HEREDITY

HEREDITY

• 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 (1578-1657, England) stated that all animals came from eggs and they were fertilized by transference of hereditary material from the semen.

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

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 (1862-1915, 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 (1890-1967, USA, USSR, Britain)

• Followed Morgan and worked on fruit flies

• Induced mutations by high temperature, X-rays

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 CodonGeorge 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 ReactionDeveloped 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– 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