4-1Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Powerpoint to accompany Genetics: From Genes to Genomes Third

4-1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display

Powerpoint to accompany

Genetics: From Genes to GenomesThird Edition

Hartwell ● Hood ● Goldberg ● Reynolds ● Silver ● Veres

Chapter4

Prepared by Malcolm SchugUniversity of North Carolina Greensboro


The Chromosome Theory of The Chromosome Theory of InheritanceInheritance


Outline of Chromosome Outline of Chromosome Theory of InheritanceTheory of Inheritance

Observations and experiments that placed Observations and experiments that placed the hereditary material in the nucleus on the the hereditary material in the nucleus on the chromosomeschromosomes

Mitosis ensures that every cell in an Mitosis ensures that every cell in an organism carries same set of chromosomes.organism carries same set of chromosomes.

Meiosis distributes one member of each Meiosis distributes one member of each chromosome pair to gamete cells.chromosome pair to gamete cells.

Gametogenesis, the process by which germ Gametogenesis, the process by which germ cells differentiate into gametescells differentiate into gametes

Validation of the chromosome theory of Validation of the chromosome theory of inheritanceinheritance


Evidence that Genes Reside Evidence that Genes Reside in the Nucleusin the Nucleus

1667 – Anton van Leeuwenhoek1667 – Anton van Leeuwenhoek MicroscopistMicroscopist Semen contains spermatozoa (sperm Semen contains spermatozoa (sperm

animals).animals). Hypothesized that sperm enter egg to achieve Hypothesized that sperm enter egg to achieve

fertilizationfertilization 1854-1874 – confirmation of fertilization 1854-1874 – confirmation of fertilization

through union of eggs and spermthrough union of eggs and sperm Recorded frog and sea urchin fertilization Recorded frog and sea urchin fertilization

using microscopy and time-lapse drawings using microscopy and time-lapse drawings and micrographsand micrographs


Evidence that Genes Reside Evidence that Genes Reside in Chromosomesin Chromosomes

1880s – innovations in microscopy and 1880s – innovations in microscopy and staining techniques identified thread-like staining techniques identified thread-like structuresstructures

Provided a means to follow movement of Provided a means to follow movement of chromosomes during cell divisionchromosomes during cell division

Mitosis – two daughter cells contained Mitosis – two daughter cells contained same number of chromosomes as parent same number of chromosomes as parent cell (somatic cells)cell (somatic cells)

Meiosis – daughter cells contained half Meiosis – daughter cells contained half the number of chromosomes as the the number of chromosomes as the parents (sperm and eggs)parents (sperm and eggs)


One Chromosome Pair One Chromosome Pair Determines an Individual’s Determines an Individual’s

Sex.Sex. Walter Sutton – Studied great lubber Walter Sutton – Studied great lubber

grasshoppergrasshopper Parent cells contained 22 chromosomes Parent cells contained 22 chromosomes

plus an X and a Y chromosome.plus an X and a Y chromosome. Daughter cells contained 11 Daughter cells contained 11

chromosomes and X or Y in equal chromosomes and X or Y in equal numbers.numbers.


After After fertilization fertilization Cells with XX Cells with XX

were were females.females.

Cells with XY Cells with XY were males.were males.

Great lubber grasshopper

(Brachystola magna)Fig. 4.5


Sex chromosomeSex chromosome Provide basis for Provide basis for

sex sex determinationdetermination

One sex has One sex has matching pair.matching pair.

Other sex has Other sex has one of each type one of each type of chromosome.of chromosome.

