Timeline of the history of genetics

This is a timeline of events concerning the Modern Evolution of Genetics, from Gregor Mendel to present day.

19th century

• 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 tangible 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 (an enzyme which breaks down proteins). From this, he recovered an acidic substance which he called "nuclein."^[1]
• 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.

1900s

• 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.^[2][3][4]
• 1904 - Walter Sutton and Theodor Boveri established the chromosome theory with their research which were done independent of each other and published in the years of 1902 to 1904. Boveri was studying sea urchins when 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.^[5] He concluded that this could be "the physical basis of the Mendelian law of heredity."^[6]
• 1908 - G.H. Hardy and Wilhelm Weinberg proposed the Hardy-Weinberg equilibrium model which describes the frequencies of alleles in the gene pool of a population, which are under certain specific conditions, as constant and at a state of equilibrium from generation to generation unless specific disturbing influences are introduced.

1910s

• 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.^[7] 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.^[8] A few years later, he constructed the world's first chromosome map.^[9]

1920s

• 1923 - Frederick Griffith studied bacterial transformation and observed that DNA carries genes responsible for pathogenicity.^[10]

1930s

• 1933 - Thomas Morgan received the Nobel prize for linkage mapping. His work elucidated the role played by the chromosome in heredity.

1940s

• 1941 - George Beadle and Edward Tatum, using Neurospora, demonstrated that genes code for enzymes.^[11]
• 1943 - Luria–Delbrück experiment: this experiment showed that genetic mutations conferring resistance to bacteriophage arise in the absence of selection, rather than being a response to selection.^[12]
• 1944 - Oswald Avery, Colin MacLeod and Maclyn McCarty refined the experiment done by Griffith in 1923. Their experiment on bacterial transformation involving the use of ribonuclease, protease, as well as deoxyribonuclease provided more evidence that DNA carries genetic information responsible for pathogenicity.^[13][14]
• 1947 – Salvador Luria discovered reactivation of irradiated bacteriophage,^[15] leading to numerous further studies of DNA repair processes in bacteriophage,^[16] as well as DNA repair processes in other organisms, including humans.

1950s

• 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 (guanine and adenine) are always found in the same amount as one another. Second, the concentration of purines (cytosine and thymidine) are also always the same. Lastly, Chargaff and his team found the proportion of pyrimidines and purines correspond each other.^[17][18]
• 1952 – The Hershey–Chase experiment provided key evidence that DNA, as distinct from protein, is the genetic material of a bacteriophage and thus the likely genetic material generally.^[19]
• 1953 - James Watson and Francis Crick with the contributions of Rosalind Franklin and Maurice Wilkins proposed a double helix model for the 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.^[20]
• 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.^[21]
• 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.^[22][23]
• 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.^[24]
• 1958 – The Meselson–Stahl experiment showed that DNA replication is semiconservative.^[25]

1960s

• 1960 – Jacob and collaborators discovered the operon, a group of genes whose expression is coordinated by an operator^[26][27]
• 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.^[28] These mutations were used to demonstrate that three sequential bases of the rIIB gene’s DNA specify each successive amino acid of the encoded protein. Thus the genetic code is a triplet code, where each triplet (called a codon) specifies a particular amino acid.
• 1961 - Sydney Brenner, Francois Jacob and Matthew Meselson identified the function of messenger RNA.^[29]
• 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.

1970s

• 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.^[30]
• 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.^[31]
• 1976 - Yeast genes expressed in E. coli for the first time.^[32]
• 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.^[33][34]

1980s

• 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.^[35]
• 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.^[36]
• 1982 - The U.S. Food and Drug Administration (FDA) approved the release of the first genetically engineered human insulin, originally biosynthesized using recombination DNA methods by Genentech in 1978.^[37] Once approved, the cloning process lead to mass production of humulin (under license by Eli Lilly & Co.).
• 1983 - Barbara McClintock was awarded the Nobel Prize in Physiology or Medicine 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, although her ideas weren't widely granted attention until the 1960s and 1970s when the same phenomenon was discovered in bacteria and Drosophila melanogaster.^[38]
• 1983 - Kary Mullis of the Cetus Corporation drafted a technique for amplifying DNA through a cloning procedure that became known as polymerase chain reaction.^[39] 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.^[40] 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.^[41]
• 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.^[42]
• 1989 - Thomas Cech discovered that RNA can catalyze chemical reactions,^[43] making for one of the most important breakthroughs in molecular genetics, because it elucidates the true function of poorly understood segments of DNA.

1990s

• 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 awarded the Nobel Prize for the discovery 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.^[44]
• 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.^[45] The Z-DNA form is more likely to occur in regions of DNA rich in cytosine and guanine with high salt concentrations.^[46]
• 1997 - Dolly the sheep was cloned by Ian Wilmut and colleagues from the Roslin Institute in Scotland.^[47]

2000s

• 2000 - The full genome sequence of Drosophila melanogaster 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.^[48]
• 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.

