Transcript Pisum

Brilliant in Brünn, part II
“With Pisum it was shown by experiment that the hybrids form egg and pollen cells of
different kinds, and that herein lies the reason of the variability of their offspring.
If it chance that an egg cell unites with a dissimilar pollen cell, we must then assume that
between those elements of both cells, which determine opposite characters some
sort of compromise is effected. The resulting compound cell becomes the foundation
of the hybrid organism the development of which necessarily follows a different
scheme from that obtaining in each of the two original species.
With regard to those hybrids whose progeny is variable we may perhaps assume that
between the differentiating elements of the egg and pollen cells there also occurs a
compromise, in so far that the formation of a cell as the foundation of the hybrid
becomes possible; but, nevertheless, the arrangement between the conflicting
elements is only temporary and does not endure throughout the life of the
hybrid plant. Since in the habit of the plant no changes are perceptible during
the whole period of vegetation, we must further assume that it is only possible
for the differentiating elements to liberate themselves from the enforced union
when the fertilizing cells are developed. In the formation of these cells all existing
elements participate in an entirely free and equal arrangement, by which it is only the
differentiating ones which mutually separate themselves. In this way the production
would be rendered possible of as many sorts of egg and pollen cells as there are
combinations possible of the formative elements.”
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“Brilliant” isn’t strong enough
This is “swish central”
Nothing but net.
Mendel’s data showed – to him – that in a heterozygote,
the two alleles – A and a – remain DISTINCT and
SEPARATE.
They reach a compromise for the life of the plant, but then,
during gametogenesis, they go their separate ways,
unchanged.
To describe this incredibly simple idea as influential would
be akin to calling Michael Jordan a “pretty good shooting
guard.”
Sadly, this idea sat on the bench for the entire 1865-1900
season. More on why that happened – shortly.
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Charles Darwin (1859)
The Origin of Species by Means of Natural Selection
1.
2.
3.
4.
Living organisms multiply; resources
are limited.
Organisms vary. Some variation
affects survival and reproduction.
Like begets like.
Populations of organisms will evolve:
those organisms with characteristics
most favourable for survival and
reproduction will not only have more
offspring, but will pass their
characteristics onto those offspring.
 the characteristics seen in the population will change
heritable change in animals  selection by environment  adaptation to environment
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The problem with step 2
“What was missing from Darwin’s theory was a
source for the variations on which natural
selection acted.
… Darwin addressed the problem of heredity.
He believed that smalled units, which he
called gemmules, were produced by the
cells, and them migrated through the body,
and some of them would be retained in the
… gonads.” EA Carlson, Mendel’s Legacy
“The most unfortunate of the assumptions
underlying Darwin’s mechanism of evolution
was that of blending heredity; i.e., that
parental differences are merged in the
offspring of bisexual reproduction so that
variation is constantly being diminished. The
basis for this assumption wsa the so-called
intermediacy of hybrids which Koelreuter
regarded as a law for all “true” hybrids.”
R. Olby Origins of Mendelism
Copyright © 2006
by Sidney Harris
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Sergei Chetverikov (1926)
On certain aspects of the evolutionary process
from the standpoint of modern genetics
“mutational load”
1. Trap 239 Drosophila
melanogaster near
Moscow.
2. Self their offspring
(brother-sister).
3. 32 recessive loci (=186
in humans).
“… A species, like a sponge,
soaks up heterozygous
mutations, while
remaining phenotypically
homozygous.”
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Archibald Garrod (1902)
Higher frequency of children with alkaptonuria
(urine turns dark on standing and alkalinization)
from consanguineous marriages.
Why?
“There is no reason to suppose that mere
consanguinity of parents can originate such a
condition as alkaptonuria in their offspring, and we
must rather seek an explanation in some
peculiarity of the parents, which may remain latent
for generations…”
http://www.esp.org/foundations/genetics/classical/ag-02.pdf
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Ah!
“It has recently been pointed out by Bateson
that the law of heredity discovered by
Mendel offers a reasonable account of such
phenomena. …”
Garrod (1902) Lancet 2: 116.
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Garrod (1902) Lancet 2: 116.
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A useful term
If a trait follows in its inheritance Mendel’s
first law, that phenomenon is described as
“simple Mendelian inheritance” (SMI).
Examples: cystic fibrosis; sickle cell anemia;
hemophilia A.
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An awful, awful term:
“monogenic trait”
If a trait follows SMI – what does that say
about its genetic architecture?
A highly pernicious school of lack of thought
in biological instruction uses the term
“monogenic trait.” It is most unfortunate.
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X
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In what sense is blood clotting a
“monogenic” trait?
In no sense at all.
What is “simple” is the GENETIC difference between an unaffected
individual and an individual who has hemophilia. It can be as small
as a single base pair change.
In other words, what the phenotype tracking allows us to do is look at
the genetics of the difference.
If a particular phenotype follows SMI, then all that says is:
The difference in genotype between an organism with that phenotype
and without it is due to a genetic difference at a single position in the
genome (=“a single locus”).
Nothing can be learned from this analysis about the number of genes
that are required for that phenotype to develop, or about the role this
particular gene plays in having this phenotype develop.
PKU, for example, has to do with the breakdown of aromatic amino
acids, and its lack causes mental retardation. What is the specific
role of phenylalanine breakdown in cognition?
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Manhood – a monogenic trait
Note: SRY directly causes the conversion of a female embryo to a male one
XY
XX+Sry transgene
Koopman et al. (1991) Nature 351: 117.
Prof. Cline – lecture 25
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Motherhood – a monogenic trait?!