Photomicrograph of humanX and Y chromosome

Fig. 4.6a


Sex Sex determination determination in humansin humans Children Children

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

Fig. 4.6b


At Fertilization, Haploid At Fertilization, Haploid Gametes Produce Diploid Gametes Produce Diploid

Zygotes.Zygotes. Gamete contains one-half the number Gamete contains one-half the number

of chromosomes as the zygote.of chromosomes as the zygote. Haploid – cells that carry only a single Haploid – cells that carry only a single

chromosome setchromosome set Diploid – cells that carry two matching Diploid – cells that carry two matching

chromosome setschromosome sets n – the number of chromosomes in a n – the number of chromosomes in a

haploid cellhaploid cell 2n – the number of chromosomes in a 2n – the number of chromosomes in a

diploid celldiploid cell


diploid vs diploid vs haploid cell in haploid cell in

Drosophila Drosophila

melanogastermelanogaster

Fig. 4.2


The number and shape of The number and shape of chromosomes vary from chromosomes vary from

species to species.species to species.OrganismOrganism nn 2n2n

Drosophila melanogasterDrosophila melanogaster 44 88

Drosophila obscuraDrosophila obscura 55 1010

Drosophila virilusDrosophila virilus 66 1212

PeasPeas 77 1414

Macaroni wheatMacaroni wheat 1414 2828

Giant sequoia treesGiant sequoia trees 1111 2222

GoldfishGoldfish 4747 9494

DogsDogs 3939 7878

HumansHumans 2323 4646


Anatomy of a Anatomy of a chromosomechromosome

Metaphase chromosomes are classified by the position of the centromereFig. 4.3


Homologous chromosomes Homologous chromosomes match in size, shape, and match in size, shape, and

banding patterns.banding patterns. Homologous chromosomes Homologous chromosomes

(homologs) contain the same set of (homologs) contain the same set of genes.genes.

Genes may carry different alleles.Genes may carry different alleles. Nonhomologous chromosomes carry Nonhomologous chromosomes carry

completely unrelated sets of genes.completely unrelated sets of genes.


Karyotypes can be produced by Karyotypes can be produced by cutting micrograph images of cutting micrograph images of

stained chromosomes and stained chromosomes and arranging them in matched pairsarranging them in matched pairs

Human male karyotypeFig 4.4


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

Note 22 pairs of autosomes and 1 pair of sex chromosomes


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


XXXXXX XXXX XXYXXY XOXO XYXY XYYXYY OYOY

DrosophDrosophilaila

DiesDies Normal Normal femalefemale

Normal Normal femalefemale

Sterile Sterile malemale

Normal Normal malemale


DiesDies

HumansHumansNearly Nearly normalnormal

femalefemale

Normal Normal femalefemale

Kleinfelter Kleinfelter male male

(sterile); (sterile); tall, thintall, thin

Turner Turner female female

(sterile); (sterile); webbed webbed

neckneck


Normal Normal or nearly or nearly normal normal

malemale

DiesDies

Complement of sex chromosomesHumans – presence of Y determines sex

Drosophila – ratio of autosomes to X chromosomes determines sex


Mitosis ensures that every cell Mitosis ensures that every cell in an organism carries the in an organism carries the

same chromosomes.same chromosomes. Cell cycle – repeating pattern of cell Cell cycle – repeating pattern of cell

growth and divisiongrowth and division Alternates between interphase and Alternates between interphase and

mitosismitosis Interphase – period of cell cycle Interphase – period of cell cycle

between divisions/cells grow and between divisions/cells grow and replicate chromosomesreplicate chromosomes G1 – gap phase – birth of cell to onset of G1 – gap phase – birth of cell to onset of

chromosome replication/cell growthchromosome replication/cell growth S – synthesis phase – duplication of DNAS – synthesis phase – duplication of DNA G2 – gap phase – end of chromosome G2 – gap phase – end of chromosome

replication to onset of mitosisreplication to onset of mitosis


The cell cycle

Fig. 4.7a


Chromosome replication Chromosome replication during S phase of cell cycleduring S phase of cell cycle

Synthesis of chromosomes

Note the formation of sister chromatids

Fig. 4.7 b


InterphaseInterphase

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

synthesis, chromosome replicationsynthesis, chromosome replication Outside of nucleusOutside of nucleus

