The History of Genetics From classical genetics to the personal human genome

Classical Genetics: Gregor Mendel (1860) Discovered the classical laws of inheritance through his work with pea plants Mendel’s work remained unknown to scientists until the 1900s!

Frederick Miescher (1869) Extracted DNA from cell nuclei Observed that it contained much phosphorus but no sulfur & did not behave like a protein Called it “nuclein”

Modern Genetics Thomas Morgan (1910) Experimented with fruit flies (D. melanogaster), which have large enough chromosomes to be seen with a light microscope Discovered the gene

The 1920s Several groups of scientists together uncovered the chemical makeup of DNA Proposed that is made of 3 groups: deoxyribose sugar, phosphate and nitrogenous base

Frederick Griffith (1928) Experimented with pneumonia bacteria, discovered the genetic link between genes and traits Observed that colonies of bacteria can be transformed from a non-virulent (‘rough’ colonies) to a virulent form (‘smooth’ colonies) with addition of a gene

Hammerling (1930s): experimented on algae to show that hereditary information is found in the nucleus of cells Beadle & Tatum (1941): each gene produces a different enzyme Chargaff (1949): analyzed data from many different organisms to show that in DNA, the ratio of adenine to thymine =1, and the ratio of cytosine to guanine = 1

Hershey & Chase (1952) Used experiments on bacteriophages (viruses) to show that DNA, not protein, is the hereditary material & carries genetic information

Rosalind Franklin (1953) Used X-ray diffraction analysis of DNA crystals to show that DNA is a helix & is about 2nm in diameter

Watson & Crick (1953) Used Franklin’s and Chargaff’s research to discover the structure & build a double-helix model of DNA, for which they received the Nobel Prize in 1962 (shared with Wilkins, a colleague of Franklin’s)

Meselson & Stahl (1958) Found that DNA replication is “semi- conservative” Each DNA molecule is composed of one parent strand and one newly synthesized strand (support for Watson & Crick’s model)

Molecular Genetics Hamilton Smith (1970): Discovery of restriction enzymes (enzymes that cuts DNA at specific sequences) Cohen & Boyer (1970s): pioneered techniques in biotechnology that are now commonplace; i.e. inserting new genes into bacterial plasmids

Molecular Genetics Nestor & Chilton (1981): used plasmids to introduce foreign genes into plant cells (transgenics) Kary Mullis (1987): development of polymerase chain reaction (PCR), a method of copying a small amount of DNA many times for purposes of testing

Mapping the Genome Technology is now a the point where we can map the entire genome of a species The first eukaryotic genome sequenced was that of Saccharomyces cerevisiae (yeast) in 1995 Human Genome Project: mapping of ,000 human genes, completed in 2003

Human Genome Project The human genome project began in 1990, took 13 years and cost over $3 billion dollars to complete. The sequence sample is from a mixture of multiple individuals, though >70% caucasian in origin In order to process all of the data from sequencing, computers in schools, universities, libraries, etc. were ‘borrowed’ at night!

Human Genome Project – Major Findings Humans have about 20,000 protein-coding genes and about 6000 RNA genes in their genome, totaling about 26,000 coding genes This is about the same number as a fly! About half of your DNA appears to do absolutely nothing! More that 1.4 million single-nucleotide polymorphisms (changes in sequence) have been found so far

Looking Forward Scientists hope within the next few years to make personal genome sequences a reality This means that you would be able to know which genetic conditions for which you have a predisposition at any time in your life! What do you think? If you have a predisposition for heart disease or cancer when you get older, would you want to know?

The Personal Genome Era Technology and expertise is approaching the point where: Cost = $1000/genome Time = less than a week, maybe even a day/genome