BIOL0003 Lecture 05 Script
BIOL0003 Lecture 05 Script
I will let you into a secret; the genes are on the chromosomes. Now, of course
inference of deep biological truth by clever thinking rather than brute force!
Mendel - no concern with physical nature of the gene: simply a particle, with no
question: where are the genes? Chromosome theory surprisingly contentious for
a long time. Largely because chromosomes visible for only a small part of the
cell cycle (will not discuss in detail here: assume everyone has heard of mitosis
and meiosis).
be dissolved. Also, even in the early history of genetics, became obvious that
there are far more genes than there are chromosomes – can they be the same
thing? What is evidence that genes are held on chromosomes, and what is
implication of this?
fertilisation.
appearance, suggesting that genes were associated with chromosomes. All very
To Mendel made no difference which is the male and which the female parent:
pollen from green with egg from yellow pea gives same result as pollen from
However, Thomas Hunt Morgan, fly lab, Columbia University, around 1916.
Some reciprocal crosses in Drosophila gave very different results. Mutant turned
Crosses gave very different result, depending on which parent was red and
which white.
2) Red male x white female - F1 All females red, all males white!
Mate the F1 flies together; another odd result.
Cross 1) F2 All females red, half males red and half white.
Cross 2) F2 Half females red, half females white, half males red, half males
white.
At first sight, baffling. But - male and female Drosophila differ in one
Males - a large X and a much smaller Y, XY (ie half sperm are X and half are Y).
Hypothesis: the locus for eye colour is carried on the X. Females have two alleles
Male Male
w
X Y X Y
w
X XX XY X XX XY
Female w --------> w w w
X XX XY X XX X Y
Cross 2) would be
Male Male
w
X Y YX
w w w w
X XX X Y X XX XY
Female w w W --------> w w w w
X XX X Y X XX XY
In other words, the pattern of inheritance of the white allele - until then a
object. Strong evidence that genes are indeed borne on chromosomes. Now -
chromosomes.
Soon, a definite proof. Morgan and one of his students noticed that, in some
crosses, the above pattern did not apply. Nearly always, white females with red
males give all daughters red and all sons white in the F1, as in cross 2.
Bafflingly, though, in a few cases, there was the opposite results: white females
mated with red males gave all daughters WHITE, all sons RED! Morgan:
they produce eggs which are XX or have no sex chromosomes at all (Normal
females of course just produce eggs with one X). The cross is then:
XY
w w ww ww
XX XXX XXY
DIES WHITE FEMALE
O XO YO
RED DIES
MALE
humans: XO and XXX humans are viable and female, XXY are viable and male.
male, XO a female. The two systems are less similar than they seem].
The final confirmation: a white-eyed stock arose in which the females have their
ATTACHED-X stock). They ALWAYS gave this anomalous result: that is, when
crossed to red males, they gave white daughters and red sons. Their attached X
chromosomes are transmitted as one unit, and so too are their two copies of the
white allele. A clear proof that the gene for white eye (whose existence has been
Now know many characters in both Drosophila and humans that show X-linked
Sex-linked Inheritance
females, manifest mainly in males. This is because males need only one copy of
the allele (they are hemizygous) to show its effects; females need two.
Also, for affected male, none of his sons are affected, but all his daughters are
carriers. Means that half his grandsons are affected. None of his sons pass on
Blood clotting disorder (in fact several different kinds). Blood in joints,
extravasated blood. Famous case - descendants of Queen Victoria: her 8th child,
Leopold, affected with the disease. Two of her daughters must have been
son, Tsar Alexis severely affected. Others - got into Spanish royal family through
Victoria Eugenie, Ena. Ironic, as she was chosen to infuse new blood into the
Bourbon line: Philip V, unbalanced, sensual; Ferdinand IV - mad and impotent;
Ironic that harmful gene brought in from the mother’s side of the family.
Notable that no history of the disease in British Royal Family before Victoria
chloroform in childbirth, as “robs God of the deep earnest cries which arise in
times of trouble for help”. Now know, though, that it was due to mutation - almost
certainly in the august testicles of Edward, Duke of Kent, her father. Will return
to this later.
Certainly not in present British royal family, as descends through male line from
Now - treatment with factor VIII cures symptoms; notable - this another eg where
mutilation.
One obvious problem with X-linkage: if males manage with one copy of a gene,
how do females cope with two (or, to put it the other way, if females have two,
how can males manage with only one?). We know that usually an extra
chromosome is very harmful and a missing one is lethal. Why does not one sex
discovered it.
switched off: visible as a dark-staining blob in every cell (the Barr Body).
The number of Barr Bodies is always one less than the number of X
some with one and some with the other X chromosome active. If she is a
heterozygote, different patches of cell have one or the other allele expressed.
Every patch is a clone descending from an early embryonic cell, with one or other
of the Xs inactivated. Often refer to Xm - the X of maternal origin - and Xp, the X
of paternal origin.
vision (can separate red from green). However, if sweep laser across retina,
switching from red to green, and asking colour, there are patches of cells that are
colour blind, and patches that are not. Ie mosaic nature of retina. Often quite
homozygotes (one copy of the gene from mother, one from father - but DMD
dystrophy genes in their own cells – usually this has no discernible effect; ie in
effect the MD allele is recessive. However, in some cases, the inactivation takes
place early in development, and many of her cells may have the MD allele active,
with some features of the disease (ie in effect a case of incomplete dominance.
One remarkable case - two girl identical twins, one with DMD, one without.
Turned out that both were heterozygotes, but in one, early in development, the X
with the DMD gene on it had been activated, reaching many of her muscle cells,
while in the other, the alternative X, with the normal allele, was active.
switching off genes near it. In fact, those a long way away may not be fully
inactivation centre on the ACTIVE X. As far as we can see, which one is activa
Notable that Drosophila does the same thing with sex-linked genes to ensure
equality of action in males and females but in a totally different way. Instead of
on, but those of males are set at an activity twice that of females. Quite a
different gene involved - sex-lethal: different alleles kill either males or females,
insight into the location of the genes, on chromosomes. Will pursue this in the
HUMAN CHROMOSOMES
CELL CYCLE
MITOSIS
MORGAN’S LAB
MORGAN’S CROSS
X CHROMOSOME
CLOTTING CASCADE
FACTOR VIII
HAEMOPHILIA – LEAKAGE
VICTORIA FAMILY
HAEMOPHILIA PEDIGREE
CLOSE UP ON RUSSIAN BRANCH
ALEXIS
RASPUTIN
LESCH NYHAN
ISHIHARA TEST
RESULT REVEALED
BARR BODY
MARY LYON
CONES IN EYE
DYSTROPHIN
MD SYMPTOMS