Genetics, Meiosis, and the Molecular Basis of Heredity

1. Genetics, Meiosis, and the Molecular Basis of Heredity

2. Theories on Inheritance • It was clear for millennia that offspring resembled their parents, but how this came about was unclear. • Do males and females harbor homunculi? • Do the components of sperm and egg mix like paint? • What role do gametes and chromosomes play?

3. Theories on Inheritance • Genetics = the science of heredity • This section will focus on the molecular mechanisms of genetics

4. Genetics, Meiosis, and the Molecular Basis of Heredity • Topics • Sexual reproduction (advantages, disadvantages, meiosis) • Mendelian inheritance • Experimental genetics

5. Simple Inheritance • Bacteria and some other organisms reproduce simply by making exact copies of themselves • This is asexual reproduction

6. Sexual Reproduction • Sexual reproduction involves the mixing of genomes from two individuals to produce offspring that are genetically distinct from either parent and from other offspring • Disadvantages – • very costly to produce specialized cells • interaction with other organisms is dangerous • mixing genes can produce unexpected results • Advantages • One word – variation • The introduction of variation allows for better survival in a changing environment and for the rapid spread or reduction of advantageous and deleterious genes

7. Sexual Reproduction • Sexual reproduction occurs in diploid organisms • Diploid organisms have two complete sets of chromosomes, one from each parent • Diploid organisms therefore carry two copies of most genes • Diploid organisms use haploid cells to reproduce • Haploid cells contain only one copy of each chromosome set

8. Sexual Reproduction • The basics of sexual reproduction • The germ cells (gametes) are haploid • Gametes are generated through meiosis • There are typically two types in animals • A large, immobile egg • Small, mobile sperm • During sexual reproduction, the gametes fuse to produce a diploid zygote

10. Sexual Reproduction:Mitosis review • Diploid cells reproduce through mitosis • Mitosis was covered in Bio 115 • This NOT how gametes are made

11. Sexual Reproduction:Mitosis review • Diploid cells reproduce through mitosis • Homologous chromosomes are duplicated • During mitosis, the duplicated chromosomes are doled out to daughter cells • This example shows a cell with one pair of homologous chromosomes

12. Sexual Reproduction:Meiosis (producing gametes) • In mitosis, a diploid cell produces twodiploid daughter cells • In meiosis, a diploid cell gives rise to fourhaploid cells

13. Sexual Reproduction:Meiosis (producing gametes) • Major differences between mitosis and meiosis • Mitosis – once cell division • Meiosis – two cell divisions • Mitosis – replicated chromosomes line up ‘single file’ during metaphase • Meiosis – replicated homologs line up in pairs during metaphase I and ‘single file’ in metaphase II

14. Sexual Reproduction:Meiosis (producing gametes)

16. Sexual Reproduction:Meiosis (producing gametes) • Variation is introduced to the offspring by combining the chromosomes of both parents into a single cell • A second level of variation is introduced via recombination during meiosis (prophase I) • Recombination is an exchange of material between homologous chromosomes via a process called ‘crossing over’ • Thus, the gametes you produce will be novel combinations of the chromosomes you received from your parents

17. Sexual Reproduction:Recombination

18. Sexual Reproduction:Recombination

19. Sexual Reproduction:Recombination • The end result of meiosis is a pool of gametes in which the genetic information of the parent has been extensively rearranged • Merely by combining different sets of paternal and maternal chromosomes, there are 223 (8,400,000) distinct gametes possible • By introducing recombination you increase that number exponentially

20. Sexual Reproduction:Creating variation

21. Sexual Reproduction:Mistakes during meiosis • A cell must keep track of 92 chromosomes (23 x 4) during meiosis and sometimes errors occur • Nondisjunction – failure of chromosomes to separate properly • Results in gametes with more or fewer than the standard number

22. Sexual Reproduction:Nondisjunction • Zygotes resulting from aneuploid (abnormal chromosome number) gametes typically don’t survive but sometimes do • Down syndrome (trisomy 21) • Edward’s syndrome (trisomy 18) • Patau’s syndrome (trisomy 13)

23. Sexual Reproduction:Fertilization • Fertilization is the union of two gametes to produce a diploid zygote • ~200 of the 3 million sperm in a human male ejaculate reach the egg • To ensure only one sperm fertilizes the egg, a chemical cascade ‘hardens’ the egg once one has fused with it

24. Mendelian Inheritance • As a result of the processed described for sexual reproduction, the genomes of diploid organisms are a mixture of discrete segments of their parents’ genomes • Some traits are inherited in a simple fashion through individual genes. • Other traits are polygenic • Others are simple and/or polygenic and influenced by the environment

25. Mendelian Inheritance • Simple Mendelian inheritance • Attached earlobes • PTC (phenylthiocarbamide) tasting • ‘uncombable hair’ • Complex (polygenic) inheritance • Eye color • Height • Studying inheritance in humans is difficult for ethical reasons but more easily done in other organisms

26. Mendelian Inheritance • Named for Gregor Mendel • 1822-1884 • Studied discrete (+/-, white/black) traits in pea plants

27. Mendelian Inheritance • Mendel began with true-breeding plants • True-breeding - when mated with themselves or others of the same type, produce the same offspring • Cross-pollinated these true breeding varieties • Crossed the offspring (F1’s) with each other or back to the parents • Kept very detailed numerical records of the offspring of each cross

28. Mendelian Inheritance • A classic experiment • What did it tell Mendel? • That pod color was inherited as a discrete trait, inheritance was not ‘blended’ for this trait • That one trait was ‘dominant’ over the other • yellow + green ≠ yellow-green • yellow + green = yellow