Formation of microtubules radiating out Formation of microtubules radiating out into cytoplasm crucial for interphase into cytoplasm crucial for interphase processesprocesses Centrosome – organizing center for Centrosome – organizing center for

microtubules located near nuclear envelopemicrotubules located near nuclear envelope Centrioles – pair of small darkly stained bodies Centrioles – pair of small darkly stained bodies

at center of centrosome in animals (not found in at center of centrosome in animals (not found in plants)plants)


Mitosis – Sister chromatids Mitosis – Sister chromatids separateseparate

Prophase – chromosomes condenseProphase – chromosomes condense Inside nucleusInside nucleus

Chromosomes condense into structures suitable for replication.Chromosomes condense into structures suitable for replication. Nucleoli begin to break down and disappear.Nucleoli begin to break down and disappear.

Outside nucleusOutside nucleus Centrosomes which replicated during interphase move apart Centrosomes which replicated during interphase move apart

and migrate to opposite ends of the nucleus.and migrate to opposite ends of the nucleus. Interphase microtubules disappear and are replaced by Interphase microtubules disappear and are replaced by

microtubules that rapidly grow from and contract back to microtubules that rapidly grow from and contract back to centrosomal organizing centers.centrosomal organizing centers.

Fig. 4.8 a


Mitosis - continuedMitosis - continued

PrometaphasePrometaphase Nuclear envelope breaks downNuclear envelope breaks down Microtubules invade nucleusMicrotubules invade nucleus Chromosomes attach to microtubules through Chromosomes attach to microtubules through

kinetochorekinetochore Mitotic spindle – composed of three types of microtubulesMitotic spindle – composed of three types of microtubules

Kinetochore microtubules – centrosome to kinetochoreKinetochore microtubules – centrosome to kinetochore Polar microtubules – centrosome to middle of cellPolar microtubules – centrosome to middle of cell Astral microtubules – centrosome to cell’s peripheryAstral microtubules – centrosome to cell’s periphery

Fig. 4.8b



Metaphase – middle stageMetaphase – middle stage Chromosomes move towards imaginary Chromosomes move towards imaginary

equator called metaphase plateequator called metaphase plate

Fig. 4.8 c



AnaphaseAnaphase Separation of sister chromatids allows each Separation of sister chromatids allows each

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

Fig. 4.8 d


Mitosis – continuedMitosis – continued

TelophaseTelophase Spindle fibers disperseSpindle fibers disperse Nuclear envelope forms around group of chromosomes at Nuclear envelope forms around group of chromosomes at

each poleeach pole One or more nucleoli reappearOne or more nucleoli reappear Chromosomes decondenseChromosomes decondense Mitosis completeMitosis complete

Fig. 4.8 e



Cytokinesis - cytoplasm dividesCytokinesis - cytoplasm divides Starts during anaphase and ends in telophaseStarts during anaphase and ends in telophase Animal cells – contractile ring pinches cells into two Animal cells – contractile ring pinches cells into two

halveshalves Plant cells – cell plate forms dividing cell into two halves Plant cells – cell plate forms dividing cell into two halves

Fig. 4.8 f


CheckpoiCheckpoints help nts help regulate regulate cell cyclecell cycle

Fig. 4.11


Meiosis produces haploid Meiosis produces haploid germ cells.germ cells.

Somatic cells – divide mitotically and Somatic cells – divide mitotically and make up vast majority of organism’s make up vast majority of organism’s tissuestissues

Germ cells – specialized role in the Germ cells – specialized role in the production of gametesproduction of gametes Arise during embryonic development in Arise during embryonic development in

animals and floral development in plantsanimals and floral development in plants Undergo meiosis to produce haploid Undergo meiosis to produce haploid

gametesgametes Gametes unite with gamete from opposite Gametes unite with gamete from opposite

sex to produce diploid offspring.sex to produce diploid offspring.


MeiosisMeiosisChromosomes replicate Chromosomes replicate

once.once.Nuclei divide twice.Nuclei divide twice.

