Chromosomes: The Physical Basis of Inheritance

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ChromosomesThe Physical Basis of Inheritance

• 1866 Mendel published his work
• 1875 Mitosis was first described
• 1890s Meiosis was described
• 1900 Mendel's work was rediscovered
• 1902 Walter Sutton, Theodore Boveri and others
  noted parallels between behavior of chromosomes
  and alleles.

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Physical basis for Mendels laws Behavior of
chromosomes in meiosis
Physical basis for Mendels laws Behavior of
chromosomes in meiosis
equal segregation of alleles into different
haploid gametes
random assortment of genes on different
chromosomes into gametes
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Chromosomal Theory of Inheritance

• Genes have specific loci on chromosomes.
• Chromosomes undergo segregation (meiosis) and
  independent assortment
• Thus alleles of genes are independently assorted.

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Independent Assortment
As long as genes are on different chromosomes,
they will assort independently
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Chromosomal Basis of Sex

• X-Y system females are homogametic (XX) and
  males are heterogametic (XY) with males and
  females have the same number of chromosomes.
• Examples include humans and all mammals,
  Drosophila.

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• X-O system females are homogametic (XX) and
  males are heterogametic (XO) with males having
  one less chromosome than females.
• Examples include grasshoppers (cavallette),
  crickets (grilli), and cockroaches (scarafaggi).

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• Z-W system males are homogametic (ZZ) and
  females are heterogametic (ZW) with males and
  females have the same number of chromosomes.
• Examples include all birds, some fishes,
  butterflies (farfalle), moths (tarme), and wild
  strawberries (fragole).

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• Haplo-diploidy. There are NO sex chromosomes.
  Fertilized eggs become diploid females.
  Unfertilized eggs become haploid males. Males are
  fatherless.
• Examples are the social insects bees (api), ants
  (formiche), termites (termiti).

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• No sex determination system. Most plants and some
  animals are NOT dioecious organisms with
  separate sexes.
• Most plants some animals are monoecious, where
  the same individual produces both eggs and sperm.
• Examples include earthworms (lombrichi), garden
  snails (lumache), pea plants (piselli) and corn
  (granturco).

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Thomas Hunt Morgan

• First to associate a trait (gene) with a
  chromosome.
• Worked with fruit flies (Drosophila melanogaster)
• Why fruit flies?
• Short generation time (9 days)
• Survives and breeds well in the lab
• Very large chromosomes in some cells
• Many aspects of phenotype are genetically
  controlled.

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Drosophila Mutations
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More Drosophila Mutations
Wild Type
ebony body ee
white eyes ww
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• Normal eye color in Drosophila is red.
• Morgans wife discovered a male Drosophila with
  white eyes on the window in their lab.
• In the parental generation, Morgan crossed this
  male with white eyes to several females with red
  eyes.

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• The offspring of that cross (the F1) all had red
  eyes (both males and females).
• Morgan concluded that white eyes was recessive to
  red eyes.
• Morgan than cross the F1 males and females among
  themselves to produce the F2.

A white-eyed male was discovered
X
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• The phenotypic ratio in the F2 generation was
  75 red and 25 white, which confirmed that red
  was completely dominant to white.
• However, when Morgan looked more carefully at the
  sexes of the flies, he found that all the females
  had red eyes while ½ the males had red and ½ had
  white eyes.

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• P red-eyed female X white-eyed male.
• F1 all red-eyed females males.
• F2 50 red females 25 red males 25 white
  males.
• Conclusion eye color is controlled by gene on the
  X chromosome.
• Males have one X chromosome, while females have
  two X chromosomes.

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Morgans Discovery Of An X-Linked Drosophila Gene
A white-eyed male was discovered
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Notation for Alleles

• White eyes is a recessive mutation.
• When a mutation is recessive, lower case letters
  are used to denote alleles
• Let w white eyes w red eyes.
• The symbol always denotes the normal (wild
  type) phenotype.
• Therefore, female genotypes are ww white eyes
  w w or w w red eyes.

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Notation for Alleles

• Bar eyes is a dominant mutation in Drosophila.
• When a mutation is dominant, upper case letters
  are used to denote alleles
• Let B bar eyes B normal eyes.
• Therefore, female genotypes are BB or BB bar
  eyes BB normal eyes.

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Morgans Crosses - 1

• White eyes is recessive and on the X chromosome
  only.
• P w w (female) x wY (male).
• F1 w w (female) x w Y (male).
• F2 ¼ w w ¼ w w ¼ w Y ¼ wY.
• Females are either homozygous or heterozygous
  while males are hemizygous.

