Mutations

1. Mutations

2. Mutations

3. Mutations =Abrupt changes in the genetic material occurring typically during cell division.

4. SOMATIC MUTATIONS Why are these irrelevant to evolution?

5. Types of Mutation • Structural changes in Chromosomes a. Loss or duplication of whole genes deletionsduplications b. Changes in gene arrangement

6. Loss or duplication of whole chunks of DNA e.g. Matthew State of Univ. of California, San Francisco, has discovered variations in chromosome 7. An extra copy of a particular segment (~ 25 genes) greatly increases the risk of autism, which leads to social isolation. But if this section is lost, it results in Williams syndrome, which leads to intense sociability.

7. b.Changes in gene arrangement (1) Translocation—large pieces of chromosome moved to another place in the genome. (2) Transposons—”jumping genes”—small pieces of DNA shifting within the genome. (3) Inversions—Chunks of chromosome flipping over. 2.Numerical changes in chromosomes • Aneuploidy = addition of one or more chromosomes e.g. Extra sex chromosomes (xxy, xxyy, xxxy, etc.)

8. b.Changes in gene arrangement (1) Translocation—large pieces of chromosome moved to another place in the genome. (2) Transposons—”jumping genes”—small pieces of DNA shifting within the genome. (3) Inversions—Chunks of chromosome flipping over. 2.Numerical changes in chromosomes a) Aneuploidy = addition of one or more chromosomes (e.g. Down Syndrome) e.g. Extra sex chromosomes (xxy, xxyy, xxxy, etc.)

9. Down Syndrome Extra chromosome # 21

10. But its not all due to Mom Sperm parent cells divide every 15 days. This continuous division and copying of DNA leads to errors & the rate of error increases significantly with age. A 20 year old man will have an average of 25 new point mutations in his sperm. A 40 year old man will have 65. A 40 year old woman will have 15

12. Men have a much higher rate of mutation than women Data from 150 people in Denmark with complete genome analysis— Nature Aug. 3, 2017

13. b. Polyploidy = multiple copies of the entire genome Characteristic of several plant species e.g. Banana can be 2n = 22; 4n = 44 5n = 55

14. 3. Gene (point) mutations= Nucleotide changesa.SUBSTITIONS DNA CAT TTA GGA GGA AAA Substitution Mutations DNA CAT TTG GGA GGA GAA

15. WHAT HAPPENS? DNA CAT TTA GGA GGA AAA mRNA GUA AAU CCU CCU UUU Pr (aa)VAL ASP PRO PRO PHE BEFORE

16. WHAT HAPPENS? DNA CAT TTA GGA GGA AAA mRNA GUA AAU CCU CCU UUU Pr (aa)VAL ASP PRO PRO PHE BEFORE Substitutions DNA CAT TTG GGA GGA GAA RNA(m) GUA AAC CCU CCU CUU Pr (aa) VAL ASP PRO PRO LEU AFTER Remains the same Changed

17. Gene (point) mutationsb.ADDITIONS DNA CAT TTA GGA GGA AAA Addition Mutation DNA CAT TTA TGG AGG AAA A FRAME SHIFT Thymine added

18. Gene (point) mutations c.SUBTRACTIONS (deletions DNA CAT TTA GGA GGA AAA Subtraction DNA CAT TAG GAG GAA AA FRAME SHIFT

19. 4. Protein chain length modifiers (start and stop codons) Leads to short or extra long non-functional proteins

20. Protein chain length modifiers e.g. Premature stop in the protein sequence DNACAT ATA GGA GGA GAA DNACAT ATT GGA GGA GAA Stop! Produces a short nonfunctional protein

21. e.g. Run-on protein DNACAT ATT GGA GGA GAA DNACAT CTT GGA GGA GAA This substitution produces a longer protein since the CTT now codes for a glutamic acid residue instead of stopping transcription

22. Mutations in Developmental Genes e.g. Heterochronic mutations = alter the rates of growth of some organs relative to others in the organism. Many of the differences between species seem to be due to regulatory genes.

23. e.g. Neoteny sex organs development faster than the somatic cells, producing a sexually precocious organism. Axolotyl

24. Homeotic genes = regulate clusters of genes controlling development Homeotic Gene 5’ a b c d e f 3’ Homeotic mutation Drosophilasp. have at least 8 homeotic genes: e.g. mutation in “antennapedia gene” leads to formation of leg not antennae e.g. Mutation in “bithorax gene leads to two thoraxes and additional wings

25. Homeotic Mutations

26. Causes of mutations • Ionizing radiation (e.g. x-rays) • Chemical mutagens (e.g. nicotine) • Spontaneous mutations during DNA replication. Copy mistakes • CRISPR—Gene Editing Note: Some mutations can be repaired.

27. Mutation rates Rates/million Achondroplastic Dwarfism 40 to 120 Total color Blindness 30 Hemophilia B 20 to 40 Hemophilia A 5 to 10 Most genes1 On average 5% of humans in each generation carry a least one new mutation

28. Gene editing. A whippet dog with myostatin gene edited out with double the muscle mass

29. Effects of mutations • Harmful: They disrupt the normal function of an allele They knock out its function making it recessive Most mutations recessive Not expressed except as aa • Lethal Minor  Major Effects

30. Effects of mutations • No effect = Neutral mutation • Silent mutation – mutation for equivalent codon or equivalent group of amino acids • Mutated gene expressed but the same fitness within the environment blue or brown eyes Each baby has ~130 new mutations. Most are neutral 3. Beneficial = increases the fitness of an organism

31. Mutations and Evolution • Mutations determine survival and reproduction Fitness positive fitness = Fitness negative fitness = Fitness neutral fitness = No change in fitness 2. Most mutations have negative fitness. 3.Mutations are random i.e. not directed by environment

32. To measure the rate of evolution We Need A Clock

33. Molecular Clocks • If mutation is fairly constant, the # of nucleotide differences between species indicates the time that the species have been separated.

34. Primate Evolution-Molecular Clock

35. Calibrating the Clock But you need to know the average rate of mutation

36. Conclusion? • Data strongly support the hypothesis of evolution • All organisms share a common ancestor! • We can draw family trees even if we don’t have a fossil record.