular functions and exists in
an uncoiled granular form. However, during the life cycle of the cell, the normal
activities of the cell might cease and the cell divides. Cell division results in the
production of new cells. At this stage, the DNA is highly coiled and visible under
a microscope as a discrete structure called chromosomes. During the early stage
of cell division, when the chromosomes become visible, they are made up of
two strands or two DNA molecules that are joined together at a constricted area
called the centromere. Chromosomes are present in identical sets of two (or in
pairs). Humans have 46 chromosomes or 23 sets of chromosomes. Of these, 22
pairs are autosomes and other two are sex chromosome that is X and Y. The sex
chromosomes determine the sex that is either male or female. The autosomes
are responsible for all physical characteristics of an individual except primary
sex determination.

Human cells contain around 28000-30000 genes (Deloukas et al., 1998). These
genes code for important and necessary information that determine molecular
traits that are passed on from parents to their offspring. Genes encode various
traits like hair color, eye color, skin color, hair texture, etc. Any change in the
DNA sequence brings about change in the genetic information, which brings
about change in the phenotypic expression and also the associated biological
function. The changes in the DNA sequence is known as a mutation. Physical
anthropologists are concerned in understanding visible human variations as they
are interested not only in identifying the factors that produce visible physical
variation but also the underlying genetic determinants that dictate it. Genetic
variations arise due to the differences in the DNA sequence among populations
from the wild type form. Each and every individual has two sets of genomes,
one maternal and one paternal. Therefore, at each genetic location (locus), the
alleles from the maternal and the paternal side, can either have identical DNA
sequence or slightly differing DNA sequence. The wild type form in a population
refers to individuals with normal phenotype. The wild type form is usually
possessed by the majority of the individuals in the population. In contrast to
this, mutant type refers to individuals with a phenotype that varies from the
normal population. These variations can also be referred to as homozygous if
the alleles on both the chromosomes are identical or heterozygous if they differ
on any one of the chromosomes.

6.1 GENETIC POLYMORPHISM

The term “polymorphism” is a combination of two Greek words “poly” meaning
multiple and “morph” meaning form, can be defined as a mendelian trait, which
exists in a population, in at least two different forms. Ford, 1940 defines genetic
polymorphism refers to the occurrence together in the same habitat of two or
more discontinuous forms or phases of a species in such proportions that the
95
Genetic Structure rarest of them cannot be maintained by recurrent mutations. In simpler words,
of Human genetic polymorphism refers to the occurrence in the same population of two
Populations
or more than two alleles at the same locus in the same population, such that
the frequency of the rarer allele is always greater than one percent and the
rarer allele is maintained in the population, not merely be recurrent mutations
(Cavalli-Sforza and Bodmer, 1971). In the nutshell, polymorphisms can be
defined as the variations in the DNA sequence that are present in the population,
with the frequency of the variation being greater than 1 percent. In other words,
it can be said that mutation frequency is more than 1 percent in a population,
it is a polymorphism. Insertions-deletions polymorphisms, single nucleotide
polymorphisms, restriction site polymorphisms or restricted fragment length
polymorphism etc. are some of the examples of genetic polymorphisms.

Check Your Progress

1) What is Genetic Polymorphism?

Most of the polymorphic traits studied are known to be genetic in nature. The
polymorphic traits are inherited in a Mendelian fashion. In case a population
has more than one version of the same trait, then the population is said to be
polymorphic for that trait, such as blood group type A, type B and type O.
Genetic polymorphisms confer diversity within a population and hence are used
to study population diversity, migration patterns and relationship between and
within various populations and also the potential affinities of populations.

A few genetic markers which show polymorphism are presented below:

6.2 SEROLOGICAL MARKERS

Blood groups are the best examples of serological markers. Blood groups (that
is ABO and Rh) are one of the most important serological markers that play an
important role in blood transfusion and organ transplantation. The ABO blood
group system discovered by Landsteiner is one of the examples of tri-allelic
inheritance. These markers follow Mendelian inheritance. The genetic system
for the ABO blood group is located in chromosome number 9 and has three
major alleles, A, B and O. In this, the A and B allele behaves as co dominant and
O as recessive. The phenotypes A, B, AB and O are present in all populations but
vary in proportions in different parts of the world. The ABO blood group is one
of the most studied genetic polymorphism systems in the Indian subcontinent
with B allele frequencies being highest for most of the populations in the Indian
subcontinent.