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Morgans Crosses - 2

• Morgan still wanted to obtain white-eyed females.
  To do this, he crossed the F1 females to P males
• w w x wY, which produces in the offspring
• ¼ w w ¼ ww ¼ w Y ¼ wY
• 50 red 50 white

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Note the difference between reciprocal crosses
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The Key To Morgans Discovery

• The key to Morgans discovery was the observation
  that all the white eyed individuals in the F2
  generation were males
• Without this vital data on the association of
  white eyes with being male, the gene for white
  eyes could have been seen as a simple recessive
  trait on an autosome
• This illustrates the importance of recording all
  the data possible and being alert to the
  possibility of interesting things being present
  in the data

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0.05
Bridges experiment
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Unlinked versus Linked Genes

• Unlinked genes are genes located on different
  chromosomes assort independently of each other.
• Linked genes are genes located on the same
  chromosome always assort together unless
  crossing over occurs.

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Meiotic crossing over

• During meiosis, sister chromosomes of homologous
  pairs close pair
• Adjacent arms can transfer identical regions of
  their genes

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How to Determine Whether Genes are Linked or Not

• Testcross the F1 individual.
• If the parental types equal the recombinant types
  (1111), genes are NOT linked.
• If the parental types are significantly greater
  than recombinant types, genes ARE linked.

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assortment 50 recombination
Independent assortment 50 recombination
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X
crossingover
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P PP LL x pp ll
purple flower, long pollen red flower, short
pollen
F
PpLl
1

purple flower, long pollen
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Linked (non-independent) genes
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Most offspring like parents
mom
dad
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Example of Linked Genes - 3

• Recombinants are so much rarer than parental
  types when genes are linked because they are due
  to crossing over.
• Crossing over occurs rarely between the same two
  genes, so the frequency of recombinants is less
  than the frequency of parental types.

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Linkage Groups - 1

• A linkage group is a chromosome.
• Consider the 4 linkage groups below

Genes w, x, and y are linked. Genes c and d are
linked. Genes A and B are not linked, nor is gene
A or gene B linked to the genes in the other
linkage groups (chromosomes). Genes c and d are
not linked to genes w, x, and y.
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Linkage Groups - 2

• If genes are unlinked, they are said to be
  assorting independently.
• If genes are linked they may be
• Partially linked if crossing over is possible, or
• Completely linked if crossing over is not
  possible.

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• Mendel studied loci on separate chromosomes
• Gene loci on the same chromosome are linked
• Their alleles tend to be inherited together
• Crossing over causes linked alleles to be
  unlinked
• Crossing over is very common somewhere among most
  eukaryotes chromosomes (low rate)
• Therefore there are many more possible outcomes

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Chromosome Maps - 1

• In 1917, Alfred Sturtevant, a student of Morgan,
  reasoned that the frequency of crossing over is
  directely related to the distance between the
  genes on the chromosome.
• He used recombination frequencies to position
  genes in correct order on a chromosome (genetic
  map).

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Chromosome Maps - 2

• Sturtevant defined 1 map unit as equivalent to 1
  recombination (centiMorgan)
• Map Distance (MD) 100 X ( recombinants)/(total
  of offspring).
• Example black body and vestigial wings
• MD (206 185)/(965 944 206 185)100
• MD 17.0 map units

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Chromosome Maps - 3

• Recombination frequencies provide information on
  the relative distance between genes along a
  chromosome.
• From this information, it is possible to
  determine the sequence of genes along a
  chromosome (order and distance between each
  consecutive pair).

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Recombination crossing-over
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eye color pr (red) and pr (purple)
wing length vg (normal) and vg (vestigial)
P pr pr vg vg x pr pr vg vg
F
pr pr vg vg
1
pr pr vg vg x
pr pr vg vg
pr vg 1339
pr vg 1195
pr vg 151
pr vg 154
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P pr pr vg vg x pr pr vg vg
pr pr vg vg
F
1
pr pr vg vg x
pr pr vg vg
pr vg 1339
parental
pr vg 1195
pr vg 151
pr vg 154
305 recombinants
10.7
2839 progeny
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P pr pr vg vg x pr pr vg vg
pr pr vg vg
F
1
pr pr vg vg x
pr pr vg vg
pr vg 130
pr vg 121
pr vg 990
pr vg 1094
251 recombinants
10.7
2839 progeny
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TEST A 3 PUNTI
3 mutanti recessivi di Drosophila
v occhi vermilion cv senza crossvein ct ali a
lancia
P / cv/cv ct/ct X v/v / /
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cv ct cv ct
v v
X
P
cv ct v
F
1
v cv ct v cv ct
Cross to triply recessive tester
v 580
Parentali
cv ct 592
v cv 45
Ordine v ct cv
ct 40
v cv ct 89
94
v ct 3
Doppi scambi
cv 5
1448
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1- Individuare le classi più frequenti.
Perchè? Sono i genotipi Parentali in cui non ci
sono stati scambi.
2- Individuare le classi meno frequenti. Perchè?

