INTEGRATING MOLECULAR STUDIES AND EVOLUTION

1. Presented by Peter Preethlall DCES:TLS-FET, Umlazi District FEBRUARY 2011 INTEGRATING MOLECULAR STUDIES AND EVOLUTION Peter Preethlall

2. 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 Peter Preethlall

3. INTEGRATING MOLECULAR STUDIES AND EVOLUTION Format of presentation: 1. Evolutionary science and society 2. Relationship among: variation, natural selection and speciation Peter Preethlall

4. BIODIVERSITY, CHANGE & CONTINUITY Evolutionary science and society: 1. Conservation / preservation • Selective breeding • 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 3.5 Population diversity and the evolution of antibiotic resistance 3.6 Discovering new drugs 3.7 Predict disease outbreaks and charaterize, trace the origins of and fight diseases 3.8 Better understand human physiology, dietary needs, adaptations to health stressors 3.9 Identify organisms and metabolic processes for bioremediation “Evolutionary biology is medicines missing basic science” Peter Preethlall

5. Explanation of Evolution in terms of Current Knowledge VARIATION Sources of variation 1. meiosis: * crossing-over *random arrangement of chromosomes 2. chance fertilization 3. Mutations NATURAL SELECTION -adaptation to the environment -’survival of the fittest’ EVOLUTION -micro-evolution – speciation - macro-evolution Peter Preethlall

6. 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 Peter Preethlall

7. 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 Peter Preethlall

8. 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 Peter Preethlall

9. Gametes produced by meiosis are different because of : Crossing-over during first prophase random arrangement of chromosomes during first metaphase Sources of genetic variation : Meiosis Peter Preethlall

10. 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 Peter Preethlall

11. 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. Peter Preethlall

12. 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 3 Peter Preethlall

13. 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 Peter Preethlall

14. 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! Peter Preethlall

15. GENE MUTATIONS mRNA Normal Protein mRNA Point mutation 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. Peter Preethlall

16. 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 Peter Preethlall

17. GENE MUTATIONS mRNA Normal Protein mRNA Frameshift 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. Peter Preethlall

18. GENE MUTATIONS • Frameshift mutations - A mutation in which a single base is added or deleted from DNA Peter Preethlall

19. GENE MUTATIONS Peter Preethlall

20. Sickle cell anaemia – missense mutation Peter Preethlall

21. 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 Peter Preethlall

22. GENE MUTATIONS Peter Preethlall

23. 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. Peter Preethlall

24. 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 Peter Preethlall

25. 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 Peter Preethlall

26. 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. Peter Preethlall

27. Structural Chromosomal Aberrations Deletion Occurs when part of a chromosome is left out Peter Preethlall

28. 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. Peter Preethlall

29. 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. Peter Preethlall

30. 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 Peter Preethlall

31. Structural Chromosomal Aberrations INVERSIONS Occur when part of one chromosome breaks out and is inserted backwards Peter Preethlall

32. Structural Chromosomal Aberrations TRANSLOCATIONS Occur when part of one chromosome breaks off and is added to a different chromosome Peter Preethlall

33. 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 ormeiosis or embryogenesis. Peter Preethlall

34. Peter Preethlall

35. 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 during gametogensis • Here, one type contain 22 chromosome, while other will be 24. Peter Preethlall

36. 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. Peter Preethlall

37. 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. Peter Preethlall

38. 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. Peter Preethlall

39. 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 isestimated at $ 1 billion per year. Peter Preethlall

40. 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. Peter Preethlall

41. 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) Peter Preethlall

42. 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 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 NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION – Contd… Peter Preethlall

43. 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. NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION – Contd… Peter Preethlall

44. 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 Peter Preethlall

45. NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION – COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING Peter Preethlall

46. NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION – COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING E.g. of a useful mutation:A lamb born withshort, bent legs that prevented it from jumping fences. Used in breeding to establish short-legged sheep. Peter Preethlall

47. NATURAL SELECTION PROVIDES A MECHANISM FOR EVOLUTION – COMPARE WITH ARTIFICIAL SELECTION / SELECTIVE BREEDING Peter Preethlall

48. 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 MICROEVOLUTION BY NATURAL SELECTIONe.g. Peppered moths of Manchester Peter Preethlall

49. Birds easily spotted the light-coloured 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 MICROEVOLUTION BY NATURAL SELECTION e.g. Peppered moths of Manchester Peter Preethlall

50. MICROEVOLUTION BY NATURAL SELECTION e.g. Peppered moths of Manchester Peter Preethlall