Early Explanations for Heredity Genes and Chromosomes Structure
of DNA Central Dogma of Molecular Biology PCR and Genome
Sequencing
Slide 3
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
Slide 4
Preformation More in line with western Christianity Leeuwenhoek
and other early microscopists claimed to have seen the
homunculus
Slide 5
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
(1578- 1657, England) stated that all animals came from eggs and
they were fertilized by transference of hereditary material from
the semen.
Slide 6
Pangenesis Charles Robert Darwin (1809- 1882, 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
Slide 7
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.
Slide 8
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)
Slide 9
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 Brnn (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.
Slide 10
Communicated with Carl Wilhelm von Ngeli (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
Slide 11
Law of Segregation Dominant and recessive phenotypes. (1)
Parental generation. (2) F 1 generation. (3) F 2 generation.
Dominant (red) and recessive (white) phenotype look alike in the F
1 (first) generation and show a 3:1 ratio in the F 2 (second)
generation.
Slide 12
Law of Independent Assortment Dihybrid cross. The phenotypes of
two independent traits show a 9:3:3:1 ratio in the F 2 generation.
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 F 1 generation are heterozygous at both loci
and only show the dominant phenotypes. If the children mate with
each other, in the F 2 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).
Slide 13
Genes and Chromosomes Walter Stanborough Sutton (1877-1916,
USA) Noted that the segregation and independent assortment of
grasshopper chromosomes during meiosis conformed to Mendels Laws
(1900-1903) Thus Genes must be located on the chromosomes Theodor
Heinrich Boveri (1862- 1915, Germany) independently came to the
same conclusion
Slide 14
Chromosomes and Fruit Flies T. H. (Thomas Hunt) Morgan
(1966-1945, USA) Began to study mutations in fruit flies after
rediscovery of Mendels Laws Sought out mutant forms Discovered
sex-linked traits and began to map chromosomes by cross-over
distance
Slide 15
Mutations and Fruit Flies H. J. (Hermann Joseph) Muller (1890-
1967, USA, USSR, Britain) Followed Morgan and worked on fruit flies
Induced mutations by high temperature, X- rays
Slide 16
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
Slide 17
Hershey and Chase (1952) Alfred Day Hershey (1908-1997, USA)
and Martha Cowles Chase (1927-2003, USA)
Slide 18
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)
Slide 19
Slide 20
Central Dogma of Molecular Biology Francis Crick (1958)
Sequence of information transfer
Slide 21
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)
Slide 22
The Codon George Gamow proposed that 3 bases would serve to
unambiguously code for the 20+ different amino acids to code for
particular polypeptides
Slide 23
HIV and Reverse Transcriptase
Slide 24
Polymerase Chain Reaction Developed in 1983 by Kary Banks
Mullis (1944, USA)
Slide 25
Genome Sequencing John Craig Venter (1946, USA) Employed
shotgun method to sequence DNA with private company in competition
with the Human Genome Project 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
Slide 26
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 1 st draft published 2000 Completed genome 2003 By 2009, a
personal genome could be completed for less than $2,000