Chapter 4: The Chromosome Theory of Inheritance

Chapter 4: The Chromosome Theory of Inheritance Chapter of the textbook: Genetics: From Genes to Genomes, 4th edition (2011), Hartwell H et al CHAPTER OUTLINE: 4.1 Chromosomes: The Carriers of Genes 4.2 Mitosis: Cell Division That Preserves Chromosome Number 4.3 Meiosis: Cell Divisions That Halve Chromosome Number 4.4 Gametogenesis 4.5 Validation of the Chromosome Theory VNU-University of Science - DNThai Down syndrome: One extra chromosome 21 has widespread phenotypic consequences Trisomy 21, gives rise to an abnormal phenotype, including a wide skull, an unusually large tongue, learning disabilities, as well as heart disorders, rapid aging, and leukemia How can one extra copy of a chromosome that is itself of normal size and shape cause such wide-ranging phenotypic effects? VNU-University of Science - DNThai http://anthro.palomar.edu/abnor mal/images/Down_Syndrome_ Karyotype.jpg 4.1 Chromosomes: The Carriers of Genes Evidence that Genes Reside in the Nucleus • 1667 – Anton van Leeuwenhoek – Microscopist – Semen contains spermatozoa (sperm animals) – Hypothesized that sperm enter egg to achieve fertilization • 1854-1874 – confirmation of fertilization through union of eggs and sperm, main parts are their nuclei – Recorded frog and sea urchin fertilization using microscopy and time-lapse drawings and micrographs VNU-University of Science - DNThai Genes reside in chromosomes • 1880s – innovations in microscopy and staining techniques identified thread-like structures • Provided a means to follow movement of chromosomes during cell division • Mitosis - nuclear division that generates two daughter cells containing the same number and type of chromosomes as parent cell • Meiosis - Nuclear division that generates gametes (egg and sperm) containing half the number of chromosomes found in other cells VNU-University of Science - DNThai Fertilization: The union of haploid gametes to produce diploid zygotes • Fertilized eggs carry matching sets of chromosomes, one set from maternal gamete and one set from paternal gamete • Gametes are haploid (n) – carry only a single set of chromosomes • Zygotes are diploid (2n) – carry two matching set of chromosome • Mitosis ensures that all cells of developing individuals have identical 2n chromosome sets VNU-University of Science - DNThai Diploid versus haploid: 2n versus n Most body cells are diploid (each chromosome pair has one maternal and one paternal copy) Meiosis  haploid (n) gametes In Drosophila, 2n = 8, n = In humans , 2n = 46 and n = 23 Fig 4.2 VNU-University of Science - DNThai Nomenclature for Drosophila genetics • Homologous chromosomes contain the same set of genes, but can have different alleles for some genes • Nonhomologous chromosomes carry completely unrelated sets of genes Fig 4.3 VNU-University of Science - DNThai Karyotype of a human male • Karyotype – micrograph of stained chromosomes arranged in homologous pairs – Sex chromosomes – unpaired X and Y chromosome – Autosomes – all chromosomes except X and Y • Each homologous pair arranged in order of decreasing size Fig 4.4 VNU-University of Science - DNThai Sex chromosomes: one chromosome pair determines sex in grasshoppers • W S Sutton studied meiosis in great lubber grasshoppers • Before meiosis, testes cells had 24 chromosomes – 22 in matched pairs (autosomes) and unmatched (large = X and smaller = Y) • After meiosis, two types of sperm were formed and separated: – 1/2 of sperm had 11 chromosomes and an X – 1/2 of sperm had 11 chromosomes and a Y • After meiosis, only one type of egg was produced – All had 11 chromosomes plus an X • Then Sutton did the fertilization as follow: VNU-University of Science - DNThai The great lubber grasshopper • Fertilization of egg with sperm carrying an X  XX female • Fertilization of egg with sperm carrying a Y  XY male • Sutton concluded that the X and Y chromosomes determine sex The great lubber grasshoppers (Brachystola magna) In this mating pair, the smaller male is astride the female Fig 4.5 VNU-University of Science - DNThai 10 Mapping genes by comparisons of two-point crosses • Left-right orientation of map is arbitrary • Most accurate maps obtained by summing many small intervening distances VNU-University of Science - DNThai Fig 5.9 72 Limitations of two point crosses • Difficult to determine gene order if two genes are close together • Actual distances between genes not always add up • Pairwise crosses are time and labor consuming VNU-University of Science - DNThai 73 Three point crosses provide faster and more accurate mapping • Testcross of triply-heterozygous F1 VNU-University of Science - DNThai Fig 5.10 74 Analyzing the results of a three-point cross Testcross progeny have four sets of reciprocal pairs of genotypes • Most frequent pair has parental configuration of alleles • Least frequent pair results from double crossovers • Examination of double crossover class reveals which gene is in the middle VNU-University of Science - DNThai Fig 5.10 75 Inferring the location of crossover event • Examine numbers of progeny • Compare configuration of alleles at two genes at a time to parental configuration Fig 5.11a VNU-University of