Enter the fruit fly
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Thomas Hunt Morgan, the first nativeborn American to win the Nobel Prize,
founder of modern genetics
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Bridges
Sturtevant
Morgan
Muller
Morgan et al. 1915
“As will be shown now, certain factors follow
the distribution of the X chromosome and
are therefore supposed to be contained
in them.”
Emphasis mine – fdu.
↓
Genes lie on chromosomes
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“The supposition that particles of
chromatin, indistinguishable from
each other and indeed almost
homogeneous under any
known test, can by their material
nature confer all the properties of
life surpasses the range of even
the most convinced materialism.”
Bateson, W. (1916) The
mechanism of Mendelian heredity
(a review). Science, 44, 536-543.
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A problem and a solution
“The value and utility of any experiment…”
(Mendel)
“What was needed to open up genetics to new
phenomena was an organism that bred rapidly,
produced lots of progeny, and was inexpensive
to maintain” (Carlson)
“Fruit flies can be raised on a mixture of corn meal,
yeast, sugar, and agar. Flies complete their life
cycle from fertilization to emergence of the adult
fly in 10 days. A female can produce 3,000
progeny in her lifetime. A single male can sire
well over 10,000 offspring.” (Hartwell)
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(aka chr. 1)
Note: no crossing over in male meiosis!
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Morgan and Drosophila
(go Bears)
Morgan was not a geneticist by training (he was an embryologist), and he
was not the first one to use Drosophila for purposes of genetic research
(Castle was).
“One of the baffling problems of breeders in pre-Mendelian days had
been the effects of inbreeding and crossbreeding. What these were was a
much-debated question. We set out to give it an experimental test and
found ready to hand a rapidly breeding little fly, Drosophila, being cultured
in the laboratory by a graduate student as embryological material. This,
he told us, would complete a generation within a fortnight. (Charles
Woodworth, prof entomology at UC Berkeley). … We began culturing the
fly on pulped Concord grapes, but this gave us poor results as many of
the larvae would get drowned and then our population statistics were no
good. As grapes became out of season, we tried other fruits, and finally
hit the jackpot in bananas. …The conclusion drawn [from our studies]
was that inbreeding reduces very slightly the productiveness of
Drosophila. … This was not a conclusion of world-shaking importance.
The important outcome of this investigation was that it called to Morgan’s
attention a new source of material for experimental study not subject to
the limitations of slow-breeding laboratory mammals.” WE Castle (prof
genetics UC Berkeley) The Beginnings of Mendelism in America – in
Genetics in the 20th Century, p. 73.
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Tough early going
“… Morgan had been working
on fruit flies for at least two
years before he found his
most significant mutation, a
white-eyed fly. For this new
approach, Morgan was his
own first student. He bred
the fliles for two years
without assistance. … He
pointed to the shelves with
flies and [said] that he had
wasted two years and had
gotten nothing for his work.”
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“May 1910 was when the revolution
began. Morgan found a white-eyed
male running around in one bottle.”
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One of the best-known opening
passages in the history of the
English language
“It is a truth universally acknowledged that a single man in
possession of a good fortune must be in want of a wife.”
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“The Mechanism of
Mendelian Heredity” (1915)
Thomas Hunt Morgan
Alfred Sturtevant
Hermann Muller
Calvin Bridges
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Nothing special here.
Just like seed color in
peas.
Normal Mendelian
ratio (3:1) – but where
are the white-eyed
females?!!
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Nettie Stevens, discoverer of the
sex chromosomes
Nettie Stevens was one of the first female scientists to make a name for herself in
the biological sciences. She was born in Cavendish, Vermont. Her family
settled in Westford, Vermont. Stevens' father was a carpenter and handyman.
He did well enough to own quite a bit of Westford property, and could afford to
send his children to school.
Stevens was a brilliant student, consistently scoring the highest in her classes. In
1896, Stevens went to California to attend Leland Stanford University. She
graduated with a masters in biology. Her thesis involved a lot of microscopic
work and precise, careful detailing of new species of marine life. This training
was a factor in her success with later investigations of chromosomal behavior.