Il verificarsi simultaneo di 2 crossing over, uno
nel primo intervallo e uno nel secondo, essendo 2
eventi indipendenti, avrà una probabilità pari al
prodotto delle singole probabilità e quindi avrà
un valore inferiore ai singoli.
Le classi meno frequenti rappresentano quindi i
doppi crossing over ( un doppio crossing over ha
come effetto di cambiare la posizione del solo
marcatore centrale)
Noto lassetto parentale e quello dei doppi
scambi, si capisce subito lordine dei geni, cioè
quale sta nel mezzo.
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ct cv ct cv
v v
X
Riscriviamo
P
ct cv v
F
1
89944540/1448 268/1448
18.5
v 580
Parentali
v - cv
ct cv 592
899435191/144813.2
Scambio tra v e ct
v ct cv 89
94
45403593/14486.4
v cv 45
Scambio tra ct e cv
ct 40
v ct 3
Doppi scambi
cv 5
1448
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18.5
v
cv
ct
13.2
6.4
13.2 6.4 19.6 gt 18.5 !! Why ?
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Are multiple crossovers independent ? Example v
13.2 ct 6.4 cv Prob.(single recombinant v---ct)
0.132 Prob.(single recombinant ct---cv)
0.064 If independent then Prob. (double
recombinant) 0.132 x 0.064 0.0084 expected
number of doubles 1448 x 0.0084 12
Double Cross Overs Expected 12 Observed
8 Explanation a crossover in one region reduces
the probability of a second crossover in an
adjacent region Interference
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Interference (I) 1. Coefficient of coincidence
(C) Obs double recombinants C Exp
double recombinants 2. Interference I 1 -
C 1 - (8 /12) 0.34 I 1 interference
complete I 0 no interference
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If the number of recombinant chromosomes is
half the total, then each of the parental and
recombinant chromosomes will be 1/4 of the total,
and will thus be in a ratio of 1111 Genes
that are 50 cM apart on the chromosome appear to
assort independently
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Genetic map
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• Genes reside in loci on chromosomes
• Genes on different chromosomes assort
  independently, but genes on the same chromosome
  often are inherited together.
• Crossing over at meiosis I can result in the
  separation of alleles that were on the same
  (moms or dads) chromosome.
• The genetic distance between loci is measured by
  the recombination frequency.
• Genes that are more distant tend to be separated
  by crossing over more often.
• Linkage maps show the order of loci, but real
  distances differ because some parts of the
  chromosome are more likely to break.

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In Drosophila, chromosomes in the salivary gland
replicate multiple times without cell division,
forming large structures called polytene
chromosomes. These chromosomes are visible
with a light microscope, so it is possible to
note the regions that have been deleted.
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Deletions (deficiencies) can be observed in
polytene chromosomes.
Ansa da delezione eterozigote
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• Deletion mapping can indicate the physical
  location of a gene on the chromosome, because
  deletion of the dominant allele in a heterozygote
  results in the recessive phenotype.
• a. Expression of the recessive trait caused by
  the absence of a dominant allele is called
  pseudodominance.
• b. Demerec and Hoover (1936) studied a fly strain
  heterozygous for the X-linked recessive mutations
  y, ac and sc (Figure 21.3).

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i. Genetic analysis shows the 3 loci linked at
the left end of the X chromosome. ii. Deletion
experiments correlate the deleted segment with
loss of dominant alleles and the appearance of
pseudodominance. iii. This technique was used
to produce the detailed physical map of
Drosophila polytene chromosomes.
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Different kinds of chromosome maps The genetic
map is an arrangement of genes on a chromosome
that is based on their linkage relationships
The cytological map is the arrangement of genes
with respect to the morphology of
the chromosomes The physical map is the
arrangement of genes as revealed by DNA
sequence The maps are colinear but not
proportional
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Term review