HEREDITY Early Explanations for Heredity Genes and Chromosomes

HEREDITY

• • • Early Explanations for Heredity Genes and Chromosomes Structure of DNA Central Dogma of Molecular Biology PCR and Genome Sequencing

Preformation Epigenesis • Pre-existing • All people who will be born have been formed • The homunculus unfolds to form the adult • Came from Egyptian alchemy • 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) 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.

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 andss. BB), 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).

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 1940 s

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

Using the Central Dogma to make a vaccine

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 – – 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

Current method for Human Genome Sequencing • Separate genome into pieces ~150, 000 bp and sequence • Look for start/stop codes to define genes • Reassemble the genome in a computer using the reference sequence Image from NIH

Human Genome Project • • James Watson was the first director (1988 -1992) Human genome has ~20, 500 genes International effort begun in 1980 s using PCR Strong effort begun in 1990 1 st draft published 2000 Completed genome 2003 By 2009, a personal genome could be completed for less than $10, 000 By 2020, a personal genome could be completed for less than $1, 000