Transcript mutations - Curriculum Development

INTEGRATING MOLECULAR STUDIES
AND EVOLUTION
Presented by
Peter Preethlall
DCES:TLS-FET,
Umlazi District
FEBRUARY 2011
Peter Preethlall
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INTEGRATING MOLECULAR STUDIES
AND EVOLUTION
Outcomes:
Educators will understand
an overview of the above content
how some aspects of the above may
be integrated
The concepts of gene mutation and
chromosomal aberration
Causes and effects of mutation
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INTEGRATING MOLECULAR STUDIES
AND EVOLUTION
Format of presentation:
1. Evolutionary science and society
2. Relationship among: variation,
natural selection and speciation
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BIODIVERSITY, CHANGE & CONTINUITY
Evolutionary science and society:
1. Conservation / preservation
1.
Selective breeding
2.
Health applications:
3.1 Pathogens evolve – drug resistance ?
3.2 Identification of pathogens – now and future by phylogenetic analysis
3.3 Vaccine development and use
3.4 Origins of emerging disease
3.5Population diversity and the evolution of antibiotic resistance
3.6 Discovering new drugs
3.7Predict disease outbreaks and charaterize, trace the origins of and
fight diseases
3.8 Better understand human physiology, dietary needs, adaptations to
health stressors
3.9Identify organisms and metabolic processes for bioremediation
“Evolutionary biology is medicines missing basic science”
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Explanation of Evolution in terms of Current
Knowledge
VARIATION
Sources of variation
1. meiosis:
* crossing-over
*random arrangement of
chromosomes
NATURAL
SELECTION
2. chance fertilization
-adaptation to
the environment
-’survival of the
fittest’
EVOLUTION
3. Mutations
-micro-evolution –
speciation
- macro-evolution
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Explanation of Evolution in terms of
Current Knowledge
Current theories accept Darwin’s ideas on natural
selection but :
Explain the sources of variation
Distinguish between micro-evolution, speciation
and macro- evolution
Provide possible explanations for mass extinctions
Provide “evidence” for evolution
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WHAT CAUSES VARIATION?
Members of a population vary from one another
Variation is the raw material for evolutionary change
This is controlled by genes
Arises by recombination; gene mutation and
chromosomal mutation
Only gene mutations result in new alleles
Chromosomal mutations and recombination –
contribute greatly to the production of variant genotypes
and phenotypes
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Explanation of Evolution in terms of Current
Knowledge
Sources of phenotypic variation: current views
Phenotypic variations are due to variations in the
genetic constitution (genotype)
The genotype might be different because ..
 Meiosis brings about the recombination of
chromosomes and alleles which results in the
formation of unlike gametes.
* crossing-over between non-sister chromatids
* independent assortment of chromosomes
 Chance/Random fertilisation of egg cells by
sperm cells
 Mutations
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Sources of genetic
variation :
Meiosis
Gametes produced by
meiosis are different because
of :
Crossing-over during first
prophase
random arrangement of
chromosomes during first
metaphase
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Sources of genetic variation:
Chance / Random Fertilisation
– Usually more than one egg cell and sperm
cell is produced
– Fertilisation is a chance process
– If there were just 4 egg cells and 4
sperm cells there are 16 possible
genotypes of the offspring
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Sources of genetic variation:
Chance / Random Fertilisation
The entire genotype and NOT individual alleles is
subjected to the natural selection process
E.g. In a population of snails stripes & brown colour
combined might make them less visible in a woodland
habitat,
If stripes are controlled by one allele and brown colour
by another allele, it is a combination of the two alleles
that will be selected for.
Recombination may at some time bring the two alleles
together so that the combined phenotype can be
subjected to natural selection.
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MUTATIONS
•
•
•
Have you ever copied a phone no.
incorrectly?
What are some of the possible
consequences of this?
Mistakes in the DNA code can produce
similar results
Sometimes – no effect on organisms,
but often causes serious consequences
for individual organisms
Peter Preethlall
Newcastle Hospital
035 20910
3
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MUTATION – A CHANGE IN DNA
A change or mistake in the DNA sequence is called a mutation.
Generally occurs during the cell processes that copy genetic material
and pass it from one generation to next
These processes are usually accurate to ensure genetic continuity in
both new cells and offspring
However, sometimes mistakes can occur
Changes in the DNA base sequence is referred to as gene mutations
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Sources of genetic variation:
Mutations
Mutations are sudden, random changes in the genetic code
of an organism
There could be gene mutations and chromosomal mutations
Gene mutations
Gene mutations provide new alleles, and are therefore the
ultimate source of variation. A gene mutation is an alteration
in the DNA nucleotide sequence of an allele.
Mutation rates are very small in nucleic DNA(1 in 100 000 to
1 in 10 000 000) but rather high in mt DNA.
If the human genome has 50 000 genes, it means that half
the egg cells and half the sperm cells will have mutations
Which means that all of us have at least one mutant gene!
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GENE MUTATIONS
Normal
mRNA
Protein
Point mutation
mRNA
Protein
The base G was replaced with A. Resulted in insertion of serine
instead of glycine into the growing aa chain – creating another
protein. Sometimes these errors do not interfere with protein
function, but often the effect is disastrous.