The Rh system is one of the most complex polymorphic systems in humans. The
96 antibody was discovered by Levine and Stetson in 1939. Later, it was reported
to be located on chromosome number 1. The red blood cells are designated as Genetic
Rh+ and Rh- depending upon the presence or absence of major D antigen. The Polymorphisms
antigens for the Rh system are defined as products of three loci:C,D and E and
the antigens C,c,D,d,E and e have been studied extensively. For the Rh system,
high frequency of D allele has been reported, with the CDe haplotype being the
most common.

The blood group systems are important for understanding population diversity
and human genetic ethnic ancestry.

6.3 BIOCHEMICAL MARKERS

Individuals in a population are known to differ on the basis of biochemical
markers for example human red cell enzymes like adenylate kinase,
phosphoglucomutase, G6PD and serum proteins like haptoglobin, transferrin,
immunoglobulins etc., hemoglobins and thalassaemia etc.

Glucose 6 phosphate deficiency is one of the most well studied polymorphisms.

The G6PD gene is located on the long arm of the X chromosome (Xq28) region
chromosome. It is a 18 kb long gene consisting of around 13 exons, transcribed
to a 2.269 Kb messenger RNA with 1.545 Kb coding region. The G6PD
deficiency in the male subjects can be detected using the simplest fluorescent
spot test by Beutler and Mitchell, 1968. The method relies on fluorescence of
NADPH, generated by an amount of G6PD enzyme. In Hong Kong, a routine
screening for G6PD deficiency is done for newborns. The commonest variant
of G6PD, the G6PD Canton, has been reported from South China, where it
has been sequenced and was reported to be due to a mutation in the nucleotide
position 1376 of the cDNA, G to T, resulting in a missense mutation at amino
acid position 459, for Arg to Leu (Cavalli-Sforza and Bodmer, 1971).

6.4 MOLECULAR MARKERS (DNA

POLYMORPHISM)
A DNA polymorphism is a sequence difference compared to a reference standard
that is present in at least 1-2% of a population. The genetic polymorphism
occurs in the DNA sequences in numerous ways. There can be different types of
genetic polymorphisms, depending upon the number of nucleotides involved in
the polymorphism and also the reason about how those variations have occurred.

DNA polymorphism can be studied in the following forms:

6.4.1 Single Nucleotide Polymorphism (SNP)

These are the most common type of all the polymorphisms. Human genome,
that is the complete genetic material in a cell consists of about 3 billion base
pairs. SNP occurs in every 300 nucleotides, meaning that there are around 10
million SNPs that are present in the human genome. The nucleotide base pair
substitutions that occur can be between the purines (that is A, G) or pyrimidine
97
Genetic Structure (C, T) are known as transitions. Transitions make up two thirds of all the SNP.
of Human Another type of base pair substitution occurs between a purine and a pyrimidine.
Populations
This is known as a transversion. The single nucleotide polymorphisms occur
either in the coding region of the genes or its non-coding region. The SNP that
occurs within the coding region can be either synonymous or non-synonymous.
The synonymous changes do not affect the amino acid sequence whereas the
non-synonymous changes the sequence of the amino acid. Further, the non-
synonymous SNPs can be either missense or nonsense. Missense mutation
refers to the change in the single base pair that causes substitution of some
different amino acids. In contrast to this, non- sense mutation refers to the
change in the DNA sequence, leading to a premature stop codon or producing a
non-functional, incomplete and truncated protein.

6.4.2 Restriction Fragment Length Polymorphisms (RFLP)

Restriction site polymorphisms (RSPs) are a subset of the SNPs that cause
either a loss or gain of a restriction site. A restriction site can be defined as
a location where a particular restriction enzyme cuts the DNA sequence, at
a particular DNA sequence location, resulting in pieces of DNA. The change
in the nucleotide sequence at a particular site location from the original one,
enables the enzyme to cut the DNA into pieces. This results in creation of a
different length of DNA piece in an individual and another DNA piece in some
another individual. This is restriction site polymorphisms. The RSPs can also
be described as restriction fragment length polymorphism (RFLP).

Expression SNPs refers to the SNPs present in the splicing regions of the
gene that can affect the gene splicing, lead to m RNA degradation, or the non-
coding RNA sequences. They can occur either upstream or downstream of the
gene.

