Variation in human beings as a quality of

life and a genetic

phenomenon

Ass. Nedoshytko Khrystyna

VARIATIONVARIATION

The term variation describes the difference The term variation describes the difference in characteristics shown by organisms in characteristics shown by organisms belonging to the same natural population or belonging to the same natural population or species. It was the amazing diversity of species. It was the amazing diversity of structure within any species that caught the structure within any species that caught the attention of Darwin and Wallace during their attention of Darwin and Wallace during their travels. The regularity with which these travels. The regularity with which these differences in characteristics were inherited differences in characteristics were inherited formed the basis of Mendel's research.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 VARIATIONGENETIC VARIATION

Genetic variation arises in two principal Genetic variation arises in two principal ways:ways:

I. Formation of new combinations I. Formation of new combinations (genotypes) by shuffling of parental genes, (genotypes) by shuffling of parental genes,

and and

II. Modification in chromosomes and II. Modification in chromosomes and genes (DNA) called genes (DNA) called mutationmutation..

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 in structure of the nucleotides).

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 ProblemsAneuploidy

• 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

n - 1

chromosome alignments at metaphase I

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 non-disjunction is a form of trisomy called Down's syndrome (2n = 47).

47,47,XY (21+)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.

4466, XY, t (15q21q), 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 mutationsA 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

UAC is changed to UAU, there is no noticeable effect, because both of these codons code for tyrosine.

Nonsense mutation

If UAC is changed to UAG, however, the result could very well be a drastic one because UAG is a stop codon. If this substitution occurs early in the gene, the resulting protein may be too short and may be unable to function.

Missense mutation

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

NH2

CH

O

CH2

CH2

ONH2

OH

Glutamine

NH 2

CH

CHCH 3

O

CH 3

OH

Valine

Sticky Situation

Low Oxygen

Hemoglobin PolymerizesHemoglobin Polymerizes

Sickling Cells

Polymers of hemoglobindeform 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 MutationThe 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, 5-bromouracil, 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!Thank you for attention!