Mutations, Mitosis, Meiosis, & Genetics

1. Mutations, Mitosis, Meiosis, & Genetics HOW are they related??

2. Mutation • A change in the nucleotide sequence of DNA. • May involve a single nucleotide or may involve many nucleotides • WHAT is the effect of a mutation? It may change the PROTEIN the gene encodes!

3. Mutations, cont • Can changing only 1 nucleotide really matter? • YES!! • Mutations may be harmful, beneficial, or unnoticeable to the organism

4. Types of Mutations: 1. Base substitutions: replacement of one nucleotide with another in the DNA of a gene; • Effect depends on whether there is an amino acid change that alters the function of the protein

5. Base Substitution (or Point Mutation), cont. • Change the underlined A to a C Corr: ATA GAT TAC ACG tyr leu met try Mut: ATA GAT TAC CCG tyr leu met gly • As above, RESULT MAY be a Coding Change in 1 amino acid of the protein.

6. 0 Base Substitution, cont. Normal hemoglobin DNA Mutant hemoglobin DNA mRNA mRNA Sickle-cell hemoglobin Normal hemoglobin Glu Val

7. Do Base Substitutions ALWAYS result in a coding change? • NO- change of 1 nucleotide in DNA does NOT always change the amino acid or protein • Ex: CAA CAC Both code for “valine” (VAL) What position of codon is changed? This is a Silent Mutation (NO coding change occurs!)

8. Mutations, cont. 2. Deletions or insertions: Adding or removing a nucleotide(s) in the coding sequence • Alters the “reading frame” of the mRNA, so that nucleotides are grouped into different codons “downstream” of change – a FRAMESHIFT! • Usually results in significant changes in amino acid sequence downstream of mutation; results in a nonfunctional polypeptide!

9. What do we mean by “Reading Frame” & Frameshift?? • Compare the sentences of 3 letter words: • THE CAT ATE THE HOT DOG • What happens if we lose the C? • THE ATA TET HEH OTD OG • Does that make sense??? NO!! It is a Frameshift!!

10. Frame Shift • When the “reading frame” of the gene changes, codons are changed and amino acids are different AFTER the deletion/ insertion. • Radically changes structure & sequence of the protein

11. Deletion (& Frameshift) • 1 or more nucleotides removed from DNA coding sequence; • Ex: DNA TAC GGA TCT AGG ACT • mRNA AUG CCU AGA UCC UGA met pro arg ser stop (start) • Delete the first G; how does this change the amino acids? Does it change 1 or many AA?

12. Deletion & frameshift, cont. • Does it change 1 or many AA? DNA: TAC *GAT *CTA *GGA *CT mRNA AUG *CUA *GAU *CCU *GA Met *leu *asp *pro (Original: Met-Pro-Arg-Ser-stop) * Changed codons AND amino acids!

13. Insertion (& Frameshift) • 1 or more bases are added (inserted!) to the DNA coding sequence; • Add G after the first codon below: GGC ACG TAT CTA TCG GGC GAC GTA TCT ATC G • As in case of deletions, USUALLY results in a reading frame shift. • When does an insertion OR deletion change ONLY 1 amino acid?

14. Normal gene 0 mRNA Protein Lys Met Phe Ala Gly Base substitution Lys Met Phe Ala Ser Base deletion Missing Lys Met Leu His Ala

15. Another possible result: Early Stop mutation • Can happen as a result of a nucleotide change, deletion, or insertion • An early stop codon occurs in the transcript, so the protein is shorter than normal.

16. What causes mutations? • Random changes during DNA replication • Mutagens-environmental factors that cause mutations • Carcinogens-environmental factors that cause mutations that lead to cancer

17. Can you reduce your risk? • YES!!! • Screening for early detection • Avoid tobacco products • Healthy, balanced diet • Wear sunscreen • Get regular exercise

18. Are all mutations BAD? • NO!! • One KEY reason mutations are good: introduce change into the genome! This is necessary for evolution to occur!!

19. Changes in Chromosomes • NUMBER! • During meiosis, Chromosomes fail to separate • Results in too many or too few chromosomes in gamete • Fusion with a normal gamete results in an abnormal number of chromosomes (Monosomy- 1 copy, Trisomy-3 copies) • Is USUALLY lethal to the embryo

20. Chromosomal Mutations • Changes in the structure of one or more chromosomes • Can we see chromosomal mutations? • Yes, if it is a major change- see in karyotype • How can they change?