6.4.3 Variable Number of Tandem Repeats (VNTR)

These are arrays of 2 or more base pair core units, located in the non- coding
region of the genome, adjacent to each other. Variable number of tandem repeats
refer to a condition where the number of nucleotides in the core unit is variable
or is not known. On the basis of the size of the core unit, they can be categorized
as either

a) mini-satellites (10-60 bp) is a collection of moderately sized arrays,

usually 10-60 base pairs of tandemly repeated DNA sequences that are
dispersed over considerable portions of the nuclear genome. For example:
GATACCCCAAAG GATACCCCAAAG GATACCCCAAAG is an array
of 12 nucleotide repeats from 3-20 kbp.

b) microsatellites (<10 bp) or short tandem repeats is a small array of tandem

repeats of a simple nucleotide sequence which is usually less than 10 base
pairs. For example, GATA GATA GATA GATA GATA GATA has 4 bases
repeated 6 times. TA TA TA TA TA TA is a dinucleotide repeat and TAT
TAT TAT TAT TAT is a trinucleotide repeat. The STRs were first used in the
98 Persian Gulf War in 1991 for identification of human remains.
6.4.4 Insertion Deletion Polymorphisms Genetic
Polymorphisms
These refer to genetic variations in which a sequence of DNA is either inserted
or deleted from the gene. The frequency of the occurrence of the insertion
deletion polymorphism is only about one tenth of the frequency of the SNPs.
Studies have shown that around 90 percent of the insertion deletions are of
1-10 nucleotides only. Around 9 percent have sequences involving 11 to 100
nucleotides, whereas only 1 percent have sequences greater than 100 nucleotides
(Mullaney et al., 2010). Alu Indels is one of the most widely studied insertion
deletion polymorphism for human evolutionary and diversity studies, because
of their known ancestral state, identification by descent, a wide and common
occurrence and stability.

SNP (https://medium.com/@sanogenetics/snp-of-the-week-58e23927c188)

Restriction Fragment Length Polymorphisms (RFLP) or Restriction site

polymorphisms (RSPs)
(https://www.ncbi.nlm.nih.gov/probe/docs/techrflp/)

Variable Number of Tandem Repeats

(https://www.sciencedirect.com/topics/immunology-and-microbiology/short-
tandem-repeat)

Insertion Deletion (https://www.pathwayz.org/Tree/Plain/

BASE+DELETIONS+%26+INSERTION)
Fig. 6.1 Various forms of Genetic Polymorphism 99
Genetic Structure 6.4.5 Lineage Markers
of Human
Populations 6.4.5.1 Mitochondrial Markers
DNA in humans is not present only in the nuclear regions of the cells, but
also the mitochondria of the human cells and is known as the mitochondrial
DNA (mtDNA) consisting of 16,569 nucleotides. The mtDNA is transmitted
from the mothers only and hence both males and females receive it through
the mothers only. Mitochondrial DNA can be obtained from hair shaft, skeletal
remains etc, which are poor sources of nuclear DNA Mitochondrial markers
present on the mitochondrial haploid genome are used for tracing the maternal
ancestral lineage. This is because of their uni-parental mode of inheritance. The
mitochondrial genome consists of multiple copies of mt DNA.

6.4.5.2 Y Chromosomal Markers

They can be used for tracing the paternal ancestral lineages. The Y chromosome
is transmitted unchanged from one generation to the next. Few changes occur,
but they do not produce any effect as 98% of the DNA is non-coding.

6.5 BIOCHEMICAL POLYMORPHISMS

VERSUS DNA POLYMORPHISMS
The traditionally studied polymorphisms are the serum protein polymorphisms,
blood group polymorphisms and red cell enzymes etc have been studied for
long. These polymorphisms are in the functional region of the genome and
are under the influence of natural selection and therefore, there is restricted
variation in it. In contrast to this, the DNA polymorphisms are found in the
nonfunctional regions of the genome and have much higher levels of variation,
making DNA polymorphisms extremely useful for population genetic studies.
There are numerous polymorphisms that are known at the level of DNA.
Therefore, DNA polymorphism helps in study of haplotype variation, which is
more informative in human population genetic studies.