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GENE MUTATIONS
Point Mutation
-Is a change in a single base pair in
DNA
Effects of point mutation
Consider the ffg. analogy:
THE DOG BIT THE CAT
THE DOG BIT THE CAR
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GENE MUTATIONS
Normal
mRNA
Protein
Frameshift mRNA
mutation
Protein
Proteins produced through fm seldom function properly. Why?
Adding or deleting one base of DNA molecule will change every
amino acid in the protein after the addition or deletion.
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GENE MUTATIONS
Frameshift mutations
- A mutation in which a single base is added or
deleted from DNA
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GENE MUTATIONS
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Sickle cell anaemia – missense mutation
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LDLR gene causing FH – different mutations can cause the same disease
GENE MUTATIONS
Part of
protein is
removed
New section
of amino acids
introduced
Bending impairs
its function
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GENE MUTATIONS
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Chromosomal Aberrations
The somatic (2n) and gametic (n) chromosome numbers of a
species ordinarily remain constant.
This is due to the extremely precise mitotic and meiotic cell
division.
Somatic cells of a diploid species contain two copies of each
chromosome, which are called homologous chromosome.
Their gametes, therefore contain only one copy of each
chromosome, that is they contain one chromosome complement
or genome.
Each chromosome of a genome contains a definite numbers and
kinds of genes, which are arranged in a definite sequence.
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Chromosomal Aberrations
Sometime due to mutation or spontaneous
(without any known causal factors), variation in
chromosomal number or structure do arise in
nature. - Chromosomal aberrations.
Chromosomal aberration may be grouped into
two broad classes:
1. Structural and 2. Numerical
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Structural Chromosomal Aberrations
- These are changes at the level of
chromosomes
- May occur in a variety of ways
* parts of chromosomes are broken off
and lost during mitosis or meiosis
* Chromosomes may break and rejoin
incorrectly
* Sometimes the parts join backwards
or join
to the wrong chromosomes
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Structural Chromosomal Aberrations
There are four common type of structural
aberrations:
1. Deletion or Deficiency
2. Insertion /Duplication or Repeat
3. Inversion, and
4. Translocation.
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Structural Chromosomal Aberrations
Deletion
Occurs when part of a chromosome is left out
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Structural Chromosomal Aberrations
Deletion generally produce striking genetic and
physiological effects.
When homozygous, most deletions are lethal, because
most genes are necessary for life and a homozygous
deletion would have zero copies of some genes.
When heterozygous, the genes on the normal
homologue are hemizygous: there is only 1 copy of
those genes.
Crossing over is absent in deleted region of a
chromosome since this region is present in only one
copy in deletion heterozygotes.
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Structural Chromosomal Aberrations
Deletion in Humans:
Chromosome deletions are usually lethal even
as heterozygotes, resulting in zygotic loss,
stillbirths, or infant death.
Sometimes, infants with small chromosome
deficiencies however, survive long enough to
permit the abnormal phenotype they express.
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Structural Chromosomal Aberrations
INSERTION / DUPLICATION
Occurs when part of a chromatid breaks off and
attaches to its sister chromatid. The result is a
duplication of genes on the same chromosome
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Structural Chromosomal Aberrations
INVERSIONS
Occur when part of one chromosome breaks out and
is inserted backwards
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Structural Chromosomal Aberrations
TRANSLOCATIONS
Occur when part of one chromosome breaks off and
is added to a different chromosome
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Non-Disjunction
Generally during gametogenesis the homologous
chromosomes of each pair separate out (disjunction)
and are equally distributed in the daughter cells.
But sometime there is an unequal distribution of
chromosomes in the daughter cells.
The failure of separation of homologous chromosome is
called non-disjunction.
This can occur either during mitosis or meiosis or
embryogenesis.
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Mitotic
non-disjunction: The failure of separation of
homologous chromosomes during mitosis is called mitotic
non-disjunction.
It
occurs after fertilization.
May
happen during first or second cleavage.
Here,
one blastomere will receive 45 chromosomes, while
other will receive 47.
Meiotic
non-disjunction: The failure of separation of
homologous chromosomes during meiosis is called meiotic
non-disjunction
Occurs
Here,
be 24.
during gametogensis
one type contain 22
chromosome,
while
other
will
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Variation in chromosome number
Organism with one complete set of chromosomes is said
to be euploid (applies to haploid and diploid organisms).
Aneuploidy - variation in the number of individual
chromosomes (but not the total number of sets of
chromosomes).
The discovery of aneuploidy dates back to 1916 when
Bridges discovered XO male and XXY female
Drosophila, which had 7 and 9 chromosomes
respectively, instead of normal 8.
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• Nullisomy - loss of one
homologous chromosome
pair. (e.g., Oat )
• Monosomy – loss of a
single chromosome
(Maize).
• Trisomy - one extra
chromosome. (Datura)
• Tetrasomy - one extra
chromosome pair.
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Uses of Aneuploidy
They have been used to determine the phenotypic effect of
loss or gain of different chromosome
Used to produce chromosome substitution lines. Such
lines yield information on the effects of different
chromosomes of a variety in the same genetic background.
