Genetics: From Genes to Genomes Powerpoint to accompany Genetics: From Genes to Genomes Third Edition Hartwell ● Hood ● Goldberg ● Reynolds ● Silver ● Veres Chapter 4 Prepared by Malcolm Schug University of North Carolina Greensboro Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

The Chromosome Theory of Inheritance Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Outline of Chromosome Theory of Inheritance Observations and experiments that placed the hereditary material in the nucleus on the chromosomes Mitosis ensures that every cell in an organism carries same set of chromosomes. Meiosis distributes one member of each chromosome pair to gamete cells. Gametogenesis, the process by which germ cells differentiate into gametes Validation of the chromosome theory of inheritance Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

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 Recorded frog and sea urchin fertilization using microscopy and time-lapse drawings and micrographs Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Evidence that 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 – two daughter cells contained same number of chromosomes as parent cell (somatic cells) Meiosis – daughter cells contained half the number of chromosomes as the parents (sperm and eggs) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

One Chromosome Pair Determines an Individual’s Sex. Walter Sutton – Studied great lubber grasshopper Parent cells contained 22 chromosomes plus an X and a Y chromosome. Daughter cells contained 11 chromosomes and X or Y in equal numbers. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Great lubber grasshopper After fertilization Cells with XX were females. Cells with XY were males. Figure 4.2 Great lubber grasshopper (Brachystola magna) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.5

Photomicrograph of human Sex chromosome Provide basis for sex determination One sex has matching pair. Other sex has one of each type of chromosome. Figure 4.3a Photomicrograph of human X and Y chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.6a

Sex determination in humans Children receive only an X chromosome from mother but X or Y from father. Figure 4.3b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.6b

At Fertilization, Haploid Gametes Produce Diploid Zygotes. Gamete contains one-half the number of chromosomes as the zygote. Haploid – cells that carry only a single chromosome set Diploid – cells that carry two matching chromosome sets n – the number of chromosomes in a haploid cell 2n – the number of chromosomes in a diploid cell Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

diploid vs haploid cell in Drosophila melanogaster Figure 4.4 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.2

The number and shape of chromosomes vary from species to species. Organism n 2n Drosophila melanogaster 4 8 Drosophila obscura 5 10 Drosophila virilus 6 12 Peas 7 14 Macaroni wheat 28 Giant sequoia trees 11 22 Goldfish 47 94 Dogs 39 78 Humans 23 46 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Anatomy of a chromosome Figure 4.5 Metaphase chromosomes are classified by the position of the centromere Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.3

Homologous chromosomes match in size, shape, and banding patterns. Homologous chromosomes (homologs) contain the same set of genes. Genes may carry different alleles. Nonhomologous chromosomes carry completely unrelated sets of genes. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Karyotypes can be produced by cutting micrograph images of stained chromosomes and arranging them in matched pairs Figure 4.6 Human male karyotype Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig 4.4

Autosomes – pairs of nonsex chromosomes Sex chromosomes and autosomes are arranged in homologous pairs Note 22 pairs of autosomes and 1 pair of sex chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

There is variation between species in how chromosomes determine an individual’s sex. __________________________________________________ Chromosome Females Males Organism XX-XY XX XY Mammals, Drosophila XX-XO XX XO Grasshoppers ZZ-ZW ZW ZZ Fish, Birds, Moths Table 4.1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Drosophila Humans Complement of sex chromosomes Humans – presence of Y determines sex Drosophila – ratio of autosomes to X chromosomes determines sex XXX XX XXY XO XY XYY OY Drosophila Dies Normal female Sterile male Normal male Humans Nearly normal female Kleinfelter male (sterile); tall, thin Turner female (sterile); webbed neck Normal or nearly normal male Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Mitosis ensures that every cell in an organism carries the same chromosomes. Cell cycle – repeating pattern of cell growth and division Alternates between interphase and mitosis Interphase – period of cell cycle between divisions/cells grow and replicate chromosomes G1 – gap phase – birth of cell to onset of chromosome replication/cell growth S – synthesis phase – duplication of DNA G2 – gap phase – end of chromosome replication to onset of mitosis Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

The cell cycle Fig. 4.7a Figure 4.7a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.7a

Chromosome replication during S phase of cell cycle Synthesis of chromosomes Note the formation of sister chromatids Figure 4.7 b Fig. 4.7 b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Interphase Within nucleus Outside of nucleus G1, S, and G2 phase – cell growth, protein synthesis, chromosome replication Outside of nucleus Formation of microtubules radiating out into cytoplasm crucial for interphase processes Centrosome – organizing center for microtubules located near nuclear envelope Centrioles – pair of small darkly stained bodies at center of centrosome in animals (not found in plants) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Mitosis – Sister chromatids separate Prophase – chromosomes condense Inside nucleus Chromosomes condense into structures suitable for replication. Nucleoli begin to break down and disappear. Outside nucleus Centrosomes which replicated during interphase move apart and migrate to opposite ends of the nucleus. Interphase microtubules disappear and are replaced by microtubules that rapidly grow from and contract back to centrosomal organizing centers. Fig. 4.8 a Figure 4.8 a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Mitosis - continued Prometaphase Nuclear envelope breaks down Fig. 4.8b Prometaphase Nuclear envelope breaks down Microtubules invade nucleus Chromosomes attach to microtubules through kinetochore Mitotic spindle – composed of three types of microtubules Kinetochore microtubules – centrosome to kinetochore Polar microtubules – centrosome to middle of cell Astral microtubules – centrosome to cell’s periphery Figure 4.8 b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Mitosis - continued Metaphase – middle stage Chromosomes move towards imaginary equator called metaphase plate Figure 4.8 c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.8 c