6.6 APPLICATIONS OF GENETIC

POLYMORPHISM
The applications of genetic polymorphisms in anthropology are numerous. A
few of them are listed below:

1) Understanding the population history and its affinities with other populations.
For understanding the affinities, the DNA sequence of the individuals from
different populations is studied.
2) Understanding and inferring the demographic histories of the populations.
3) Understanding the mutation patterns and its reconstruction.
4) Dating occurrences of the mutations in the populations.
5) Mapping of the disease genes and risk prediction.
100
6) Tracing the trials of the disease and other genes. Genetic
Polymorphisms
7) Identification of genetic matches for organ and marrow donation.
8) Understanding the influence of genetic factors on drug response and
metabolism like explaining the underlying unexpected drug effects,
clarifying the understanding of the molecular mechanisms, evaluating the
clinical relevance etc.
9) Identification of an individual and paternity testing.

6.7 SIGNIFICANCE OF GENETIC

POLYMORPHISM
Genetic polymorphisms are known to affect the protein functions and play an
important role in human health. Genetic polymorphism plays an important
role in the understanding of the biochemical pathways. It is important to note
that the human polymorphisms are present in almost all the racial groups
known, although the frequency may vary between different populations. An
understanding of the gene frequency helps one to know about the evolutionary
past and also helps in the prediction of the biological future.

The polymorphic markers can also be used in personal identification. In addition

to this, the polymorphic markers also help in paternity testing of the children or
fetus, identification of forensic samples in murder cases, rape or assault cases.
The polymorphic markers also find utility in population studies as well. With
technology advancement numerous polymorphic markers have been reported
and the gene frequency data are used for studying the evolution of the human
race. Previously, classical serological and biochemical markers were studied.
The practical utility of these markers was limited due to the limited number of
possible genotypes available at each loci. However, the discovery of the hyper
variable DNA loci, tries to ameliorate this problem. Here, it is important to note
that not the study of one or two loci, but understanding the distribution of a
large number of genetic loci can be used to understand the genetic relationship
among populations. While understanding the genetic relationship between
populations, it is necessary that proper markers are selected and appropriate
statistical tools are used. Recording population variation is necessary as it
helps in understanding the mechanism causing variation and also helps in
understanding the molecular basis of diseases.

6.8 BALANCED AND TRANSIENT

POLYMORPHISM

6.8.1 Balanced Polymorphism

Balanced polymorphism is characterized by the presence of both the alleles for
the gene, rather than having two copies of a single allele alone. Here both the
versions of the alleles are maintained. In nature, balanced polymorphism occurs
101
Genetic Structure when there is a stable frequency of the alleles overtime due to selection. This
of Human type of polymorphism is characterized by heterozygous condition and brings
Populations
about heterozygote advantage. Individuals that carry both the versions of the
alleles are more fit and are able to survive and reproduce, as compared to those
having two copies of the either form. Balanced polymorphism results when
an allele that is harmful in the homozygous state may produce a heterozygote,
the reproductive fitness of which exceeds the homozygote. Hence, balanced
polymorphism is when natural selection favors heterozygote over both the
homozygous recessive and dominant. The superiority of the heterozygous over
the homozygotes is responsible for maintenance of balanced polymorphism in
a population and is referred to as heterozygote superiority or overdominance or
single locus heterosis. E.B. Ford coined the term balanced polymorphism to the
evolutionary process that maintains the heterozygote over a long period.

Balanced polymorphism neither allows elimination of alleles nor its fixation. In

balanced polymorphism, the heterozygote is fitter than the mutant or the wild
type homozygous and is able to survive and hence is selected. Therefore, the
mutation is maintained in an intermediate frequency and it is not fixed. Balanced
polymorphism is an important factor that is known to steadily maintain the
polymorphism in a population for a long period of time and hence is important
in conferring genetic variability to a population. This allows the individuals in a
population to adapt to the rapidly changing environmental conditions.

A few examples of balanced polymorphism are presented below:

Sickle Cell Disease

Sickle cell disease is an example of balanced polymorphism. Sickle cell disease
is caused through a single nucleotide mutation in the beta globin gene. This
causes the production of abnormal hemoglobin characterized by sickle shaped
red blood cells. These sickle shaped red blood cells are fragile and clog the
blood vessels resulting in organ damage, severe anaemia and heart failure. This
autosomal recessive disorder is characterized by joint pain, swollen spleen, and
severe infections.