A Defect in Nurturing in Mice Lacking the
Immediate Early Gene fosB
Brown et al.
Cell, Vol. 86, 297–309, July, 1996
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In other words
“Mendelian inheritance” of traits (note: OF TRAITS) is largely the exception,
not the rule in Nature.
Mendel made two titanic contributions to science:
1.
From an epistemological perspective, he created a fundamentally novel,
enormously powerful experimental paradigm, one that replaces all
previous heuristic, trial-and-error-based efforts in this field with a
methodical, hypothesis-driven, rigorous quantitation-based approach, in
which one sets up controlled crosses, determines the number of
phenotypic classes that results from those crosses, analyses their
incidence in each generation separately, and determines the ratios of
organisms that fall into each class. This – to the letter – remains the core
of the ENTIRE genetic research paradigm to this day. It is astonishingly
powerful, as you shall see.
2.
From an ontological perspective, he discovered two of the three most
important principles of the behavior of genes (the equal segregation into
gametes of two alleles of a gene during gametogenesis; and the
independent behavior that two distinct genes exhibit in this process). The
third – linkage – was discovered in 1906 by Bateson and Punnett, and we
will discuss it at great length on Friday. All autosomal genes obey
Mendel’s first law, and all unlinked genes obey Mendel’s second law.
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“What are the genes? What is the nature of the
elements of heredity that Mendel postulated as
purely theoretical units? … Frankly, these are
questions with which the working geneticist has
not much concern himself…
If the gene is a material unit, it is a piece of a
chromosome; if it is a fictitious unit, it must be
referred to a definite location in a chromosome.
… Therefore, it makes no difference in the actual
work in genetics which point of view is taken.”
T.H. Morgan
The Relation of Genetics
to Physiology and Medicine
Nobel Lecture, June 4, 1934
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“The offspring of hybrids in which
several differing traits are associated”
“In the experiments above described plants
were used which differed only on one
essential character. The next task
consisted in ascertaining whether the law
of development discovered in these
applied to each pair of differentiating
characters when several diverse
characters are united in the hybrid by
crossing.”  dihybrid cross
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“Two experiments were made with a considerable
number of plants. In the first experiment the
parental plants differed in the form of the seed
and in the color of the albumen; in the second in
the form of the seed, in the color of the albumen,
and in the color of the seed-coats. Experiments
with seed characters give the result in the
simplest and most certain way.
In order to facilitate study of the data in these
experiments, the different characters of the seed
plant will be indicated by A, B, C, those of the
pollen plant by a, b, c, and the hybrid forms of
the characters by Aa, Bb, and Cc.”
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Ta-daaa! The second law
“There is therefore no doubt that
for all of the traits involved in the
experiments this statement is
valid: the offspring of the hybrids
in which several essentially
different characters are combined
exhibit the terms of a series of
combinations, in which the
developmental series for each
pair of differentiating traits are
combined.
It is demonstrated at the same
time that the relation of each pair
of different traits in hybrid union is
independent of the other
differences in the two parental
plants.”
“Es unterliegt daher keinem
Zweifel, dass für sämmtliche in
die Versuche aufgenommenen
Merkmale der Satz Giltigkeit
habe: die Nachkommen der
Hybriden, in welchen mehrere
wesentlich verschiedene
Merkmale vereinigt sind, stellen
die Glieder einer
Combinationsreihe vor, in
welchen die Entwicklungsreihen
für je zwei differirende Merkmale
verbunden sind.
Damit ist zugleich erwiesen, dass
das Verhalten je zweier
differirender Merkmale in Hybrider
Verbindung unabhängig ist von
den anderweitigen Unterschieden
an den beiden Stammpflanzen.”
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Fig. 4.17
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Narrow-sense heritability (prof. Brem, lecture 31)
Additive vs. dominance vs. interaction genetic variance.
Why Mendel’s second law makes the first one of those so important.
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Gasp #2
“Even the validity of the law formulated for
Pisum requires still to be confirmed, and a
repetition of the more important
experiments is therefore desirable … In
the meantime we may assume that no
basic difference could exist in important
matters, since unity in the
developmental plant of organic life is
beyond question.”
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Gasp #2 continued
“Indessen dürfte man vermuthen, dass in wichtigen
Puncten eine principielle Verschiedenheit nicht
vorkommen könne, da die Einheit im
Entwicklungsplane des organischen Lebens ausser
Frage steht.”
This statement brings and “prescient” to new shades of
meaning. Mendel – a peasant’s son who failed to
graduate from college, working alone in a monastery –
says here that he believes to have discovered a general
law of life, because he thinks that the same core
principles underlie the functioning of all living
beings.
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Gregor Mendel to Carl Nägeli,
Dec. 31, 1866
“Highly esteemed Sir:
The acknowledged preeminence your Honor
enjoys in the detection and classification of
wild-growing plant hybrids makes it my
agreeable duty to submit for your kind
consideration the description of some
experiments in artificial fertilization.”
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Gregor Mendel to Carl Nägeli,
Dec. 31, 1866
“I am not surprised to hear your honor speak of my
experiments with mistrustful caution. … I knew
that the results I obtained were not easily
compatible with our contemporary scientific
knowledge, and that under the circumstances
publication of one such isolated experiment was
doubly dangerous; dangerous for the
experimenter and for the cause he represented.
Thus I made every effort to verity, with other
plants, the results obtained with Pisum.”
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Apomixis
“In botany, apomixis is asexual
reproduction, without fertilization
and modified meiosis.The
modified meiosis yields seeds that
are genetically identical to the one
of the parental plants.”
In zoology, the cognate
phenomenon is known as
parthenogenesis.
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