Fig. 4.12


Meiosis – Prophase IMeiosis – Prophase I

Feature Figure 4.13


Meiosis – Prophase I Meiosis – Prophase I continuedcontinued


Crossing over during Crossing over during prophase produces prophase produces

recombined chromosomes.recombined chromosomes.

Fig. 4.14 a-c

4-35 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or displayFig. 4.14 d, e


How crossing over produces How crossing over produces recombined gametesrecombined gametes

Fig. 4.15


Meiosis I – Metaphase and Meiosis I – Metaphase and AnaphaseAnaphase


Meiosis – Telophase I and Meiosis – Telophase I and InterkinesisInterkinesis


Meiosis – Prophase II and Meiosis – Prophase II and Metaphase IIMetaphase II


Meiosis – Anaphase II and Meiosis – Anaphase II and Telophase IITelophase II


Meiosis - CytokenesisMeiosis - Cytokenesis

Fig. 4.13


Meiosis contributes to Meiosis contributes to genetic diversity in two genetic diversity in two

ways.ways. Independent assortment of Independent assortment of

nonhomologous chromosomes nonhomologous chromosomes creates different combinations of creates different combinations of alleles among chromosomes.alleles among chromosomes.

Crossing-over between homologous Crossing-over between homologous chromosomes creates different chromosomes creates different combinations of alleles within each combinations of alleles within each chromosome.chromosome.

4-43 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or displayFig. 4.17


Gametogenesis involved Gametogenesis involved mitosis and meiosis.mitosis and meiosis.

Oogenesis – egg formation in humansOogenesis – egg formation in humans Diploid germ cells called oogonia multiply Diploid germ cells called oogonia multiply

by mitosis to produce primary oocytes.by mitosis to produce primary oocytes. Primary oocytes undergo meiosis I to Primary oocytes undergo meiosis I to

produce one secondary oocyte and one produce one secondary oocyte and one small polar body (which arrests small polar body (which arrests development).development).

Secondary oocyte undergoes meiosis II to Secondary oocyte undergoes meiosis II to produce one ovum and one small polar produce one ovum and one small polar body.body.

Polar bodies disintegrate leaving one large Polar bodies disintegrate leaving one large functional gametefunctional gamete


Oogenesis in humansOogenesis in humans

Fig 4.18


GametogenesisGametogenesis Spermatogenesis in humansSpermatogenesis in humans

Symmetrical meiotic divisions produce four Symmetrical meiotic divisions produce four functional sperm.functional sperm.

Begins in male testis in germ cells called Begins in male testis in germ cells called spermatogoniaspermatogonia

Mitosis produces diploid primary Mitosis produces diploid primary spermatocytes.spermatocytes.

Meiosis I produces two secondary Meiosis I produces two secondary spermatocytes per cell.spermatocytes per cell.

Meiosis II produces four equivalent Meiosis II produces four equivalent spermatids.spermatids.

Spematids mature into functional sperm.Spematids mature into functional sperm.


Spermatogenesis in Spermatogenesis in humanshumans

Fig. 4.19


The chromosome theory correlates The chromosome theory correlates Mendel’s laws with chromosome Mendel’s laws with chromosome

behavior during meiosis.behavior during meiosis.Chromosome BehaviorChromosome Behavior

Each cell contains two copies of each Each cell contains two copies of each chromosomechromosome

Chromosome complements appear Chromosome complements appear unchanged during transmission from unchanged during transmission from parent to offspring.parent to offspring.

Homologous chromosomes pair and Homologous chromosomes pair and then separate to different gametes.then separate to different gametes.

Maternal and paternal copies of Maternal and paternal copies of chromosome pairs separate without chromosome pairs separate without regard to the assortment of other regard to the assortment of other homologous chromosome pairs.homologous chromosome pairs.

At fertilization an egg’s set of At fertilization an egg’s set of chromosomes unite with randomly chromosomes unite with randomly encountered sperm’s chromosomes.encountered sperm’s chromosomes.