Malaria is known to be quite common in the tropical regions of Africa. The

heterozygous carriers of sickle cell condition are resistant to malaria (a condition
caused by Plasmodium falciparum parasite; characterized by chills and fever).
Those who are heterozygous for the sickle cell trait, have a mixture of both
the normal erythrocytes as well as the sickle shaped cells. In contrast to these,
the homozygous carriers of the sickle cell gene have a higher frequency of the
sickle cell shaped red blood cells in the population. The work by A.C. Allison in
1954 reported that in spite of the deleterious characteristics of the homozygote,
the sickle cell mutation is maintained in the population as the heterozygote
possesses a selective advantage, which is of being malaria resistant. Therefore,
the heterozygote advantage of the sickle cell red blood cells, provides a protective
effect as the malarial parasite cannot grow in these cells. Therefore, in areas
where malaria is prevalent, those with sickle cell heterozygote condition, tend
to survive and increase in frequency over the normal homozygotes as they are
102 susceptible to malaria.
In this context, sickle cell disease provides a classic example of balanced Genetic
polymorphism, where heterozygotes have a state of co-existence with the Polymorphisms
disadvantageous homozygotes in the population. Here, balanced selection or
polymorphism results through a balance of the selection against the homozygous
sickle cell sufferers and selection against the normal homozygous due to
malaria. Therefore, there is an increased fitness as the heterozygote survives at
a rate much higher than the mutation rate.

G6PD Deficiency
G6PD deficiency is another example of balanced polymorphism, where natural
selection acts in two opposite directions. G6PD deficiency is a sex linked enzyme
deficiency. The deficiency is associated with hemolytic anemia, which is a life
threatening condition. The condition is associated with certain environmental
conditions like inhaling pollen, eating fava beans or certain drugs, or contracting
some infections. Studies from Africa have reported that hemi zygous males
and heterozygous females for the G6PD enzyme deficiency are at a less risk
for having malaria. Since both the heterozygous and hemi zygotes are selected
for, the mutant allele should predominate in the malaria exposed environment.
However, this does not happen. This is because of natural selection. Those with
enzyme deficiency, that is hemizygous males and homozygous females are
selected out of the population due to anaemia. In this context, natural selection
acts in two directions with the hemizygous males selecting for the mutant alleles
as it protects against malarial infection and selecting against due to enzyme
deficiency. This is balanced polymorphism.

Other examples of balanced polymorphism include beta thalassemia,

ovalocytosis, Tay-Sachs Disease, cystic fibrosis, PKU etc.

6.8.2 Transient Polymorphism

Transient polymorphism is when there is a progressive replacement of one
allele by another allele of the gene. The rare allele starts gaining an overall
advantage, thereby spreading in the population. This will reduce the frequency
of the normal allele. Here, one of the alternate forms of the allele is progressively
replaced by another due to inheritance. This happens under the influence of
strong environmental selective pressure, which eliminates one of the alleles
from the gene pool. Transient polymorphism is when there is changing gene
frequency over time. Herein a form is gradually replaced by another one. It can
be thought of as a temporary situation that can be characterized as a by product of
directional selection. In case of transient polymorphism, the mutation gradually
fixes itself due to selection, and there is an elimination of the alternative alleles,
which can lead to an increase in its frequency overtime.

A classic example of transient polymorphism is the phenomenon of industrial

melanism occurring in the moth species of Europe and the United States.
E.B. Ford, a British ecological geneticist, was the first one to demonstrate
the phenomenon of industrial melanism as an effect of natural selection. The
moth Biston betularia, undergoes a mutation at a single locus to produce dark
and melanic form. The mutant allele in this case is dominant and any gamete 103
Genetic Structure containing this mutant allele produces a melanic form. In 1848, the first melanic
of Human form was found in a collection from Manchester. However, by 1895, around
Populations
95% of the collected forms were dark forms, also referred to as carbonaria.

During the 1950s, H.B.D Kettlewell, through a series of 12 observations and

mark recapture, demonstrated that the light and dark forms of the moth species,
was preyed upon differently by the birds. Kettlewell findings reported that the
birds selectively caught and ate more moths of the form that did not match
the background. In the industrialized areas of England, the walls and the tree
trunks on which the moths used to rest were darkened by the pollutants from the
factories. Due to this, the carbonaria possessed a selective advantage. In contrast
to this, in the rural areas, the light form enjoyed a selective advantage. The
carbonaria form produced by recurrent mutations, protected it from predation
by birds. The light form still exists in rare numbers in nature, highlighting that
the selection takes a great amount of time to eliminate the recessive allele.

