- Modern Evolution of Genetics Timeline
- 1868 - Austrian monk Gregor Mendel studied the inheritance of traits between generations based on experiments involving garden pea plants. He deduced that there is a certain essence that is passed on between generations from both parents. Mendel established the basic principles of inheritance, namely, the principles of dominance, independent assortment, and segregation.
- 1871 - J. F. Miescher isolated cell nuclei. Miescher separated the nucleic cells from bandages and then treated them with pepsin (which breaks down proteins). From this, he recovered an acidic substance which he called “nuclein.”
- 1889 - Richard Altmann purified protein free DNA. However, the nucleic acid was not as pure as he had assumed. It was determined later to contain a large amount of protein.
- 1902 - Archibald Garrod discovered inborn errors of metabolism. An explanation for epistasis is an important manifestation of Garrod’s research, albeit indirectly. When Garrod studied alkaptonuria, a disorder that makes urine quickly turn black due to the presence of gentesate, he noticed that it was prevalent among populations whose parents were closely related.
- 1902 - Walter Sutton and Theodor Boveri established chromosome theory. Boveri was studying sea urchins and he found that all the chromosomes in the sea urchins had to be present for proper embryonic development to take place. Sutton's work with grasshoppers showed that chromosomes occur in matched pairs of maternal and paternal chromosomes which separate during meiosis and could "may the physical basis of the Mendelian law of heredity."
- 1908 - G.H. Hardy and Wilhelm Weinberg proposed a theorem to describe the frequency of alleles of a gene for a given population. The Hardy Weinberg Equilibrium is a tool used for genetic analysis, which can determine how closely related two individuals are.
- 1910 - Thomas Morgan determined the nature of sex-linked traits by studying Drosophila melanogaster. He determined that the white-eyed mutant was sex-linked based on Mendelian's principles of segregation and independent assortment. More significantly, Morgan and his students affirmed the Chromosome Theory of Heredity.
- 1911 - Alfred Sturtevant, one of Morgan's students, invented the procedure of linkage mapping which is based on the frequency of recombination. A few years later, he constructed the world's first chromosome map.
- 1923 - Frederick Griffith studied bacterial transformation and observed that DNA carries genes responsible for pathogenicity.
- 1933 - Thomas Morgan received the Nobel prize for linkage mapping. His work elucidated the role played by the chromosome in heredity.
- 1941 - George Beadle and Edward Tatum demonstrated that genes encode for enzymes, which induce mutations in neurospora.
- 1944 - Oswald Avery, Colin MacLeod and Maclyn McCarty refined the experiment done by Griffith in 1923. Avery, MacLeod and McCarthy’s experiment on Bacterial transformation and proved that DNA carries genetic information responsible for pathogenicity with the use of Ribonuclease, Protease, as well as Deoxyribonuclease.
- 1950 - Erwin Chargaff determined the pairing method of Nitrogenous bases. Chargaff and his team studied the DNA from multiple organisms and found three things (also known as Chargaff's rules). First, the concentration of the Pyrimidines (thymine and adenine) is always found in the same amount as one another. Second, the concentration of purines (cytosine and guanine) is always the same. Last, Chargaff and his team found the proportion of pyrimidines and purines to be the same.
- 1953 - James Watson and Francis Crick with the contributions of Rosalind Franklin and Maurice Wilkins discovered the double helix structure of DNA. By studying the data from x-ray crystallography work done by Franklin, Watson and Crick were able to predict the double helix structure of the DNA molecule. They also used the data provided by Chargaff, which demonstrated the ratios of purines and pyramidines.
- 1955 - Alexander R. Todd determined the chemical makeup of nitrogenous bases. Todd also successfully synthesized Adenosine Triphosphate (ATP) and Favin Adenine Dinucleotide (FAD) . He was awarded the Nobel prize in Chemistry in 1957 for his contributions in the scientific knowledge of nucleotides and nucleotide co-enzymes.
- 1955 - Joe Hin Tjio determined the number of chromosomes in humans to be of 46. Tjio was attempting to refine an established technique to separate chromosomes onto glass slides by conducting a study of human embryonic lung tissue, when he saw that there were 46 chromosomes rather than 48. This revolutionized the world of cytogenetics.
- 1957 - Arthur Kornberg with Severo Ochoa synthesized DNA in a test tube after discovering the means by which DNA is duplicated . DNA polymerase 1 established requirements for in vitro synthesis of DNA. Kornberg and Ochoa were awarded the Nobel Prize in 1959 for this work.
- 1957/1958 - Robert W. Holley, Marshall Nirenberg, Har Gobind Khorana proposed the nucleotide sequence of the tRNA molecule. Francis Crick had proposed the requirement of some kind of adapter molecule and it was soon identified by Holey, Nirenberg and Khorana. These scientists help explain the link between an messenger RNA nucleotide sequence and a polypeptide sequence. In the experiment, they purified tRNAs from yeast cells and were awarded the Nobel prize in 1968.