In all cells derived from a fertilized In all cells derived from a fertilized egg, one half of chromosomes are of egg, one half of chromosomes are of maternal origin, and half are paternal.maternal origin, and half are paternal.

Behavior of genesBehavior of genes Each cell contains two copies of Each cell contains two copies of

each gene.each gene. Genes appear unchanged during Genes appear unchanged during

transmission from parent to transmission from parent to offspring.offspring.

Alternative alleles segregate to Alternative alleles segregate to different gametes.different gametes.

Alternative alleles of unrelated Alternative alleles of unrelated genes assort independentlygenes assort independently..

Alleles obtained from one parent Alleles obtained from one parent unite at random with those from unite at random with those from another parent.another parent.

In all cells derived from a fertilized In all cells derived from a fertilized gamete, one half of genes are of gamete, one half of genes are of maternal origin, and half are maternal origin, and half are paternal.paternal.


Specific traits are Specific traits are transmitted with specific transmitted with specific

chromosomes.chromosomes. A test of the chromosome theoryA test of the chromosome theory

If genes are on specific chromosomes, If genes are on specific chromosomes, then traits determined by the gene should then traits determined by the gene should be transmitted with the chromosome.be transmitted with the chromosome.

T.H. Morgan’s experiments demonstrating T.H. Morgan’s experiments demonstrating sex-linked inheritance of a gene sex-linked inheritance of a gene determining eye-color demonstrate the determining eye-color demonstrate the transmission of traits with chromosomes.transmission of traits with chromosomes.

1910 – T.H. Morgan discovered a white – 1910 – T.H. Morgan discovered a white – eyed male, eyed male, Drosophila melanogaster,Drosophila melanogaster, among his stocks.among his stocks.


Nomenclature for Nomenclature for Drosophila geneticsDrosophila 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


Gene symbol is chosen arbitrarilyGene symbol is chosen arbitrarily e.g., Cy is curly winged, v is vermilion eyed, e.g., Cy is curly winged, v is vermilion eyed,

etc.etc. Cy, Sb, D are dominant (upper case Cy, Sb, D are dominant (upper case

letter).letter). vg, y, e, are recessive (lower case letter).vg, y, e, are recessive (lower case letter). vg+ - wild-type recessive allele for vg+ - wild-type recessive allele for

vestigial gene locusvestigial gene locus Cy+ - wild-type dominant allele for curly Cy+ - wild-type dominant allele for curly

gene locusgene locus

Examples of notations Examples of notations for Drosophilafor Drosophila


Criss-cross Criss-cross inheritance inheritance of the white of the white

gene gene demonstrates demonstrates

X-linkage.X-linkage.

Fig. 4.20


Rare events Rare events of of

nondisjunctinondisjunction in XX on in XX female female

produce XX produce XX and O eggs.and O eggs.

Segregation in an XX female

Fig. 4.21 a


Segregation in an XXY female

Fig. 4.21 b


X and Y linked traits in X and Y linked traits in humans are identified by humans are identified by

pedigree analysis.pedigree analysis. X-linked traits exhibit five characteristics X-linked traits exhibit five characteristics

seen in pedigrees.seen in pedigrees. Trait appears in more males than females.Trait appears in more males than females. Mutation and trait never pass from father to Mutation and trait never pass from father to

son.son. Affected male does pass X-linked mutation to Affected male does pass X-linked mutation to

all daughters, who are heterozygous carriers.all daughters, who are heterozygous carriers. Trait often skips a generation.Trait often skips a generation. Trait only appears in successive generations Trait only appears in successive generations

if sister of an affected male is a carrier. If so, if sister of an affected male is a carrier. If so, one half of her sons will show trait.one half of her sons will show trait.


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

Fig. 4.23 a


Example of sex-linked Example of sex-linked dominant trait in human dominant trait in human

pedigree – hypophosphatemiapedigree – hypophosphatemia

Fig. 4.23 b

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4-1Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Powerpoint to accompany Genetics: From Genes to Genomes Third