Fig. 6.2 : Transient Polymorphism (https://ib.bioninja.com.au/higher-level/topic-10-genetics-

and-evolu/103-gene-pools-and-speciati/polymorphisms.h)

Check Your Progress

2) What is Balanced and Transient Polymorphism?

6.9 MODELS EXPLAINING MAINTENANCE OF

GENETIC POLYMORPHISM

6.9.1 Relationship between-sickle Cell Anemia and Malaria

Malaria along with the sickle cell anaemia condition is high in tropical regions
of Africa. The sickle cell disease is less common in Caucasians due to less
occurrence of malaria in the region. Carriers with the heterozygous sickle cell
trait are more resistant to malaria, than the normal homozygotes. It is a well
104 known fact that malaria is quite common in the tropical regions of Africa.
Individuals with the sickle shaped red blood cells have a selective advantage Genetic
as the malarial parasite Plasmodium falciparum cannot grow in these cells. The Polymorphisms
parasite spends the first part of its life cycle in the mosquito Anopheles gambiae
salivary glands. When the infected mosquito bites an individual, the parasite
enters the red blood cells and is transported to the liver. The blood cells burst
releasing the parasite throughout the body. Cultural development along with the
emergence of agriculture lead to an increase of Anopheles mosquitoes owing
to the breeding ground provided due to cultivation of crops. The adaptation to
agricultural mode of subsistence is one of the key determinants explaining the
occurrence of the malarial parasites in the red blood cells of the humans. Those
with sickle cell diseases can change their intracellular environment, so that the
parasite never develops in them. In this context, the normal individuals have
higher mortality and lower fertility rates in malarial environments as compared
to those with sickle cell disease, thereby, contributing more people to the
succeeding generations. Therefore, as the malaria rose, the selective pressures
gives rise to changes in the shape of RBC to sickle cell shape from elliptical.
Regions with settlements of those with a large number of sickle cell carriers
have escaped the devastating malaria incidence. As of today, as well, sickle cell
disease is more prevalent in agricultural societies as compared to hunter and
gatherer societies.

6.9.2 X linked Polymorphism

There are 4 types of genetic polymorphisms that are X linked, these are: colour
blindness, G6PD deficiency, Xg blood group and Xm. Here we will discuss the
first two polymorphisms as the last two are not associated with any selective
effects, so the forces that maintain them cannot be explained fully.

G6PD deficiency is a X linked recessive trait and occurs largely in populations

residing in regions where malaria is prevalent and is associated with resistance to
malaria. G6PD is a sex linked enzyme deficiency and is known to affect around
400 million people worldwide. The deficiency is associated with hemolytic
anaemia, which is a life threatening condition and is also under the influence of
conditions like eating fava beans, inhaling pollen, taking drugs, and catching
certain infections. Studies from Africa have reported that hemizygous males
and heterozygous females for the enzyme deficiency are less likely to develop
malaria, revealing a selective advantage. In areas with malaria attack cells
carrying the normal allele are more prone to rapid destruction by the parasite.
The G6PD enzyme deficiency is responsible for the lower concentration of a
substance called reduced glutathione, which is necessary for the growth of the
malarial parasites.

Colour blindness/ colour vision deficiency is a X-linked recessive trait wherein

the majority of the colour blind people can see colours barring red, green or
blue. Individuals with normal colour vision can distinguish between colours
by the addition of three colours i.e., red, green and blue. The red green colour
blindness can be of the following main types:

105
Genetic Structure 1) Protan (red blind) type with the subtypes of absolute/ strong colour blindness
of Human (protanopia) and partial/ mild (protanomalia).
Populations
2) Deutran (green blind) type with the subtypes of absolute/strong colour
blindness (deuteranopia) and partial/ mild (deuteranomalia).

In most populations there are about three times as many deutan males as protan
males. Studies have shown that there are differences between populations for
the total frequency of colour blindness. The more primitive populations have a
lower frequency, wherein the hunting gathering communities had a prevalence
of 1-2 percent, the industrial society had a prevalence of about 7 percent. The
colour blindness condition was a disadvantage to the primitive people as it
impaired their inability to distinguish between flora and fauna that is essential
for livelihood. The negative selection was more so relaxed in modern societies,
which explains its higher prevalence in such societies.

