Today Genetic variability & mutations: source of variation in organisms

1. Today Genetic variability & mutations: source of variation in organisms

2. The nature of science Methodological Naturalism [We can only test natural causes. There may be a diety.] (This is what Science does) v. Philosophical Naturalism [All phenomena have natural causes. There is no diety.] (This is a philosophical view point. Science doesn’t require this viewpoint, but it isn’t incompatible with science.)

4. Where does variation come from?How is it inherited? PBS, NOVA

5. Darwin didn’t know. (Mendel did) PBS, NOVA Where does variation come from?How is it inherited?

6. What Darwin Didn’t Know • Heredity: Darwin wasn’t aware of Mendeliangenetics, • so he didn’t understand how heritability worked • (2) Genetics: mutation had not been discovered, so Darwin couldn’t explain where variation came from

7. What Darwin Didn’t Know • Heredity: Darwin wasn’t aware of Mendeliangenetics, • so he didn’t understand how heritability worked • (2) Genetics: mutation had not been discovered, so Darwin couldn’t explain where variation came from • In many cases: Variation in the PHENOTYPE (appearance) • means Variation in the Genotype (DNA)

8. What Darwin Didn’t Know • Heredity: Darwin wasn’t aware of Mendeliangenetics, • so he didn’t understand how heritability worked • (2) Genetics: mutation had not been discovered, so Darwin couldn’t explain where variation came from 1930s-1950s Scientific Revolution: “The Modern Synthesis” Darwinian Natural Selection PLUS Heredity, Genetics, and Paleontology

9. The Modern Synthesis: Natural Selection, +Heredity & Genetics • 4 postulates of Natural Selection: • (1) Individuals within a species are variable because mutation creates new alleles (allele = version of a gene) and sexual reproduction creates new allele combinations in every generation. • (2) Some of this variation, as particular alleles, is passed to their offspring (in other words, traits are heritable) • (3) More offspring are produced each generation than can survive (this is the “struggle for life”) • (4) Individuals with the most favorable variations survive and produce the most offspring.

10. Misconception:Evolution is random and adaptations occur by chance.

11. Misconception:Evolution is random and adaptations occur by chance. Evolutionary Theory says: 1) Mutations are random (with respect to where they occur a and when).

12. Misconception:Evolution is random and adaptations occur by chance. • Evolutionary Theory says: • Mutations are random (with respect to where they occur and when). • 2) Adaptations are the outcome of non-random Natural Selection. Mutations create variation.

13. Misconception:Evolution is random and adaptations occur by chance. • Evolutionary Theory says: • Mutations are random (with respect to where they occur and when). • 2) Adaptations are the outcome of non-random Natural Selection. Mutations create variation. Variation is the “raw material of evolution.”

14. DNA Mutations: creator of genetic variability • Mutations in DNA are mistakes. • These mistakes in genes create variation

15. DNA Mutations: creator of genetic variability • Mutations in DNA are mistakes. • These mistakes in genes create variation • Alleles are versions of the same gene that differ in their DNA base sequence (ex. A instead of G) • This variation from mutation is what Natural Selection acts on…

16. DNA Mutations: creator of genetic variability • Mutations in DNA are mistakes. • These mistakes in genes create variation • Alleles are versions of the same gene that differ in their DNA base sequence • The variation from mutation is what Natural Selection acts on… DNA mistakes + selection created the diversity of life (!)

17. Mutation and Genetic Variation complimentary base pairs Changes in the DNA sequence create new alleles in every generation • Purine • Pyrimidine • T & C • A & G

18. Pyrimidines: TUC • Thymine, Uracil, Cytosine • TUC • Biscuits

19. Review: DNA  Protein Types of DNA Mutations • Transcription • Translation

20. mRNA codons & Amino Acids

21. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence • Cause: DNA polymerase error: • (a) during DNA replication • (b) during repair of damaged DNA • damage by: chemical mutagens, free radicals, radiation (nuclear, sun, etc.) • Consider the consequences of these mutations happening during meiosis and mitosis… • Meiosis mutations = germ line (gametes) • Mitosis mutations = somatic tissues (individual)

