Download HEREDITY - Susquehanna University

HEREDITY
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Early Explanations for Heredity
Genes and Chromosomes
Structure of DNA
Central Dogma of Molecular Biology
PCR and Genome Sequencing
Preformation
• Pre-existing
• All people who will be born
have been formed
• The homunculus unfolds to
form the adult
• Came from Egyptian
alchemy
Epigenesis
• Assembled
• Each person is put together
by contributions of each
parent
• The adult develops from an
amorphous mass
• Came from Pythagoras and
Aristotle
Preformation
• More in line with
western Christianity
• Leeuwenhoek and
other early
microscopists
claimed to have seen
the homunculus
Epigenesis
• Later microscopists noted
that certain tissues, like the
apical meristems of plants,
were made of a region of
identical cells that
developed into typical plant
tissues.
• William Harvey (15781657, England) stated that
all animals came from eggs
and they were fertilized by
transference of hereditary
material from the semen.
Pangenesis
• Charles Robert Darwin (18091882, Britain)
• Hereditary particles from all
parts of the body are
transported by the circulatory
system and concentrated in the
gametes.
• It began to take on a Lamarkian
perspective and explain
evolution by acquired characters
• Attempted to be confirmed by
Francis Galton (1822-1911,
Britain). Disproved
Germ Plasm Theory
• Friedrich Leopold
August Weismann
(1834-1914, Germany)
• Hereditary particles
retained only if needed
as development
progresses in somatic
cells, but remains
unchanged in germ
plasm ~disproved by
cloning.
Hugo de Vries
• 1848-1936, Netherlands
• Modified pangenesis
• Called particles pangenes
(shortened to genes later)
• Working on Evening Primrose
noticed flower color either
white or yellow in particular
ratios
• Developed mutation theory of
evolution
• In 1900 discovered papers
published 30 years earlier by
Gregor Johann Mendel
• Also discovered by Carl
Correns (1864-1933,
Germany) and Erich von
Tschermak (1871-1962,
Austria)
Gregor Johann Mendel
• 1822-1884, Austrian Empire (now
Czech Republic)
• Joined Augustinian Order and
took name Gregor
• Studied physics under Doppler
• Failed teaching exam (oral
portion) and became an
administrator of monastery of
Brünn (Brno in Czech)
• Became interested in heredity
and began to study mice but
abbot uncomfortable having a
monk who studied sex; so,
Mendel began to study peas and
looked at 7 traits that seemed to
be independent of each other.
• Communicated with Carl Wilhelm von
Nägeli (1817-1891, Switzerland).
• Theory of ideoplasm (a portion of the
cytoplasm that carried hereditary
information)
• Commented to Mendel: ‘your paper is
of some interest but is too empirical to
be important to the science of
heredity’.
• Advised him to work on animals
instead
Law of Segregation
Dominant and recessive
phenotypes.
(1) Parental generation.
(2) F1 generation.
(3) F2 generation.
Dominant (red) and
recessive (white)
phenotype look alike in
the F1 (first) generation
and show a 3:1 ratio in
the F2 (second)
generation.
Law of Independent Assortment
Dihybrid cross. The phenotypes of
two independent traits show a
9:3:3:1 ratio in the F2generation. In
this example, coat color is indicated
by B(brown, dominant) or b (white),
while tail length is indicated
by S (short, dominant) or s (long).
When parents are homozygous for
each trait (SSbb andssBB), their
children in the F1 generation are
heterozygous at both loci and only
show the dominant phenotypes. If
the children mate with each other, in
the F2 generation all combinations of
coat color and tail length occur: 9 are
brown/short (purple boxes), 3 are
white/short (pink boxes), 3 are
brown/long (blue boxes) and 1 is
white/long (green box).
Genes and Chromosomes
• Walter Stanborough Sutton
(1877-1916, USA)
• Noted that the segregation and
independent assortment of
grasshopper chromosomes
during meiosis conformed to
Mendel’s Laws (1900-1903)
• Thus Genes must be located on
the chromosomes
• Theodor Heinrich Boveri (18621915, Germany) independently
came to the same conclusion
Chromosomes and Fruit Flies
• T. H. (Thomas Hunt) Morgan (1966-1945,
USA)
• Began to study mutations in fruit flies after
rediscovery of Mendel’s Laws
• Sought out mutant forms
• Discovered sex-linked traits and began to map
chromosomes by cross-over distance
Mutations and Fruit Flies
• H. J. (Hermann
Joseph) Muller (18901967, USA, USSR,
Britain)
• Followed Morgan and
worked on fruit flies
• Induced mutations by
high temperature, Xrays
What is the gene made of?
• Oswald Theodore Avery (1877-1955,
Canada, USA)
• Showed that DNA moved from one
bacterium to another could transform a
benign strain to a virulent strain in 1940s
Hershey and Chase (1952)
Alfred Day Hershey (1908-1997,
USA) and Martha Cowles Chase
(1927-2003, USA)
Structure of DNA (1953)
• James Dewey Watson (1928-, USA)
• Francis Harry Compton Crick (1916-2004, Britain
& USA
• Maurice Hugh Frederick Wilkins (1916-2004,
New Zealand & Britain)
• Rosalind Elsie Franklin (1920-1958, Britain)
Central Dogma of Molecular Biology
• Francis Crick (1958)
• Sequence of
information transfer
Decoding DNA
• Marshall Warren Nirenberg
(1927-2010, USA)
• Began to perform simple
(conceptually) experiments
to generate polypeptides by
using RNA sequences of
– UUU… (generated poly
phenylalanine)
– AAA…(generated poly lysine)
– CCC…(generated poly
proline)
The Codon
George Gamow proposed that 3 bases would serve to
unambiguously code for the 20+ different amino acids to
code for particular polypeptides
HIV and Reverse Transcriptase
Polymerase Chain Reaction
Developed in 1983 by Kary Banks Mullis (1944, USA)
Genome Sequencing
• John Craig Venter (1946, USA)
• Employed shotgun method to
sequence DNA with private
company in competition with the
Human Genome Project
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Long chains broken randomly
Small pieces sequenced
Then small sequences reassembled
Method brought Human Genome
Project in years ahead of schedule
and billions under budget.
• Known recently for creating
artificial life with assembled
genome.
Whole Genome Shotgun Sequencing
Hierarchical Shotgun Sequencing
Human Genome Project
• James Watson was the first director
(1988-1992)
• Human genome has ~20,500 genes
• International effort begun in 1980s using
PCR
• Strong effort begun in 1990
• Separate genome into pieces
~150,000bp and sequence
• Look for start/stop codes
• 1st draft published 2000
• Completed genome 2003
• By 2009, a personal genome could be
completed for less than $2,000