29. Mendelian Inheritance • By continuing the experiment, more can be learned • The trait that was ‘lost’ in the first generation (F1) was regained by the second (F2) • yellow + yellow = yellow and green • The cause of the trait was not destroyed, but was harbored unseen in the parent • There was a definite mathematical pattern to the occurrence of the traits (3:1)

30. Mendelian Inheritance • Mendel concluded: • Heredity was caused by discrete ‘factors’ (genes) • These ‘factors’ remain separate instead of blending • The ‘factors’ came in different ‘flavors’ (alleles) • Each offspring must inherit one gene from each parent (2 total) • The phenotype (appearance) of the plants was determined by the genotype (actual combination of alleles)

31. Mendelian Inheritance • Genotype vs. phenotype

32. Mendelian Inheritance • The true-breeders only had one type of allele (homozygous) • Each parent passes on one of the alleles they have to the offspring • The first generation will all be heterozygous (have two different alleles) • One of the alleles is able to block the other (yellow is dominant vs. green is recessive) • The F1’s pass on both of their alleles in a random manner • Mendel’s Law of Segregation – the alleles for a trait separate randomly during gamete formation and reunite at fertilization

33. Mendelian Inheritance • Mendel’s results held true for other plants (corn, beans) • They can also be generalized to any sexually reproducing organism including humans

34. Mendelian Inheritance • Humans don’t typically have families large enough to see mendelian ratios • Inheritance can be tracked through the use of pedigrees • Are the traits in white and black dominant or recessive?

35. Mendelian Inheritance • If the trait indicated in black is dominant we would expect the cross between 2 and 3 to produce either 100% black trait offspring or ~50% black trait and ~50% white trait offspring • That ain’t the case BB bb Bb Bb Bb Bb Bb Bb Bb bb Bb bb bb bb Bb Bb

36. Mendelian Inheritance • If the trait indicated in black is recessive we would expect the cross between 2 and 3 to produce all white trait offspring • Although it is possible for individual 3 to have a Bb genotype, it is unlikely (0.56 = 0.016) • What is the genotype of #2’s sister? bb BB Bb Bb Bb Bb Bb Bb

37. B? B? B? Bb Bb bb Bb Bb bb Bb Bb bb bb bb bb bb bb Mendelian Inheritance • Using the information from the previous slides we can deduce most individual’s genotypes Bb BB bb Bb Bb Bb Bb Bb Bb

38. Mendelian Inheritance • The examples above are referred to as monohybrid crosses since they deal with only one trait at a time • Mendel also followed dihybrid crosses in which two traits are followed at once • Would the traits segregate as a single unit or independently?

39. Mendelian Inheritance • A dihybrid cross

41. Mendelian Inheritance • A dihybrid cross produced all possible phenotypes and genotypes • Thus, all of the alleles behaved independently of one another • Mendel’s Law of Independent Assortment – Each pair of alleles segregates independently during gamete formation

42. Mendelian Inheritance • Mendel’s Laws of Segregation and Independent Assortment are a result of the process of meiosis • During meiosis, the chromosomes that carry alleles are distributed randomly among the resulting gametes • The law of segregation • Traits (genes) residing on one chromosome are distributed independently of those on other chromosomes • The law of independent assortment

43. DNA Analysis: DNA Cloning

44. Mendelian Inheritance • Mendel’s Laws of Segregation and Independent Assortment are a result of the process of meiosis • During meiosis, the chromosomes that carry alleles are distributed randomly among the resulting gametes • The law of segregation • Traits (genes) residing on one chromosome are distributed independently of those on other chromosomes • The law of independent assortment • What about genes that reside on the same chromosome? Do they also assort independently?

45. Mendelian Inheritance • Yes, generally genes on the same chromosome behave just like genes on different chromosomes – they assort independently • How? • Remember recombination and crossing-over?

46. Mendelian Inheritance Typically, several cross-over events will occur between well-separated genes on the same chromosome. Therefore, genes E and F or D and F are no more likely to be co-inherited than genes on different chromosomes. Genes that are very close together (A and B), on the other hand, are less likely to have cross-over events occur between them. Thus, they will often be co-inherited (linked) and do not strictly follow the Law of Independent Assortment.

47. Non-Mendelian Inheritance: Linkage Maps • By following the rates of recombination between genes on the same chromosome, we can determine where they are in relation to each other • The results of these studies is called a linkage map • Linkage maps are based on the frequency with which two genes are co-inherited. The closer they are to each other, the more often they are co-inherited.

48. DNA Analysis: Nucleic Acid Hybridization

49. Mendelian Inheritance: Genotypes and Phenotypes • The genotype has an effect on the phenotype but not vice-versa • Heterozygotes tell us whether an allele is dominant or recessive • Heterozygotes harbor two alternative alleles of a gene • Why does the allele for round peas (dominant) mask the effect of the allele for wrinkled peas (recessive)? RR rr Rr Rr Rr Rr Rr

50. Mendelian Inheritance: Genotypes and Phenotypes • The gene in question encodes an enzyme that converts sugars into starch • ‘R’ is the active allele, ‘r’ is an allele that doesn’t encode an active enzyme (a loss-of-function mutant) • RR genotype > both alleles produce active enzyme > round pea phenotype • rr genotype > neither allele produces active enzyme > wrinkled pea phenotype • Rr genotype > the active allele produces enough enzyme to overcome the enzyme deficiency > round pea phenotype