Check Your Progress

3) Explain the relationship between Sickle Cell anaemia and Malaria

6.10 SUMMARY
Genetic polymorphism, refers to the occurrence of multiple forms of single
allele/gene in an individual of a population, such that the rarest one cannot be
maintained by recurrent mutations and the frequency of neither of which is
less than 1 percent. The polymorphism can be either serological, biochemical
and molecular. The polymorphism that results when the allele is in the process
of replacement is transient. As the favoured allele is fixed in the population it
becomes monomorphic. Balanced polymorphism is the presence of both the
alleles for the gene, rather than having two copies of a single allele alone.

6.11 REFERENCES
Crow, J.F. & Kimura M. (1970). An Introduction to Population Genetics
Theory. New Jersey: Blackburn Press.

Deloukas, P., Schuler, G. D., Gyapay, G., Beasley, E. M., Soderlund, C.,
Rodriguez-Tome, P., & Bentley, D. R. (1998). A physical map of 30,000 human
genes. Science, 282 (5389), 744-746.

Li, C.C. (1976). First Course in Population Genetics. USA: Boxwood Press.

106
Cavalli Sforza, L.L. & Bodmer, W.F. 1971. The Genetics of Human Populations. Genetic
San Francisco. USA: W.H. Freeman, Polymorphisms

Ford, E. B. (1940). Polymorphism and Taxonomy. In The New Systematics, ed.

Huxley, J., pp 493-513. Oxford: Clarendon Press.

Dobzhansky, T. (1951). Genetics and the Origin of Species. New York: Columbia
University Press.

Gardner, E.D, Simmons, M.J & Snustad, D.P. (2003). Principles of Genetics,
8th Edition, New York: John Wiley and Sons.

Simmons, S & Simmons, M.J. (2003). Principles of Genetics, 3rd Edition, New
York: John Wiley and Sons.

6.12 ANSWERS TO CHECK YOUR PROGRESS

1) Ford (1940) defines genetic polymorphism refers to the occurrence together
in the same habitat of two or more discontinuous forms or phases of a
species in such proportions that the rarest of them cannot be maintained
by recurrent mutations. In simpler words, genetic polymorphism refers to
the occurrence in the same population of two or more than two alleles at
the same locus in the same population, such that the frequency of the rarer
allele is always greater than one percent and the rarer allele is maintained
in the population, not merely be recurrent mutations (Cavalli-Sforza and
Bodmer, 1971)

2) Balanced polymorphism is characterized by the presence of both the alleles

for the gene, rather than having two copies of a single allele alone. Here both
the versions of the alleles are maintained. In nature, balanced polymorphism
occurs when there is a stable frequency of the alleles overtime due to
selection. This type of polymorphism is characterized by heterozygous
condition and brings about heterozygote advantage. Individuals that carry
both the versions of the alleles are more fit and are able to survive and
reproduce, as compared to those having two copies of the either form.

Transient polymorphism is when there is a progressive replacement of

one allele by another allele of the gene. The rare allele starts gaining an
overall advantage, thereby spreading in the population. This will reduce the
frequency of the normal allele. Here, one of the alternate forms of the allele
is progressively replaced by another due to inheritance. This happens under
the influence of strong environmental selective pressure, which eliminates
one of the alleles from the gene pool.

3) Malaria is known to be quite common in the tropical regions of Africa.

The heterozygous carriers of sickle cell condition are resistant to malaria
(a condition caused by Plasmodium falciparum parasite; characterized by
chills and fever). Those who are heterozygous for the sickle cell trait, have

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Genetic Structure a mixture of both the normal erythrocytes as well as the sickle shaped cells.
of Human In contrast to these, the homozygous carriers of the sickle cell gene have a
Populations
higher frequency of the sickle cell shaped red blood cells in the population.
The work by A.C. Allison in 1954 reported that in spite of the deleterious
characteristics of the homozygote, the sickle cell mutation is maintained in
the population as the heterozygote possesses a selective advantage that is of
being malaria resistant. Therefore, the heterozygote advantage of the sickle
cell red blood cells, provides a protective effect as the malarial parasite
cannot grow in these cells. Therefore, in areas where malaria is prevalent,
those with sickle cell heterozygote condition, tend to survive and increase in
frequency over the normal homozygotes as they are susceptible to malaria.

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