Mitosis - continued Anaphase Separation of sister chromatids allows each chromatid to be pulled towards spindle pole connected to by kinetochore microtubule. Figure 4.8 d Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.8 d

Mitosis – continued Telophase Spindle fibers disperse Nuclear envelope forms around group of chromosomes at each pole One or more nucleoli reappear Chromosomes decondense Mitosis complete Figure 4.8 e Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.8 e

Mitosis - continued Cytokinesis - cytoplasm divides Starts during anaphase and ends in telophase Animal cells – contractile ring pinches cells into two halves Plant cells – cell plate forms dividing cell into two halves Figure 4.8 f Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.8 f

Checkpoints help regulate cell cycle Figure 4.11 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.11

Meiosis produces haploid germ cells. Somatic cells – divide mitotically and make up vast majority of organism’s tissues Germ cells – specialized role in the production of gametes Arise during embryonic development in animals and floral development in plants Undergo meiosis to produce haploid gametes Gametes unite with gamete from opposite sex to produce diploid offspring. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis Chromosomes replicate once. Nuclei divide twice. Figure 4.12 Fig. 4.12 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis – Prophase I Feature Figure 4.13 Feature Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis – Prophase I continued Feature Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Crossing over during prophase produces recombined chromosomes. Figure 4.14 a-c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.14 a-c

Figure 4.14 d, e Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.14 d, e

How crossing over produces recombined gametes Figure 4.15 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.15

Meiosis I – Metaphase and Anaphase Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis – Telophase I and Interkinesis Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis – Prophase II and Metaphase II Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis – Anaphase II and Telophase II Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Meiosis - Cytokenesis Fig. 4.13 Figure 4.13 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.13

Meiosis contributes to genetic diversity in two ways. Independent assortment of nonhomologous chromosomes creates different combinations of alleles among chromosomes. Crossing-over between homologous chromosomes creates different combinations of alleles within each chromosome. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Figure 4.17 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.17

Gametogenesis involved mitosis and meiosis. Oogenesis – egg formation in humans Diploid germ cells called oogonia multiply by mitosis to produce primary oocytes. Primary oocytes undergo meiosis I to produce one secondary oocyte and one small polar body (which arrests development). Secondary oocyte undergoes meiosis II to produce one ovum and one small polar body. Polar bodies disintegrate leaving one large functional gamete Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Oogenesis in humans Fig 4.18 Figure 4.18 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig 4.18

Gametogenesis Spermatogenesis in humans Symmetrical meiotic divisions produce four functional sperm. Begins in male testis in germ cells called spermatogonia Mitosis produces diploid primary spermatocytes. Meiosis I produces two secondary spermatocytes per cell. Meiosis II produces four equivalent spermatids. Spematids mature into functional sperm. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Spermatogenesis in humans Figure 4.19 Fig. 4.19 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

The chromosome theory correlates Mendel’s laws with chromosome behavior during meiosis. Each cell contains two copies of each chromosome Chromosome complements appear unchanged during transmission from parent to offspring. Homologous chromosomes pair and then separate to different gametes. Maternal and paternal copies of chromosome pairs separate without regard to the assortment of other homologous chromosome pairs. At fertilization an egg’s set of chromosomes unite with randomly encountered sperm’s chromosomes. In all cells derived from a fertilized egg, one half of chromosomes are of maternal origin, and half are paternal. Behavior of genes Each cell contains two copies of each gene. Genes appear unchanged during transmission from parent to offspring. Alternative alleles segregate to different gametes. Alternative alleles of unrelated genes assort independently. Alleles obtained from one parent unite at random with those from another parent. In all cells derived from a fertilized gamete, one half of genes are of maternal origin, and half are paternal. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Specific traits are transmitted with specific chromosomes. A test of the chromosome theory If genes are on specific chromosomes, then traits determined by the gene should be transmitted with the chromosome. T.H. Morgan’s experiments demonstrating sex-linked inheritance of a gene determining eye-color demonstrate the transmission of traits with chromosomes. 1910 – T.H. Morgan discovered a white – eyed male, Drosophila melanogaster, among his stocks. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Nomenclature for Drosophila genetics Wild-type allele - allele that is found in high frequency in a population Denoted with a “+” Mutant allele - allele found in low frequency Denoted with no symbol Recessive mutation - gene symbol is in lower case Dominant mutation - gene symbol is in upper case Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Examples of notations for Drosophila Gene symbol is chosen arbitrarily e.g., Cy is curly winged, v is vermilion eyed, etc. Cy, Sb, D are dominant (upper case letter). vg, y, e, are recessive (lower case letter). vg+ - wild-type recessive allele for vestigial gene locus Cy+ - wild-type dominant allele for curly gene locus Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Criss-cross inheritance of the white gene demonstrates X-linkage. Figure 4.20 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.20

Rare events of nondisjunction in XX female produce XX and O eggs. Figure 4.21 a Segregation in an XX female Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.21 a

Segregation in an XXY female Fig. 4.21 b Figure 4.21 b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.21 b

X and Y linked traits in humans are identified by pedigree analysis. X-linked traits exhibit five characteristics seen in pedigrees. Trait appears in more males than females. Mutation and trait never pass from father to son. Affected male does pass X-linked mutation to all daughters, who are heterozygous carriers. Trait often skips a generation. Trait only appears in successive generations if sister of an affected male is a carrier. If so, one half of her sons will show trait. Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Example of sex-linked recessive trait in human pedigree – hemophilia Figure 4.23 a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Fig. 4.23 a

Example of sex-linked dominant trait in human pedigree – hypophosphatemia Figure 4.23 b Fig. 4.23 b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display