After Stanford, Stevens went to Bryn Mawr College for more graduate work.
Thomas Hunt Morgan was still teaching at Bryn Mawr, and was one of her
professors. Stevens again did so well that she was awarded a fellowship to
study abroad. She traveled to Europe and spent time in Theodor Boveri's lab
at the Zoological Institute at Wurzburg, Germany. Boveri was working on the
problem of the role of chromosomes in heredity. Stevens likely developed an
interest in the subject from her stay.
In 1903, Stevens got her Ph.D. from Bryn Mawr, and started looking for a
research position. She was eventually given an assistantship by the Carnegie
Institute after glowing recommendations from Thomas Hunt Morgan, Edmund
Wilson and M. Carey Thomas, the president of Bryn Mawr. Her work on sex
determination was published as a Carnegie Institute report in 1905.
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The useful mealworm
“It is perfectly clear that an egg
fertilized by a spermatozoon
containing the smaller
hererochromosome produces a
male, while one fertilized by a
spermatozoon containing the
larger heterochromosome
develops into a female.”
 XO is male and XX is female
(until 1916)
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Edmund Wilson – arguably, the first
XY person on Earth
“In many species of insects there are two
classes of spermatozoa, equal in
number, which in the early stages of their
development, differe visibly in respect to
the nuclear constitution; while there is
but one class of egg. … That is to say, if
the two kinds of spermatozoa be
designated as the X-class and the Yclass, respectively; the eggs are all of
the X-class. The male may accordingly
be designated as the heterogametic sex,
the female as the homogametic.”
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Dr. Thomas Ried, NCI/NIH:
SKY of hormal human cell
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Calvin Bridges
… “raised by his grandparents in upstate New York, both of
his parents dying young. He was a talented student buit
his grandparents were poor and Bridges had to make do
with clothing that was constantly mended. He was too
ashamed to go to social activities in high school because
of his ragged appearance. He received a scholarship to
attend Columbia University, but he had to support
himself with part-time work. Bridges took the same
introductory biology course as Sturtevant, and Morgan,
who learned of Bridges’ circumstances, asked him to be
a part-time bottle-washer and food preparator for the fly
work that was gaining momentum in Morgan’s
laboratory.” Carlson Mendel’s Legacy
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vermilion
“… Bridges’ circumstances changed
approximately a year after he began
working for Morgan. He showed Morgan a
bottle that contained a fly whose eye color
seemed to be brighter than usual. Morgan
isolated the fly, showed that it carried
another X-linked trait, and called that trait
vermilion. He also assigned Bridges to a
desk and told him to look for more
mutations.”
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(A) Bridges (left) and Sturtevant in 1920. (B) Morgan in 1917. The photo of Morgan,
who was camera shy, was taken by Sturtevant using a camera hidden in an incubator
and operated remotely by means of a string. The books and microscope in the
background were at Sturtevant's desk
G. Rubin and E. Lewis Science 287: 2216.
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Criss-cross inheritance: white-eyed
sons and red-eyed daughters of whiteeyed mothers and red-eyed fathers
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The “exceptional
female”
appears
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Fig. 13.28
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How could a white-eyed mother
have a white-eyed daughter?
Note:
An XXY Drosophila is
female.
An XXY human is male.
Y?
Fig. 4.21
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Normal female
White-eyed daughters
of an “exceptional” mother
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Bridges, C. B. 1935. Salivary chromosome maps
with a key to the banding of the chromosomes of
Drosophila melanogaster. J. Hered. 26: 60–64
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Fine, fine, genes are on
chromosomes. Now what?
The next two major advances in genetics both came
from the study of apparent exceptions to Mendel’s
laws.
#1. Strong deviations from a 1:1:1:1 phenotyping ratio
in a AaBb x aabb cross  “coupling and repulsion” 
linkage  genetic map
#2. Highly aberrant phenotypic
ratios (e.g., 9:3:4) when – for
example – brother-sister mating
black Labrador retrievers fathered
by a black Dad and yellow Mom
 epistasis
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