22. Types of DNA Mutations • DNA polymerase error: • (a) during DNA replication • (b) during repair of damaged DNA • chemical mutagens • - can intercalate (stick into) the DNA helix, • distorting the shape and causing excision • (cutting out) of bases • (2) free radicals • - oxygen atoms or OH molecules • that have single electrons (electron-hungry) • - damage DNA bases • (3) radiation • - UV from sunlight can cause thymine to bond with itself, whichneeds to be excised (= cut out)

23. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- -C-A-G-

24. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- • Transition • Purine to Purine (A,G) • Pyrimidine to Pyrimidine (T,C) -C-A-G- -C-A-A- • Transversion • Purine to Pyrimidine • Pyrimidine to Purine -C-A-C-

26. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- • Transition (More Common) • Purine to Purine (A,G) • Pyrimidine to Pyrimidine (T,C) -C-A-G- -C-A-A- • Transversion (Less Common) • Purine to Pyrimidine • Pyrimidine to Purine -C-A-C-

27. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- • Transition (More Common) • Purine to Purine (A,G) • Pyrimidine to Pyrimidine (T,C) -C-A-G- • Transversion (Lesss Common) Why? • BecauseTransversions stick two • non-complimentary bases next to one another, causing an irregularity in the DNA helix that is more likely to get noticed and fixed by repair enzymes -C-A-A- -C-A-C-

28. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- G-U-U: Valine • Synonymous mutation: makes the same amino acid -C-A-G- G-U-C: Valine

29. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- G-U-U: Valine • Synonymous mutation: makes the same amino acid -C-A-G- G-U-C: Valine • also called silent substitutions (“silent” to phenotype) • common when the change is at the 3rd position • no good or bad change to organism (neutral) • Note: this is still considered a new allele, since the DNA sequence changed (although the protein is unchanged)

30. Types of DNA Mutations • point mutation: a single-base substitution • in the DNA sequence -C-A-A- G-U-U: Valine • Synonymous mutation: makes the same amino acid -C-A-G- G-U-C: Valine -C-A-A- G-U-U :Valine • Non-Synonymous: makes a different amino acid -T-A-A- :Isoleucine A-U-U

31. Types of DNA Mutations • Non-Synonymous mutation • (can be a transition or transversion) • these mutations alter the protein product of the gene • often a change in the 1st or 2nd position of a codon • influence the phenotype of the organism • most non-syn mutations hurt the organism -C-A-A- G-U-U :Valine • Non-Synonymous: makes a different amino acid -T-A-A- :Isoleucine A-U-U

32. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • 1) A frameshift mutation (by insertion or deletion)

33. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • 1) A frameshift mutation (by insertion or deletion) DNA sequence Protein sequence (normal) ACA-ATG-GTA-CGA Cys-Tyr-His-Ala (insertion) ACA-GAT-GGT-ACG Cys-Leu-Pro-Val (deletion) ACA-TGG-TAC-GA Cys-Tyr-Met-Leu

34. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • 1) A frameshift mutation (by insertion or deletion) Hypothetical Example: a 2-letter reading frame WE-GO-TO-CS-LA IW-EG-OT-OC-SL-A (insertion of I) EG-OT-OC-SL-A (deletion of W)

35. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • A frameshift mutation (by insertion or deletion) • Mutation to a Stop Codon Insertion of T: ACA-ATT-GTA-CGA mRNA: UAA: STOP

36. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • A frameshift mutation (by insertion or deletion) • Mutation to a Stop Codon • Inactivation by a Transposable Element (transposon) DNA sequence Protein sequence ACA-ATG-GTA-CGA Cys-Tyr-His-Ala ACA-AGG-GGG-CTA-ATG Cys-Ser-Pro-Asp-Tyr “transposon”

