Transcript 06.Variation in human beings as a quality of life and a genetic

Variation in
human beings
as a quality of
life and a
genetic
phenomenon
Ass. Nedoshytko Khrystyna
VARIATION
The term variation describes the difference
in characteristics shown by organisms
belonging to the same natural population or
species. It was the amazing diversity of
structure within any species that caught the
attention of Darwin and Wallace during their
travels. The regularity with which these
differences in characteristics were inherited
formed the basis of Mendel's research.
Why does one organism look
different to another ?
• Do the members of
this family have any
similar features ?
• Are the members
different in any ways?
• What reasons can you
think of to explain
these differences ?
Inherited Differences in Humans.
• Genes control the
characteristics that
develop.
• 1/2 the instructions
come from the father
and 1/2 come from
the mother.
• The new individual is
genetically unique
So why are Identical twins not
identical ?
• Twins have identical
genes in their
bodies…….
• Yet they do not have
identical
characteristics.
Why aren’t fruits from the same
plant identical ?
What about this wheat grown in the
same field from the same parent plants?
A study of differences in any large population
shows that two forms of variation:
phenotypic variation and genetic variation.
Phenotypic variation: continuous; discontinuous
• The physical and biochemical characteristics of
an organism make up the phenotype
• The genotype determines the potential of an
organism, environmental factors determines to
what extent it will occur.
• Continuous variation - differences are grade into
each other Ex. human height and weight.
• Discontinuous variation - differences are
discrete usually qualitative. Example dwarf or
tall.
There are certain characteristics within a
population, which exhibit a limited form of
variation. Variation in this case produces
individuals showing clear-cut differences with
no intermediates between them, such as blood
groups in humans.
Characteristics showing discontinuous variation
are usually controlled by one or two major
genes which may have two or more allelic
forms and their phenotypic expression is
relatively unaffected by environmental
conditions.
CONTINUOUS VARIATION
• Gradual or not so clear-cut variation
• The classes are artificial and have been decided upon
by us to make it easier to draw a graph.
• May be caused by genes or environment or both.
• Examples :- weight, leaf length, height, skin colour.
Many characteristics in a population show a complete
gradation from one extreme to the other without any break.
This is illustrated most clearly by characteristics such as
mass, linear dimension, shape and color of organs and
organisms. The frequency distribution for a characteristic
exhibiting continuous variation is a normal distribution
curve.
Most of the organisms in the population fall
in the middle of the range with
approximately equal numbers showing the
two extreme forms of the characteristic.
Characteristics exhibiting continuous
variation are produced by the combined
effects of many genes (polygenes) and
environmental factors. Individually each of
these genes has little effect on the
phenotype but their combined effect is
significant.
ENVIRONMENTAL INFLUENCES
The ultimate factor determining a
phenotypic characteristic is the genotype.
At the moment of fertilization the
genotype of the organism is determined,
but the subsequent degree of expression
allowed to this genetic potential is
influenced greatly by the action of
environmental factors during the
development of the organism.
GENETIC VARIATION
Genetic variation arises in two principal
ways:
I. Formation of new combinations
(genotypes) by shuffling of parental genes,
and
II. Modification in chromosomes and
genes (DNA) called mutation.
I. New Combinations genotypes
arise in 3 ways:
(a) Independent assortment of
chromosomes during gamete
formation;
(b) Reciprocal recombination of linked
genes in chromosomes by crossing
over in the prophase of meiosis I;
and
(c) Random fertilization.
II. MUTATION
Hugo De Vries introduced the term
«mutation» in 1901.
Scientific study of mutation was started by
Thomas Hunt Morgan in 1910 with his
work on Drosophila melanogaster.
The first mutation he reported was a
white-eyed male fly in a population of
normal red-eyed males.
A mutation is a change in the amount or the
structure of the DNA of an organism.
This produces a change in the genotype, which
may be inherited by cells derived by mitosis
or meiosis from the mutant cell.
A mutation may result in the change in
appearance of a characteristic in a
population.