Science - DNThai 76 Inferring the location of crossover events (cont) VNU-University of Science - DNThai Fig 5.11b-c-d 77 Genetic map deduced from three-point cross in Figure 5.10 ฀ ฀ vg - b distance = (252+ 241+ 131+ 118) x 100  17.7 4197 vg - pr distance = (252+ 241+ 13 + 9) x 100  12.3 4197 (131+ 118+ 13 + 9) b - pr distance = x 100  6.4 4197 ฀ Fig 5.10b VNU-University of Science - DNThai 78 Correction for double crossovers • This calculation isn't accurate because it fails to account for double crossovers vg - b distance (252+ 241+ 131+ 118) x 100  17.7 4197 • Correct calculation that accounts for double crossovers vg - b distance (252+ 241+ 131+ 118+ 13 + 13 + + 9) x 100  18.7 4197 VNU-University of Science - DNThai 79 Interference: The number of double crossovers may be less than expected • Chromosomal interference – occurrence of crossover in one portion of a chromosome interferes with crossover in an adjacent part of the chromosome • Not uniform between chromosomes or within a chromosome • Compare observed and expected frequencies of double crossovers (DCO) Coefficient of coincidence = ฀ observed DCO frequency expected DCO frequency Interference = - coefficient of coincidence VNU-University of Science - DNThai 80 Calculation of interference in the threepoint cross in Figure 5.10 • Expected probability of double crossovers is the product of the single crossover frequencies in each interval - Probability of single crossover between vg and pr is 0.123 (12.3 m.u.) - Probability of single crossover between pr and b is 0.064 (6.4 m.u.) • If interference = 0, crossovers in adjacent regions occur independently of each other • If interference = 1, no double crossovers occur VNU-University of Science - DNThai 81 Calculation of interference in the threepoint cross in Figure 5.10 (cont) Expected probability of double crossovers  0.123 x 0.064  0.0079 = 0.79% ฀ Observed proportion of double crossovers  13  x 100  0.52% 4197 0.52 Coefficient of coincidence =  0.66 ฀ 0.79 ฀ Interference  1 0.66  0.34 VNU-University of Science - DNThai 82 Do genetic maps correlate with physical reality? Order of genes revealed by genetic mapping corresponds to the actual order of genes along the chromosome Actual physical distance does not always show direct correspondence to genetic distance – Double, triple, and more crossovers – 50% limit on observable recombination frequency – Non-uniform recombination frequency across chromosomes – Mapping functions compensate for some inaccuracies – Recombination rates differ between species VNU-University of Science - DNThai 83 Drosophila melanogaster has four linkage groups When many genes per chromosome have been mapped, a linkage group is synonymous with a chromosome VNU-University of Science - DNThai Fig 5.13 84 Essential Concepts Gene pairs that are close together on the same chromosome are genetically linked because they are transmitted together more often than not The hallmark of linkage is that the number of parental types is greater than the number of recombinant types among the progeny of double heterozygotes The recombination frequencies of pairs of genes indicate how often two genes are transmitted together For linked genes, the recombination frequency is less than 50% Gene pairs that assort independently exhibit a recombination frequency of 50%, because the number of parental types equals the number of recombinants Genes may assort independently either because they are on different chromosomes or because they are far apart on the same chromosome VNU-University of Science - DNThai 85 Essential Concepts Statistical analysis helps determine whether or not two genes assort independently The probability value (p) calculated by the chi-square test measures the likelihood that a particular set of data supports the null hypothesis of independent assortment, or no linkage The lower the p value, the less likely is the null hypothesis, and the more likely the linkage The greater the physical distance between linked genes, the higher the recombination frequency However, recombination frequencies become more and more inaccurate as the distance between genes increases Recombination occurs because chromatids of homologous chromosomes exchange parts (that is, cross over) during the prophase of meiosis I, after the chromosomes have replicated Genetic maps are a visual representation of relative recombination frequencies The greater the density of genes on the map (and thus the smaller the distance between the genes), the more accurate and useful the map becomes in predicting inheritance VNU-University of Science - DNThai 86 ... humans • Children receive an X chromosome from their mother, but either an X or Y chromosome from their father • Results in 1:1 ratio of females-to-males 11 VNU-University of Science - DNThai Fig 4.6... set of chromosomes • Zygotes are diploid (2n) – carry two matching set of chromosome • Mitosis ensures that all cells of developing individuals have identical 2n chromosome sets VNU-University of. .. 1/2 of sperm had 11 chromosomes and a Y • After meiosis, only one type of egg was produced – All had 11 chromosomes plus an X • Then Sutton did the fertilization as follow: VNU-University of Science