- 1961 - Francis Crick and Sydney Brenner discovered frame shift mutations. In the experiment, proflavin-induced mutations of the T4 bacteriophage gene (rIIB) were isolated. Proflavin causes mutations by inserting itself between DNA bases, typically resulting in insertion or deletion of a single base pair. The mutants could not produce functional rIIB protein.
- 1961 - Sydney Brenner, Francois Jacob and Matthew Meselson identified the function of messenger RNA.
- 1966 - Marshall W. Nirenberg, Philip Leder, Har Gobind Khorana cracked the genetic code by using RNA homopolymer and heteropolymer experiments, through which they figured out which triplets of RNA were translated into what amino acids in yeast cells.
- 1970 - Hamilton O. Smith and Daniel Nathans purified the first restriction enzyme (EcoRI). This enzyme is produced by the E-coli strain RY13 and its purpose is to protect the bacteria’s genetic material from invasion by foreign DNA.
- 1972 - Stanley Norman Cohen and Herbert Boyer at UCSF and Stanford University constructed Recombinant DNA which can be formed by using restriction Endonuclease to cleave the DNA and DNA ligase to reattach the “sticky ends” into a bacterial plasmid.
- 1976 - DNA sequencing methodology is devised. Frederick Sanger and Charles Coulson described a method for determining the sequence of DNA using a four lane polyacrylamide gel electrophoresis (PAGE). By interrupting DNA synthesis by exposure to a small concentration of a Dideoxynucleoside Triphosphate (DdNTP), a different banding pattern can be generated for each different base and a different distance can be identified for each base pair on the gel. This technique is called the Sanger Coulson Technique.
- 1980 - Paul Berg, Walter Gilbert and Frederick Sanger developed methods of mapping the structure of DNA. In 1972, recombinant DNA molecules were produced in Paul Berg’s Stanford University laboratory. Berg was awarded the 1980 Nobel Prize in Chemistry for constructing recombinant DNA molecules that contained phage lambda genes inserted into the small circular DNA mol.
- 1980 - Stanley Norman Cohen and Herbert Boyer received first U.S. patent for gene cloning, by proving the successful outcome of cloning a Plasmid and expressing a foreign gene in bacteria to produce a “protein foreign to a unicellular organism." These two scientist were able to replicate proteins such as HGH, Erythropoietin and Insulin. The patent earned about $300 million in licensing royalties for Stanford.
- 1982 - FDA approved the release of the first genetically engineered Human Insulin (Insulin produced by Genetech). Once completed, the cloning process lead to mass production of Humulin (under license by Eli Lilly).
- 1983 - Barbara McClintock was awarded the Nobel Prize in Physiology or Medicine in 1983 for her discovery of mobile genetic elements. McClintock studied transposon-mediated mutation and chromosome breakage in maize and published her first report in 1948 on transposable elements or transposons. She found that transposons were widely observed in corn however her ideas weren't widely granted attention until the 1960s and 1970s when the same phenomenon was discovered in bacteria and Drosophila melanogaster.
- 1983 - Kary Mullis of the Cetus Corporation drafted a technique for amplifying DNA through a cloning procedure that became known as polymerase chain reaction. Heat applied to the DNA segment causes it to separate, allowing the DNA polymerase to bind with the single strand of DNA. Taq polymerase (heat activated polymerase that synthesizes DNA, isolated from Thermophilus aquaticus) is necessary for polymerase chain reaction to work, because other polymerase proteins would denature in such physiological conditions. In the presence of an excess of mononucleotides, the polymerase will replicate the DNA and the process can be repeated a number of times, yielding an exponential growth of the number of DNA strands.
- 1985 - Alec Jeffreys announced DNA fingerprinting method. Jeffreys was studying DNA variation and the evolution of gene families in order to understand disease causing genes. In an attempt to develop a process to isolate many mini-satellites at once using chemical probes, Jeffreys took x-ray films of the DNA for examination and noticed that mini-satellite regions differ greatly from one person to another. In a DNA fingerprinting technique, a DNA sample is digested by treatment with specific nucleases or Restriction endonuclease and then the fragments are separated by electrophoresis producing a template distinct to each individual banding pattern of the gel.
- 1986 - Jeremy Nathans found genes for color vision and color blindness, working with David Hogness, Douglas Vollrath and Ron Davis as they were studying the complexity of the retina.
- 1989 - Thomas Cech discovered that RNA can catalyze chemical reactions, making for one of the most important breakthroughs in molecular genetics, because it elucidates the true function of poorly understood segments of DNA.
- 1992 - American and British scientists unveiled a technique for testing embryos in-vitro (Amniocentesis) for genetic abnormalities such as Cystic fibrosis and Hemophilia.
- 1993 - Phillip Allen Sharp and Richard Roberts discovered that genes in DNA are made up of introns and exons. According to their findings not all the nucleotides on the RNA strand (product of DNA transcription) are used in the translation process. The intervening sequences in the RNA strand are first spliced out so that only the RNA segment left behind after splicing would be translated to polypeptides.