References

1. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.210
2. Principles of Biochemistry / Nelson and Cox – 2005. pp.681
3. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.383-384
4. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). pp. 430-431
5. O'Connor, C. & Miko, I. (2008) Developing the chromosome theory. Nature Education
6. Sutton, W. S. (1902) On the morphology of the chromosome group in Brachystola magna. Biological Bulletin. 4:24-3, pp. 39
7. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. p.99
8. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.147
9. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.109
10. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.190
11. Beadle GW, Tatum EL. Genetic Control of Biochemical Reactions in Neurospora. Proc Natl Acad Sci U S A. 1941 Nov 15;27(11):499-506. PMID 16588492
12. Luria SE, Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491-511. PMID 17247100
13. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp. 212-213
14. 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
15. Luria SE. Reactivation of Irradiated Bacteriophage by Transfer of Self-Reproducing Units. Proc Natl Acad Sci U S A. 1947 Sep;33(9):253-64. PMID 16588748
16. Bernstein C. Deoxyribonucleic acid repair in bacteriophage. Microbiol Rev. 1981 Mar;45(1):72-98. Review. PMID 6261109
17. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. pp.217 Table 9.1
18. 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
19. HERSHEY AD, CHASE M. Independent functions of viral protein and nucleic acid in growth of bacteriophage. J Gen Physiol. 1952 May;36(1):39-56. PMID 12981234
20. NATURE- Molecular Structure of Nucleic Acids / J.D. Watson, F.H.C. Crick Vol. 171(4356):737-738 (1953)
21. Chemical Structure of the Nucleic Acids / Alexander R. Todd, 748-755,Vol. 40 (1954)
22. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 548
23. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. (Discovery of DNA polymerase I in E. Coli) pp.255
24. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 467-469
25. Meselson M, Stahl FW. THE REPLICATION OF DNA IN ESCHERICHIA COLI. Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):671-82. PMID 16590258
26. Jacob F, Perrin D, Sánchez C, Monod J, Edelstein S. [The operon: a group of genes with expression coordinated by an operator. C.R.Acad. Sci. Paris 250 (1960) 1727-1729]. C R Biol. 2005 Jun;328(6):514-20. English, French. PMID 15999435
27. PERRIN D, SANCHEZ C, MONOD J. [Operon: a group of genes with the expression coordinated by an operator]. JACOB F, C R Hebd Seances Acad Sci. 1960 Feb 29;250:1727-9. French. PMID 14406329
28. Crick FH, Barnett L, Brenner S, Watts-Tobin RJ (December 1961). "General nature of the genetic code for proteins". Nature 192: 1227–32.
29. Molecular Station: Structure of protein coding mRNA (2007)
30. Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. (Discovery of DNA polymerase I in E. Coli) pp.420
31. Genetics and Genomics Timeline: The discovery of messenger RNA (mRNA) by Sydney Brenner, Francis Crick, Francois Jacob and Jacques Monod
32. Genetics, The hisB463 Mutation and Expression of a Eukaryotic Protein in Escherichia coli Vol. 180, 709-714, October 2008
33. DNA Sequencing with Chain-Terminating Inhibitors / F. SANGER, S. NICKLEN, AND A. R. COULSON (1977)
34. Principles of Biochemistry / Nelson and Cox – 2005. pp.296-298
35. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). pp. 976 - 977
36. Patents 4 Life: Bertram Rowland 1930–2010. Biotech Patent Pioneer Dies (2010)
37. Funding Universe: Genentech, Inc
38. 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*]
39. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008). Pp. 763
40. Lemelson MIT Program—Inventor of the week: Alec Jeffreys – DNA FINGERPRINTING (2005)
41. A. J. JEFFREYS*, V. WILSON* & S. L. THEIN / Letters to NATURE: Nature 316, 76 - 79 (1985)
42. Wikidoc: Color Blindness – Inheritance pattern of Color Blindness (2010)
43. Cell and Molecular Biology, Concepts and experiments / Gerald Karp –5th Ed (2008) pp. 478
44. A Century of Nobel Prize Recipients / Francis Leroy - 2003. pp 345
45. NATURES / Perspectives: Z-DNA, The long road to biological function--Alexander Rich and Shuguang Zhang; Vol 4 (2003)
46. The Journal of Biological Chemistry,284, e23-e25
47. CNN Interactive: A sheep cloning how-to, more or less(1997) http://www.cnn.com/TECH/9702/24/cloning.explainer/index.html
48. National Human Genome Research Institute / The Human Genome Project Completion: FAQs (2010)

External links

• http://www.hchs.hunter.cuny.edu/wiki/index.php?title=Modern_Science&printable=yes
• http://jem.rupress.org/content/79/2/137.full.pdf
• http://www.jbc.org/content/203/2/673.short
• http://www.nature.com/physics/looking-back/crick/Crick_Watson.pdf
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC534157/pdf/pnas00735-0082.pdf
• http://www.genomenewsnetwork.org/resources/timeline/1960_mRNA.php
• http://www.molecularstation.com/molecular-biology-images/data/503/MRNA-structure.png
• http://www.genomenewsnetwork.org/resources/timeline/1973_Boyer.php
• http://www.genetics.org/cgi/content/full/180/2/709
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC431765/pdf/pnas00043-0271.pdf
• http://www.nature.com/nature/journal/v316/n6023/abs/316076a0.html
• http://www.annualreviews.org/doi/abs/10.1146/annurev.bi.55.070186.003123
• http://www.cnn.com/TECH/9702/24/cloning.explainer/index.html
• http://www.genome.gov/11006943