21. Chromosomal mutations • Chromosomal Deletion • Chromosomal Duplication • Chromosomal Translocation • Chromosomal Inversion • Change in Number

23. Chromosomal duplication: Segment of a chromosome is repeated

24. Translocation – part of chromosome breaks off and becomes part of another chromosome

25. Inversion – part of chromosome breaks off, flips, & reattaches

26. How does it occur?

27. What causes mutations? • Random changes during DNA replication • Mutagens-environmental factors that cause mutations • Carcinogens-environmental factors that cause mutations that lead to cancer

28. What is the life of a Cell? • It’s called the Cell Cycle! • Majority of the cell cycle is spent in “interphase” (G1, S, G2); • S phase is when the DNA replicates • IF necessary, the cell will divide to form daughter cells at the end of the cycle • During Interphase, the cell performs its various functions within organism

29. Cell Division • Why do cells NEED to divide? • Is there only 1 type of division? • NO- there are 2 types of cell division for different purposes!

30. How did we ALL begin? • As ONE cell- the fertilized egg (zygote)!! • How did we become a baby? • Cell division!! • What does that mean? Mitosis!

31. Mitosis • The process where one cell divides into 2 identical cells • This is how 1 cell became millions of cells in an adult! • It is also HOW we grow & repair our bodies. • What has to happen BEFORE mitosis can occur?

32. Answer: DNA replication! • All 46 chromosomes (in humans) have to be copied so both DAUGHTER cells get the same 46 chromosomes that were in the parent cell.

33. Parent cell Chromosomes are copied and double in number (sister chromatids are attached at by the centromere Chromosomes now split 2 daughter cells identical to original

34. Animation of mitosis: • http://www.cellsalive.com/mitosis.htm

35. So, we’ve got 46 chromosomes. • How many different PAIRS of chromosomes do we have? • 23 pairs of chromosomes • How are Males & Females GENETICALLY different?? • Females have 2 X chromosomes • Males have 1 X and 1 Y chromosome- presence of Y makes you a male!!

36. CHROMOSOME NUMBER • Diploid: A pair (2 copies) of each different chromosome; most body cells are diploid; • diploid = 2n (where n is the number of different chromosomes) • The number of chromosomes in egg and sperm cells (gametes) is haploid which is “n”, or 1 copy of each different chromosome What are diploid and haploid for us?

37. Answer: • Diploid= 46chromosomes =2 copies of 23 different chromosomes (1-22 + XX or XY) • Haploid = 1 copy of 23 different chromosomes (1-22 + X or Y)

38. Where does each chromosome of the pair come from? (Ex. You’ve got 2 copies of chr 1- where did each copy come from?) • One chromosome comes from MOM, and one chromosome comes from Dad

39. So, who determines the sex of a baby???? • DAD- He is the ONLY parent that can contribute the Y chromosome that makes the fetus male.

40. How do the gametes (sex cells) end up with only 23 chromosomes? THINK MEIOSIS!! • WHY do they need to be haploid (only 1 copy of each chromosome or 23 total chromosomes)?

41. MEIOSIS IT’S ALL ABOUT SEXUAL REPRODUCTION…

42. MEIOSIS • A type of cell division where the number of chromosomes is reduced by half • ONLY occurs in gonads (ovaries or testes) during formation of gametes (egg or sperm) • Human body cells have 46chromosomes; human sperm and egg cells each have 23 chromosomes

43. Gametes are haploid for SEXUAL REPRODUCTION! • When egg and sperm combine during fertilization, each brings half the total number of chromosomes for that species • Half + half = whole • In humans, 23 chromosomes (from Dad) + 23 chromosomes (from Mom) = 46 chromosomes (child) !!!

44. FERTILIZATION egg + sperm = zygote 23 + 23 = 46 n n 2n Haploid + haploid = diploid

45. Summary of Meiosis • Type of cell division used to form the gametes (egg & sperm) where chromosome number is reduced to haploid (n). • Chromosomes assort RANDOMLY so each gamete is unique! This increases biodiversity of species. • It involves 2 cell divisions, NOT 1 like in mitosis. • Results are 4 haploid daughter cells!

46. Animation of Meiosis • http://www.cellsalive.com/meiosis.htm

47. MORE ABOUT CHROMOSOMES • In humans, there are 22 different “regular” chromosomes (numbered 1 to 22 by size & shape) and 2 different sex chromosomes • The sex chromosomes are X and Y • Which sex chromosomes are in a girl? XX • Which are in a boy? XY

48. Karyotype • A photograph of all of an organisms chromosomes. • Scientists freeze cells at the metaphase of mitosis. At this stage, chromosomes are easy to isolate and stain.

49. What to look for in a Karyotype? • When analyzing a human karyotype, scientists first look for these main features: 1. Are there 46 chromosomes? 2. Are there 2 identical pairs of each autosome and 2 sex chromosomes? 3. Are there any rearrangements between chromosomes or large deletions?

50. Why perform a karyotype? • Verify chromosome number (some genetic diseases are caused by MORE copies of a chrom.) • Confirm chromosome shape, structure and size.