Mutations occurring in gamete cells are
inherited, whereas those occurring in
somatic cells can only be inherited by
daughter cells produced by mitosis. We are
known as somatic mutations.
There are 3 main types of mutations:
1.Chromosomal mutations (changes in
number of chromosomes).
2.Chromosomal aberrations (changes in
structure of chromosomes).
3.Gene (point) mutations (changes
structure of the nucleotides).
in
1. Chromosomal Mutations
Chromosomal mutations may be the
result of changes in the number or
structure of chromosomes. Certain
forms of chromosomal mutation may
affect several genes and have a more
profound effect on the phenotype
than gene mutations.
Changes in the number of
chromosomes are usually the result
of errors occurring during meiosis but
they can also occur during mitosis.
а) These changes may involve the loss
or gain of single chromosomes, a
condition called aneuploidy;
b) or the increase in entire haploid sets
of chromosomes, a condition called
polyploidy.
Chromosome Number Problems
Aneuploidy
• Individuals have one
extra or less chromosome
• (2n + 1 or 2n - 1)
• Major cause of human
reproductive failure
• Most human miscarriages
are aneuploids
Polyploidy
• Individuals have three or
more of each type of
chromosome (3n, 4n)
• Common in flowering
plants
• Lethal for humans
– 99% die before birth
– Newborns die soon
after birth
Nondisjunction
n+1
n+1
n-1
chromosome
alignments at
metaphase I
n-1
nondisjunction
at anaphase I
alignments at
metaphase II
anaphase II
a) Aneuploidy
In this condition half the daughter cells produced
have an extra chromosome, (2n + 1) and so
on, whilst the other half have a chromosome
missing, (2n - 1) and so on.
Aneuploidy can arise from the failure of a pair, or
pairs, of homologous chromosomes to
separate during anaphase I of meiosis.
One of the commonest forms of chromosomal
mutation in humans resulting from nondisjunction is a form of trisomy called Down's
syndrome (2n = 47).
47,XY (21+)
b) Euploidy (Polyploidy)
Gamete and somatic cells containing
multiples of the haploid number of
chromosomes are called polyploids, and
the prefixes tri-, tetra- and so on indicate
the extent of polyploidy,
for example: 3n is triploid,
4n is tetraploid, 5n is pentaploid and so on.
Polyploids is much more common in plants
than in animals.
A modified form of polyploidy can occur in
animals and give rise to cells and tissues,
which are polyploid. This process is called
endomitosis and involves chromosome
replication without cell division.
The giant chromosomes in the salivary
glands of Drosophila and
tetraploid cells in the human liver are
produced by endomitosis.
2. Chromosomal Mutations or
Aberrations
These mutations affect large portions of
the chromosomes and are observable
under a microscope. Crossing over
during prophase I of meiosis involves
the reciprocal transfer of genetic
material between homologous
chromosomes.
Morphological Modifications in
chromosomes
They are of two types:
a) intrachromosomal;
b) interchromosomal;
a) Intrachromosomal modifications.
These changes affect a single
chromosome.
They occur in two ways: - deletion
- inversion.
In both cases, the process involves
breakage and reunion of segments
of chromosomes.
- Deletion
A segment of a
chromosome
separates and is
lost. The affected
chromosome loses
certain genes, and
becomes shorter
than normal.
- Inversion
Occurs when a region of
a chromosome breaks
off and rotates
through 180° before
rejoining the
chromosome.
No change in genotype
occurs as a result of
inversion but
phenotypic changes
may be seen.
b) Interchromosomal modifications.
These changes affect two chromosomes
simultaneously.
They also occur in two ways:
- translocation;
- duplication.
- Translocation.
A segment of
chromosome breaks off
and joins a
nonhomologous
chromosome. Both the
affected chromosomes
get modified.
The donor suffers deletion
and becomes shorter
than normal.
The recipient has an extra
set of genes and
becomes longer than
normal.
Translocation may be
reciprocal.
