Lecture 3 The chromosome theory of inheritance

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Genetics 2008

Lectured by Han-Jia Lin

Lecture 3

The chromosome theory of inheritance

http://hanjia.km.ntou.edu.tw

Lectured by

Han-Jia Lin

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Genetics 2008


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

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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 4

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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)

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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.

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• After fertilization• Cells with XX

were females.• Cells with XY

were males.

Great lubber grasshopper(Brachystola magna)

Fig. 4.5

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• Sex chromosome• Provide basis for

sex determination• One sex has

matching pair.• Other sex has one

of each type of chromosome.

Photomicrograph of humanX and Y chromosome

Fig. 4.6a8

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• Sex determinationin humans• Children

receive only an X chromosome from mother but X or Y from father.

Fig. 4.6b

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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 10

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diploid vs haploid cell in

Drosophilamelanogaster

Fig. 4.2

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The number and shape of chromosomes vary from species to species.

4623Humans7839Dogs9447Goldfish2211Giant sequoia trees2814Macaroni wheat147Peas126Drosophila virilus105Drosophila obscura84Drosophila melanogaster

2nnOrganism

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Anatomy of a chromosome

Metaphase chromosomes are classified by the position of the centromere

Fig. 4.3

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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.

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Karyotypes can be produced by cutting micrograph images of stained chromosomes and

arranging them in matched pairs

Human male karyotypeFig 4.4

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Autosomes – pairs of nonsex chromosomesSex chromosomes and autosomes are arranged in homologous pairs

Note 22 pairs of autosomes and 1 pair of sex chromosomes 16

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There is variation between species in how chromosomes determine an individual’s

sex.

__________________________________________________

Chromosome Females Males Organism__________________________________________________

XX-XY XX XY Mammals, DrosophilaXX-XO XX XO GrasshoppersZZ-ZW ZW ZZ Fish, Birds, Moths__________________________________________________

Table 4.1

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DiesNormalor

nearlynormal

male

Normalmale

Turnerfemale

(sterile);webbed

neck

Kleinfelter male

(sterile);tall, thin

Normalfemale

Nearlynorma

lMale

Humans

DiesNormalmale

Normalmale

Sterilemale

Normalfemale

Normalfemale

DiesDrosophila

OYXYYXYXOXXYXXXXX

Complement of sex chromosomesHumans – presence of Y determines sex

Drosophila – ratio of autosomes to X chromosomes determines sex

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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

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The cell cycle

Fig. 4.7a20

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Chromosome replication during S phase of cell cycle

Synthesis of chromosomes

Note the formation of sister chromatids

Fig. 4.7 b

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Interphase

• Within nucleus• G1, S, and G2 phase – cell growth, protein

synthesis, chromosome replication• Outside of nucleus

• Formation of microtubules radiating out into cytoplasm crucial for interphaseprocesses

• 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) 22

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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

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Mitosis - continued

• 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

Fig. 4.8b

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Mitosis - continued

• Metaphase – middle stage• Chromosomes move towards imaginary equator

called metaphase plate

Fig. 4.8 c

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Mitosis - continued

• Anaphase• Separation of sister chromatids allows each

chromatid to be pulled towards spindle pole connected to by kinetochore microtubule.

Fig. 4.8 d26

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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

Fig. 4.8 e

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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

halvesFig. 4.8 f

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Checkpointshelp regulate

cell cycle

Fig. 4.11

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Meiosis produces haploid germ cells.

• Somatic cells – divide mitotically and make up vast majority of organism’stissues

• Germ cells (germ line) – 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.30

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MeiosisChromosomes replicate once.

Nuclei divide twice.

Fig. 4.12

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Meiosis – Prophase I

Feature Figure 4.13 32

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Meiosis – Prophase I continued

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Crossing over during prophase produces recombined chromosomes.

Fig. 4.14 a-c34

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Lectured by Han-Jia LinFig. 4.14 d, e

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How crossing over produces recombined gametes

Fig. 4.15 36

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Meiosis I – Metaphase and Anaphase

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Meiosis – Prophase II and Metaphase II

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Meiosis – Prophase II and Metaphase II

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Meiosis – Anaphase II and Telophase II

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Meiosis – Telophase I and Interkinesis

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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.

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Lectured by Han-Jia LinFig. 4.17

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Hybrid sterility

• Hibrid animals carry nonhomologouschromosomes,which can not pair up!

• Mule : donkey father and horse mother

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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

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Oogenesis in humans

Fig 4.18 46

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Oogenesis in human• Asymmetric division:

• polar body (5% cytosol); primary oocyte (95%)• Discontinue division:

• Fetal stage (~6 month): • 500,000 primary oocyte were produced• Arrested in diplotene of meiosis I

• Puberty• Release 1 primary oocyte per cycle (~480/life)• Complete meiosis I to metaphase of meiosis II

• Fertilization• After sperm penetrating, the oocyte completes meiosis II

quickly• Sperm nucleus and oocyte nucleus fused

• Meiotic segregational errors: depend on age

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Nondisjuction in human

• Trisomy• Usually lethal

• Down syndrome• Trisomy 21

• Klinefelter syndrome• Trisomy X

• Amniocentesis• Exam amniocytes

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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.

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Spermatogenesis in humans

Fig. 4.19 50

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The chromosome theory correlates Mendel’s laws with chromosome behavior during meiosis.

Chromosome Behavior• 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.

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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.

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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

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• 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

Examples of notations for Drosophila

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Lectured by Han-Jia LinFig. 4.20

• Crisscrossinheritance of the white gene demonstratesX-linkage.

• Male is “hemizygous”

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Segregation in an XX female

Fig. 4.21 a

• Rare events of nondisjunction in XX female produce XX and O eggs.

• 1/2000• By Calvin Bridge

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Segregation in an XXY female

Fig. 4.21 b

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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.

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Daltonian

• 8% in male; 0.44% in female

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Example of sex-linked recessive trait in human pedigree – hemophilia

Fig. 4.23 a60

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Example of sex-linked dominant trait in human pedigree – hypophosphatemia

Fig. 4.23 b

• Affected father has affected daughter• Affected mother has 50% affected

children

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Autosomal Genes Can Also Affect Phenotypic Differences Between Sexs

• Sex-limited traits• Stuck mutant in Drosophia

• Sex-influenced traits• Pattern baldness

• Heterozygous: Male bald; Female normal• Homozygous: Male early bald; Female late!

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Lecture 3 The chromosome theory of inheritance