Transcript Core Concepts in Genetics - University of Colorado Boulder

Core Concepts in
Genetics
Mendelian Inheritance
The Double Helix
Origin of Mendelian
Genetics
 "In 1859 I obtained a very fertile
descendant with large, tasty seeds
from a first generation hybrid. Since
in the following year, its progeny
retained the desirable characteristics
and were uniform, the variety was
cultivated in our vegetable garden,
and many plants were raised every
year up to 1865."
(Gregor Mendel to Carl Nägeli,
April 1867, from Mendel [1950])
Knowledge at the time
 Hybridization was a familiar
term at the time in plant work.
(Kölreuter, Gärtner, Herbert,
Lecoq, Wichura)
 However, amongst the
numerous plant hybrid
researchers there was no law or
methodology that described the
formation of hybrids.
 Hence, Mendel sought to design
detailed experiments to describe
these phenomena – The Law of
Combination.
Mendel’s Hypotheses
 Mendel perceived his
experiments as a means to
explaining the evolution of
organic forms of life.
 Mendel conceptualized that
“something” had to be
transmitted across the
generations of an organism that
allowed observable
characteristics to persist.
Mendel’s Design
Characteristics of Subjects
1. Possess constant differentiating
characteristics (a.k.a True
Breeding).
2. The hybrids of such plants must,
during the flowering period, be
protected from the influence of all
foreign pollen, or be easily capable
of such protection.
3. The hybrids and their offspring
should suffer no marked
disturbance in their fertility in the
successive generations
Mendel’s Design
After numerous trials with several
members of the Leguminosae
family the genus Pisum was found
to possess all the afore mentioned
characteristics.
The Monohybrid Cross
 By examining hybrids created
by a pair of true breeding plants
that differed on a single
characteristic Mendel sought “to
deduce the law according to
which they appear in successive
generations”.
 P1(round seed) x P2 (wrinkled)
= F1 (all round seed)
Observations of the
Monohybrid Cross (F1)
 All the hybrid plants formed
had the characteristics of a
single parent.
 Mendel concluded that the
characteristics that persisted,
unaltered after transmission
were dominant, and those
which became latent/obscured
were recessive.
 Reciprocal crosses indicated
that dominant/recessive
characters were not affected by
the nature of the parent.
Observations of the
Monohybrid Cross (F2)
 Mendel then proceeded to self-
pollinate all of the progeny of
the F1 generation.
 F1 (round) x F1 (round)
= F2 ( ¾ round : ¼ wrinkled)
 Progeny of the F2 generation
always presented themselves
with dominant and recessive
characteristics.
 The Monohybrid Cross
Observations of the
Monohybrid Cross
Backcross
 Curious of the results Mendel
conducted test crosses to
determine the properties of F2
progeny.
 Backcross – F2 x P2 (recessive)
 Backcross results indicate that
of the ¾ round seeds 1/3
produce only round seeds and
2/3 produce round and wrinkled
seeds.
 The Test Cross
Conclusions of the
Monohybrid Cross (P1-F2)
 For every characteristic
examined the ratio of the
offspring of the F1 generation is
fairly constant.
 F1 hybrid is a heterozygote
 P1 & P2 are homozygotes.
Conclusions of the
Monohybrid Cross (P1-F2)
 If A represents the dominant
characteristic and a the
recessive, then the expression:
A + 2Aa + a, describes the ratio
of the parental forms to the
hybrid forms in the F2
generation.
 Furthermore, Hybrids display a
natural tendency to revert back
to their parental forms.
 However, do not entirely
disappear.
The Dihybrid Cross
 Mendel then proceeded to
combine plants that varied by
two characteristics.
 His F1 hybrid results were
similar to that of the
monohybrid crosses.
 His F2 results consistently
occurred in a ratio of 9:3:3:1
which consisted of the two
parental forms and two hybrid
forms.
 The Dihybrid Cross
Reproductive Cells of
Hybrids
 To complete his theory on the
inheritance of characteristics
Mendel’s last set of experiments
demonstrated that the egg cells
of the plants were the vector for
the transmission of information
across generations.
Mendel’s Law of
Combination
 The law of combination of
different characters which
governs the development of the
hybrids finds therefore its
foundation and explanation in
the principle enunciated, that
the hybrids produce egg cells
and pollen cells which in equal
numbers represent all constant
forms which result from the
combinations of the characters
brought together in fertilization.
Culmination of Mendel’s
Work
The Law of Segregation
There are two elements of
heredity for each trait in each
individual that segregate during
reproduction. Offspring receive
one of the two elements from each
parent. Furthermore, one of these
elements may dominate the other.
Culmination of Mendel’s
Work
The Law of Independent
Assortment
Based upon the constant results of
dihybrid crosses the elements for
one characteristic assort
independent from the elements for
another characteristic.
The Double Helix
The Complementary
Model
J.D. Watson
F.H. Crick
Evidence for Fibrous
Nature of DNA: Physicochemical analysis
 DNA is a long
asymmetrical chain
that consists of a 5carbon sugar and
phosphate backbone
joined in a 3`-5`
direction by
phosphodisester
bonds.
 Each sugar has 1 of 4
bases attached to it
Adenine, Guanine,
Cytosine, and
Thymine.
DNA Has Two Chemical
Chains: X-ray
Crystallography
 Two alternating
forms of DNA
exists.
 A crystalline form
that occurs at 75%
humidity (top) with
a 2.8 A reflexion
about its meridian..
 A para-crystalline
form that occurs at
higher humidity
(bottom) with 3.4 A
reflexion about its
meridian.
 Density data
indicate possibly
two distinct
polynucleotide
chains
Hypothesized Structure
 DNA is three




dimensional.
DNA has two chains
that are coiled
around a single axis
and held together by
hydrogen bonds.
Both chains follow
right handed helices.
The phosphates and
sugar groups are on
the outside and the
bases on the inside.
A repeat distance of
34A with a reflexion
of spacing 3.4A.
Hypothesized Structure
 The two chains are
held together by
hydrogen bonds
between the bases.
 The base pairing is
specific.
 Adenine-Thymine
Guanine-Cytosine
 Each chain
complements the
other because of the
specific base pairing.
Evidence supporting the
Complementary Model
X-ray pictures suggests that:
 DNA’s basic structure is helical.
 High concentration of atoms on
the circumference of the helix.
 The polynucleotide chains are
not distinct from each other.
Evidence supporting the
Complementary Model
Titration curves of DNA suggest:
 Hydrogen bond formation is
characteristic of DNA structure
Analytical data of the bases
suggests:
 The amount of A – T and C – G
is very close.
Characteristics of
Genetic Material
1. Must be able to self-
replicate.
2. Must exert a highly specific
influence on the cell.
DNA Replication: The
Complementary Model
 Of the two characteristics
Watson & Crick proposed only
a practical mechanism for
replication.
 Complementary base pairing is
the backbone of replication.
 But how does the interior of the
helix allow itself to be
replicated?
DNA Replication: The
Complementary Model
 Proposed that DNA unwinds by
breaking the hydrogen bonds
between the strands.
 The single strands would then
serve as a template to which
complementary free nucleotides
would attach and form 2 helices
where there was originally one.
 They were unaware of the
numerous protein machinery
(helicase, ligase, polymerases,
etc.) that facilitated this process.
DNA Replication Today
DNA replication