Download Lecture 3 The chromosome theory of inheritance

Genetics 2008
Outline of Chromosome Theory of
Inheritance
Lecture 3
The chromosome theory of
inheritance
Lectured by
Han-Jia Lin
http://hanjia.km.ntou.edu.tw
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• 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
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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
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(sperm and eggs)
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One Chromosome Pair Determines an
Individual’s Sex.
• After
fertilization
• 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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• Cells with XX
were females.
• Cells with XY
were males.
Great lubber grasshopper
(Brachystola magna)
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• Sex chromosome
• Sex
determination
in humans
• Provide basis for
sex determination
• One sex has
matching pair.
• Other sex has one
of each type of
chromosome.
Photomicrograph of human
X and Y chromosome
Fig. 4.6a
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Fig. 4.5Lectured by Han-Jia Lin
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• Children
receive only an
X chromosome
from mother
but X or Y from
father.
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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
diploid vs haploid
cell in
Drosophila
melanogaster
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Fig. 4.2
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The number and shape of chromosomes
vary from species to species.
Organism
Drosophila melanogaster
Drosophila obscura
Drosophila virilus
Peas
Macaroni wheat
Giant sequoia trees
Goldfish
Dogs
Humans
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n
2n
4
5
6
7
14
11
47
39
23
8
10
12
14
28
22
94
78
46
11
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Anatomy of a chromosome
Metaphase chromosomes are classified by the position of the centromere
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Homologous chromosomes match in
size, shape, and banding patterns.
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Karyotypes can be produced by cutting
micrograph images of stained chromosomes and
arranging them in matched pairs
• Homologous chromosomes (homologs)
contain the same set of genes.
• Genes may carry different alleles.
• Nonhomologous chromosomes carry
completely unrelated sets of genes.
Human male karyotype
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Fig 4.4Lectured by Han-Jia Lin
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There is variation between species in how
chromosomes determine an individual’s
sex.
__________________________________________________
Chromosome Females
Males
Organism
__________________________________________________
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
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XX-XY
XX
XY
Mammals, Drosophila
XX-XO
XX
XO
Grasshoppers
ZZ-ZW
ZW
ZZ
Fish, Birds, Moths
__________________________________________________
Table 4.1
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Complement of sex chromosomes
Humans – 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
XXX
XX
XXY
XO
XY
XYY
OY
Dies
Normal
female
Normal
female
Sterile
male
Normal
male
Normal
male
Dies
• Interphase – period of cell cycle between
divisions/cells grow and replicate
chromosomes
Normal
male
Normal
or
nearly
normal
male
Dies
• 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
• Alternates between interphase and mitosis
Drosophila
Humans
Nearly Normal
norma female
l
Male
Kleinfelte Turner
r male
female
(sterile); (sterile);
tall, thin webbed
neck
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Chromosome replication during S
phase of cell cycle
The cell cycle
Synthesis of
chromosomes
Note the
formation of
sister chromatids
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Fig. 4.7a
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Fig. 4.7 b
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Mitosis – Sister chromatids separate
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 interphase
processes
• Prophase – chromosomes condense
• Inside nucleus
• 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
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plants)
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• 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
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centers.
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Mitosis - continued
Mitosis - continued
• Prometaphase
•
•
•
•
Fig. 4.8b
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
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Fig. 4.8 a
• Metaphase – middle stage
• Chromosomes move towards imaginary equator
called metaphase plate
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Mitosis - continued
Mitosis – continued
• Telophase
• Anaphase
•
•
•
•
•
• Separation of sister chromatids allows each
chromatid to be pulled towards spindle pole
connected to by kinetochore microtubule.
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Fig. 4.8 d
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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
Checkpoints
help regulate
cell cycle
• 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
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halves
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Fig. 4.11
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Meiosis
Meiosis produces haploid germ cells.
Chromosomes replicate once.
Nuclei divide twice.
• Somatic cells – divide mitotically and
make up vast majority of organism’s
tissues
• 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.
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Fig. 4.12
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Meiosis – Prophase I
Feature Figure 4.13
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Meiosis – Prophase I continued
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Crossing over during prophase
produces recombined chromosomes.
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Fig. 4.14
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Fig. 4.14
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How crossing over produces
recombined gametes
Fig. 4.15
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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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Gametogenesis involved mitosis and
meiosis.
Hybrid sterility
• Oogenesis – egg formation in humans
• Hibrid animals carry
nonhomologous
chromosomes,
which can not pair
up!
• Mule : donkey father
and horse mother
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Fig. 4.17
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• 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
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functional gamete
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Oogenesis in humans
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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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Fig 4.18
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Gametogenesis
Nondisjuction in human
• Spermatogenesis in humans
• Trisomy
• Usually lethal
• Down syndrome
• Trisomy 21
• Klinefelter syndrome
• Trisomy X
• Amniocentesis
• Exam amniocytes
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• 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. 48
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The chromosome theory correlates Mendel’s laws with
chromosome behavior during meiosis.
Spermatogenesis in humans
•
•
•
•
•
•
Fig. 4.19
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.
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Nomenclature for Drosophila genetics
•
• 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.
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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Examples of notations for
Drosophila
• Crisscross
inheritance of
the white gene
demonstrates
X-linkage.
• Male is
“hemizygous”
• 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
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Fig. 4.20
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Segregation in an
XXY female
• Rare events of
nondisjunction in
XX female
produce XX and
O eggs.
• 1/2000
• By Calvin Bridge
Segregation in an XX female
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Fig. 4.21
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Fig. 4.21
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X and Y linked traits in humans are
identified by pedigree analysis.
Daltonian
• 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.
• 8% in male; 0.44% in female
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Example of sex-linked recessive trait in
human pedigree – hemophilia
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Example of sex-linked dominant trait in
human pedigree – hypophosphatemia
• Affected father has affected daughter
• Affected mother has 50% affected
children
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Fig. 4.23
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Fig. 4.23 b
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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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