In some cases of Down's
syndrome, where the diploid
number is normal, the effects
are produced by the
translocation of an extra G21
chromosome onto a larger
chromosome, usually D15.
46, XY, t (15q21q)
- Duplication.
A fragment of a
chromosome joins a
homologous
chromosome.
In some cases a region of
a chromosome
becomes duplicated so
that an additional set of
genes exists for the
region of duplication.
3. Gene mutations
A gene mutation or point mutation is the result
of a change in the nucleotide sequence of the
DNA molecule in a particular region of the
chromosome.
Gene mutations occurring during gamete
formation are transmitted to all the cells of the
offspring and may be significant for the future
of the species.
Somatic gene mutations which arise in the
organism are inherited only by those cells
derived from the mutant cells by mitosis.
Point Mutations
Silent mutation
Nonsense mutation Missense mutation
UAC is changed If UAC is changed to
UAG, however, the
to UAU, there is
result could very well
no noticeable
be a drastic one
effect, because
because UAG is a
both of these
stop codon. If this
codons code for
substitution
occurs
tyrosine.
early in the gene, the
resulting protein may
be too short and may
be unable to function.
Finally, if UAC is
changed to CAC,
then histidine is
incorporated into the
protein instead of
tyrosine.
• A change in one amino acid may not have
an effect if the change occurs in a
noncritical area or if the 2 amino acids
have the same chemical properties. In this
instance, however, the polarities of tyrosine
and histidine differ; therefore, this
substitution most likely will have a
deleterious effect on the functioning of the
protein. Recall that the occurrence of valine
instead of glutamate in the beta (B) chain
of hemoglobin results in a sickle-cell
disease.
Hemoglobin and Sickle Cell Anemia
• Single base mutation in DNA
– A to T transversion
• Single amino acid change in the
protein
– Glutamine to Valine
– Polar charged R group to non-polar R group
H 2N
H 2C
O
H 3C H CH 3
C
CH 2
C
H 2N H
O
C
H 2N H
O
OH
OH
Glutamine
Valine
Sticky Situation
Low Oxygen
Hemoglobin Polymerizes
Sickling Cells
Polymers of hemoglobin
deform red blood cells
Normal
Sickle
Sickle Cell Anemia
• Recessive trait
• Symptoms– Chronic hemolytic anemia
– Severe pain
– Rapid septicemia (infection)
– Asplenia (no spleen left)
Implications of Mutation
The effects of chromosome and gene mutations are very
variable. In many cases the mutations are lethal and
prevent development of the organism.
Some forms of chromosomal mutation may bring certain
gene sequences together, and that combined effect
may produce a «beneficial» characteristic.
Another significance of bringing certain genes closer
together is that they are less likely to be separated by
crossing over and this is an advantage with beneficial
genes.
Origin of Mutations.
Mutations may arise spontaneously due to certain
intracellular factors or be induced by
environmental factors. The latter are called
mutagens or mutagenic agents.
1. Spontaneous Mutations.
These occur at random and their frequency is
rather low. They are thought to arise generally
by errors in the process of replication. Many
cell products such as formaldehyde, peroxides
act as mutagens.
2. Induced Mutations.
The mutagens that induce mutation may be physical or
chemical. The physical mutagens include
radiation and temperature.
(a) Radiations. High-energy radiations such as X-rays,
gamma rays, alpha and beta rays, cosmic rays,
ultraviolet light, etc.. have been found to be
mutagenic in almost all organisms. They produce
mutations by disrupting the chemical structure of
DNA.
(b) Temperature. It is reported that rise in temperature
increases the rate of mutation. Temperature probably
affects the thermal stability of DNA and the rate of
reaction of other substances with DNA.
(с) Chemicals. A variety of chemicals act as
mutagens. These include nitrous acid,
formaldehyde, peroxides, mustard gas, 5bromouracil, etc. Colchicine induces polyploidy
by inhibiting the formation of spindle in cell
division. This doubles the number of
chromosomes as the cell fails to divide.
Thank you for attention!