- 1994 - The first breast cancer gene is discovered. BRCA I, was discovered by researchers at the King laboratory at UC Berkeley in 1990 but was first cloned in 1994). BRCA II, the second key gene in the manifestation of breast cancer was discovered later in 1994 by Professor Michael Stratton and Dr. Richard Wooster.
- 1996 - Alexander Rich discovered the Z-DNA, a type of DNA which is in a transient state, that is in some cases associated with DNA transcription. The Z-DNA form is more likely to occur in regions of DNA rich in cytosine and guanine with high salt concentrations.
- 1997 - Dolly the sheep was cloned by Ian Wilmut and colleagues from the Roslin Institute in Scotland.
- 2000 - The Drosophila melanogaster Genome is completed.
- 2003 - The Human Genome Project is officially completed after being funded by Congress in 1988. Within the limits of today's technology, the human genome is as complete as it can be. Small gaps that are unrecoverable in any current sequencing method remain, accounting for about 1 percent of the gene-containing portion of the genome, or euchromatin. New technologies will have to be invented to obtain the sequence of these regions.
- 2004 - Merck introduced a vaccine for Human Papillomavirus which promised to protect women against infection with HPV 16 and 18, which inactivates tumor suppressor genes and together cause 70% of cervical cancers.
- 2007 - Michael Worobey traced the evolutionary origins of HIV by analyzing its genetic mutations, which revealed that HIV infections had occurred in the United States as early as the 1960s.
- 2008 - Houston-based Introgen developed Advexin (FDA Approval pending), the first gene therapy for cancer and Li-Fraumeni syndrome, utilizing a form of Adenovirus to carry a replacement gene coding for the p53 protein.
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.210
- ^ Principles of Biochemistry / Nelson and Cox – 2005. pp.681
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.383-384
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). pp. 430-431
- ^ Modern Science-Hunter College High School Wiki—08/2009
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.99
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.147
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.109
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.190
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp. 212-213
- ^ Avery, O. T., MacLeod, C. M., McCarty, M. (1944) Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococal Types. Journal of Experimental Medicine. 79(2):137-156 
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.217 Table 9.1
- ^ Tamm, C., Herman, T., Shapiro, S., Lipschitz, R., Chargaff, E. (1953) Distribution Density of Nucleotides within a Desoxyribonucleic Acid Chain. Journal of Biological Chemistry. 203(2):673-688 
- ^ NATURE- Molecular Structure of Nucleic Acids / J.D. Watson, F.H.C. Crick Vol. 171(4356):737-738 (1953) 
- ^ Chemical Structure of the Nucleic Acids / Alexander R. Todd, 748-755,Vol. 40 (1954)
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 548
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. (Discovery of DNA polymerase I in E. Coli) pp.255
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 467-469
- ^ Crick FH, Barnett L, Brenner S, Watts-Tobin RJ (December 1961). "General nature of the genetic code for proteins". Nature 192: 1227–32.
- ^ Molecular Station: Structure of protein coding mRNA (2007)
- ^ Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. (Discovery of DNA polymerase I in E. Coli) pp.420
- ^ Genetics and Genomics Timeline: The discovery of messenger RNA (mRNA) by Sydney Brenner, Francis Crick, Francois Jacob and Jacques Monod 
- ^ Genetics, The hisB463 Mutation and Expression of a Eukaryotic Protein in Escherichia coli Vol. 180, 709-714, October 2008 
- ^ DNA Sequencing with Chain-Terminating Inhibitors / F. SANGER, S. NICKLEN, AND A. R. COULSON (1977)
- ^ Principles of Biochemistry / Nelson and Cox – 2005. pp.296-298
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). pp. 976 - 977
- ^ Patents 4 Life: Bertram Rowland 1930–2010. Biotech Patent Pioneer Dies (2010) 
- ^ Funding Universe: Genentech, Inc
- ^ The Significance of Responses of the Genome to Challenge / Barbara McClintock – Science New Series, Vol. 226, No. 4676 (1984), pp. 792-801 [http:%2/uhd.summon.serialssolutions.com/search?s.q=responses+of+the+genome+to+challenge&t.AuthorCombined=McClintock+Barbara&s.rf=PublicationDate%2C1984%3A*]
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). Pp. 763
- ^ Lemelson MIT Program—Inventor of the week: Alec Jeffreys – DNA FINGERPRINTING (2005) 
- ^ A. J. JEFFREYS*, V. WILSON* & S. L. THEIN / Letters to NATURE: Nature 316, 76 - 79 (1985) 
- ^ Wikidoc: Color Blindness – Inheritance pattern of Color Blindness (2010) 
- ^ Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 478
- ^ A Century of Nobel Prize Recipients / Francis Leroy - 2003. pp 345
- ^ NATURES / Perspectives: Z-DNA, The long road to biological function--Alexander Rich and Shuguang Zhang; Vol 4 (2003) 
- ^ The Journal of Biological Chemistry,284, e23-e25
- ^ CNN Interactive: A sheep cloning how-to, more or less(1997) http://www.cnn.com/TECH/9702/24/cloning.explainer/index.html
- ^ National Human Genome Research Institute / The Human Genome Project Completion: FAQs (2010) 
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