They are also used to produce alien addition and alien
substitution lines. These are useful in gene transfer from
one species to another.
Aneuploidy permits the location of a gene as well as of a
linkage group onto a specific chromosome.
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Trisomy in Humans
Down Syndrome
The best known and most common chromosome related syndrome.
Formerly known as “Mongolism”
1866, when a physician named John Langdon Down published an
essay in England in which he described a set of children with
common features who were distinct from other children with mental
retardation he referred to as “Mongoloids.”
One child in every 800-1000 births has Down syndrome
250,000 in US has Down syndrome.
The cost and maintaining Down syndrome case in US is estimated
at $ 1 billion per year.
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Trisomy in Humans
Patients having Down syndrome will Short in stature (four feet tall)
and had an epicanthal fold, broad short skulls, wild nostrils, large
tongue, stubby hands
Some babies may have short necks, small hands, and short fingers.
They are characterized as low in mentality.
Down syndrome results if the extra chromosome is number 21.
The risk for mothers less than 25 years of age to have the trisomy is
about 1 in 1500 births.
At 40 years of age, 1 in 100 births
At 45 years 1 in 40 births.
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NATURAL SELECTION PROVIDES A
MECHANISM FOR EVOLUTION
Natural selection brings about adaptation to the
environment
But it has no particular goal
Because the environment is constantly changing
Therefore perfect adaptation is not a probable
outcome of natural selection
Natural selection is a process in which
preconditions 1 – 3 may result in certain
consequences (A & B) – (table on next slide)
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NATURAL SELECTION PROVIDES A
MECHANISM FOR EVOLUTION – Contd…
PRECONDITIONS
1. The members of a
population have heritable
variations
2. In a population, many more
individuals are produced
in each generation than
can survive and reproduce
3. Some individuals have
adaptative
characteristicsthat
enable them to survive
and reproduce better
than do other individuals
CONSEQUENCES
A.
B.
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An increasing proportion
of individuals in
succeeding generations
have the adaptive
characteristics
The result of natural
selection is a population
adapted to its local
environment
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NATURAL SELECTION PROVIDES A
MECHANISM FOR EVOLUTION – Contd…
Organisms have variations
Members of a population
vary in their functional,
physical and behavioural
characteristcs
Variations are essential to
the natural selection
process
Occurrence of variation is
completely random
The variations that make
adaptation to the
environment possible are
passed on from gen. to gen.
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NATURAL SELECTION PROVIDES A
MECHANISM FOR EVOLUTION – Contd…
Organisms struggle to exist
- Death & famine inevitable since population size increases
faster than supply of food
- i.e. availability of resources – low – always competition
Organisms differ in fitness
- fitness is the ability of an organism to survive and reproduce
in its local environment
- The fittest will survive and obtain a disproportionate amount
of resources, and convert this into viable offspring
Organisms become adapted
- adjust to be more suited to its environment
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NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION –
COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING
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NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION –
COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING
E.g. of a useful mutation:
A lamb born with short, bent legs that prevented it from jumping fences.
Used in breeding to establish short-legged sheep.
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NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION –
COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING
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MICROEVOLUTION BY NATURAL SELECTION
e.g. Peppered moths of Manchester
Example : Peppered moths of
Manchester
In the early 19th century,
both dark-coloured and
light-coloured moths lived
in Manchester
The light-coloured moths
were in greater numbers
When Manchester became
industrialised black smoke
from the factories
collected as soot on the
tree trunks
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MICROEVOLUTION BY NATURAL SELECTION
e.g. Peppered moths of Manchester
Birds easily spotted the lightcoloured moths and ate them
The dark-coloured moths were
not easy to see and survived in
greater numbers
i.e. nature selected them
because they were better
adapted to the environment
The dark-coloured moths
reproduced and produced
more dark-coloured moths
Today most of the moths of
this species in Manchester are
dark-coloured
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MICROEVOLUTION BY NATURAL SELECTION
e.g. Peppered moths of Manchester
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GENETIC DRIFT
In large populations where random mating occur
and mutation does not take place, the genetic
constitution of the population does not change.
This is known as the Hardy - Weinberg principle
In small populations which have become isolated
from the larger group, there may be rapid change
in the gene frequency of the different alleles.
This is known as genetic drift
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Consequences of micro-evolution
Both natural selection and genetic drift
results in populations where the frequency
of particular genes is higher/lower than
that in the population as a whole
These populations may therefore look
different, behave differently and have
different physiologies (metabolism)
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SPECIATION
Species: a group of organisms that have a large number of
similar characteristics and are able to interbreed to
produce fertile offspring
Population : organisms of the same species occupying the same
habitat at the same time
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SPECIATION
Individuals of a population showing a great deal of variation may
become separated by a geographic barrier
The 2 populations no longer mix
The 2 populations each reproduce, undergo natural selection
(become adapted to their environments) and become
genetically different
These genetic differences may lead to reproductive isolating
barriers, which keep them as distinct species
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TYPES OF SPECIATION
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