integrating molecular studies and evolution

Peter Preethlall 1

INTEGRATING MOLECULAR STUDIES AND EVOLUTION

Presented by

Peter PreethlallDCES:TLS-FET, Umlazi District

FEBRUARY 2011

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Outcomes:Educators will understand

an overview of the above contenthow some aspects of the above may be integratedThe concepts of gene mutation and chromosomal aberrationCauses and effects of mutation

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Format of presentation:1. Evolutionary science and

society2. Relationship among: variation,

natural selection and speciation

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BIODIVERSITY, CHANGE & CONTINUITYEvolutionary science and society:1. Conservation / preservation1. Selective breeding2. Health applications:

3.1 Pathogens evolve – drug resistance ?3.2 Identification of pathogens – now and future by phylogenetic analysis3.3 Vaccine development and use3.4 Origins of emerging disease3.5 Population diversity and the evolution of antibiotic resistance 3.6 Discovering new drugs3.7 Predict disease outbreaks and charaterize, trace the origins of and fight diseases3.8 Better understand human physiology, dietary needs, adaptations to health stressors3.9 Identify 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

NATURAL

SELECTION

VARIATION

EVOLUTION

Sources of variation

1. meiosis:

* crossing-over

*random arrangement of chromosomes

2. chance fertilization

3. Mutations

-adaptation to the environment

-’survival of the fittest’

-micro-evolution – speciation

- macro-evolution

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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 anotherVariation is the raw material for evolutionary changeThis is controlled by genesArises by recombination; gene mutation and chromosomal mutationOnly gene mutations result in new allelesChromosomal mutations and recombination – contribute greatly to the production of variant genotypes and phenotypes

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Sources of phenotypic variation: current viewsPhenotypic 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 prophaserandom 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 processE.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

Newcastle Hospital

035 20910

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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

NormalmRNA

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 mutationConsider the ffg. analogy:THE DOG BIT THE CAT

THE DOG BIT THE CAR

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GENE MUTATIONS

mRNAProtein

NormalmRNA

Protein

Frameshift

mutationProteins 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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GENE MUTATIONS

Bending impairsits function

Part ofprotein isremoved

New sectionof amino acidsintroduced

LDLR gene causing FH – different mutations can cause the same disease

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GENE MUTATIONS

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Chromosomal AberrationsThe 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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There are four common type of structural aberrations:

1. Deletion or Deficiency 2. Insertion /Duplication or Repeat3. Inversion, and 4. Translocation.

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Deletion

Occurs when part of a chromosome is left out

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Structural Chromosomal AberrationsDeletion 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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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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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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INVERSIONS

Occur when part of one chromosome breaks out and is inserted backwards

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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-disjunctionMitotic non-disjunction: The failure of : The failure of separation of homologous chromosomes separation of homologous chromosomes during mitosis is called mitotic non-during mitosis is called mitotic non-disjunction. disjunction.

It occurs after fertilization.It occurs after fertilization.

May happen during first or second May happen during first or second cleavage. cleavage.

Here, one blastomere will receive 45 Here, one blastomere will receive 45 chromosomes, while other will receive 47. chromosomes, while other will receive 47.

Meiotic non-disjunctionMeiotic non-disjunction: The failure of : The failure of separation of homologous chromosomes separation of homologous chromosomes during meiosis is called meiotic non-during meiosis is called meiotic non-disjunctiondisjunction

Occurs during gametogensisOccurs during gametogensis

Here, one type contain 22 chromosome, Here, one type contain 22 chromosome, while other will be 24.while other will be 24.

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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 chromosomeUsed 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 SyndromeThe 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 syndrome250,000 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 handsSome 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 birthsAt 45 years 1 in 40 births.

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NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION

Natural selection brings about adaptation to the environmentBut it has no particular goal Because the environment is constantly changingTherefore perfect adaptation is not a probable outcome of natural selectionNatural 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…

PRECONDITIONS1. 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. An increasing proportion of individuals in succeeding generations have the adaptive characteristics

B. The result of natural selection is a population adapted to its local environment

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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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Organisms struggle to exist- Death & famine inevitable since population size

increases faster than supply of food- i.e. availability of resources – low – always competitionOrganisms 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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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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MICROEVOLUTION BY NATURAL SELECTIONe.g. Peppered moths of Manchester

Example : Peppered moths of ManchesterIn the early 19th century, both dark-coloured and light-coloured moths lived in ManchesterThe light-coloured moths were in greater numbersWhen 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 light-coloured moths and ate themThe 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 environmentThe dark-coloured moths reproduced and produced more dark-coloured mothsToday 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

integrating molecular studies and evolution

Documents

macro evolution

recombination of chromosomes

meiosis gametes

recombination gene mutation

mutations adaptation

chance processif

chance fertilization3

chromosomal aberrationcauses