37. Types of DNA Mutations: loss of function • loss of function mutation: the amino acid changes • causing the protein to be non-functional • A frameshift mutation (by insertion or deletion) • Mutation to a Stop Codon • Inactivation by a Transposable Element • Transposons (= transposable elements, or “jumping • genes”) inactivate the gene they disrupt. • They may “jump back out” at a later date, restoring • the correct coding sequence

38. Location of DNA Mutations: germ v. soma • Germ cell mutations: occur in eggs and sperm (or • megaspore and pollen in plants) • - These mutations create genetic changes in the next • generation • - Occur during meiosis • Somatic cell mutations: occur in body tissues • These mutations create changes in the mutated individual • Occur during mitosis

39. Types of DNA Mutations In groups Consider the consequences of non-synonymous point mutations and other mutations happening during meiosis and mitosis…

40. Recall that point mutations can take place:a) during DNA replication (meiosis or mitosis) b) during DNA repairThe known causes of these mostly harmful mutations are: (1) chemical mutagens- stick into the DNA helix, distorting the shape and causing cutting out of bases(2)free radicals- oxygen atoms or OH molecules that have single electrons (electron-hungry), which damage DNA bases(3)radiation - UV radiation from sunlight can cause thymine dimers, which need to be cut out

41. Mutation rates vary… (1) among different species (2) between the sexes (3) among individuals (4) among genes (5) Between germ and soma - can vary between individuals, depending on their alleles for: (a) DNA polymerase (some less accurate than others) (b) DNA repair enzymes (some less efficient than others) - often the first genes to become mutated in cancer cells are genes involved in DNA repair

42. DNA Mutations • If most non-syn mutations hurt the organism, where do most beneficial mutations come from? • How are new, functional mutations created?

43. So, how are NEW functional genes created? Gene duplication 1: because of Transposon Mistakes during meiosis can result in unequal crossing over, when a daughter chromosome inherits duplicated regions of a chromosome duplicated “B” gene A B C A B C A B B C crossing over between two transposons can create extra copies of a gene, which may then gain new functions by mutation

44. So, how are NEW functional genes created? Gene duplication 2: because of chromosome rearrangement (inversion) • 2 double-stranded breaks occur in a chromosome, the part in between the breaks may flip and get re-inserted • This results in an inversion, where the gene order is reversed between the break points relative to the normal chromosome reversal of gene order

45. So, how are NEW functional genes created? Gene duplication2: because of chromosome rearrangement (inversion) A B C D E F G a b c f e d g (1) regions will not align during synapsis, when homologs pair (2) crossing over would cause loss of part of the chromosome -so- (3) alleles f, e and d are now linked, and will be transmitted to offspring as one big “supergene”

46. So, how are NEW functional genes created? Gene duplication3: The viral enzyme reverse transcriptase can create gene copies from mRNA transcripts, which then get inserted back onto a chromosome A B C inserts anywhere on any chromosome reverse transcriptase mRNA transcript for the A gene DNA copy of the A gene

47. So, how are NEW functional genes created? Gene duplication3: The viral enzyme reverse transcriptase can create gene copies from mRNA transcripts, which then get inserted back onto a chromosome A B C A A B C = inserts anywhere on any chromosome reverse transcriptase mRNA transcript for the A gene DNA copy of the A gene

48. So, how are NEW functional genes created? Gene duplication4: Duplicate the whole genome! In plants, the production of diploid gametes during meiosis can result in tetraploid offspring: offspring with 4 copies of each chromosome Tetraploid plants cannot produce viable offspring with normal 2N plants, but can breed successfully with other tetraploid individuals One gene has to be functional, the other three are, “free to mutate”

49. Questions?

50. “Induced v. Spontaneous mutation” controversy First confirmation that mutation precedes adaptation came from Luria & Delbruck’s 1943 experiment, called the Fluctuation Test Hypotheses 1: Induced mutation: each E. coli cell has a small chance of surviving a virus, but survivors get “acquired immunity” that can be passed to their offspring - exposure to virus induces resistance (= adaptation) Note: bacteria HAVE TO HAVE a certain mutation to survive exposure to the virus Also, a bacterial colony represents the many descendents of an ancestor