The history of genetics can be represented on a timeline of events from the earliest work in the 1850s, to the DNA era starting in the 1940s, and the genomics era beginning in the 1970s.
Early timeline
1856–1863: 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.
1869: Friedrich Miescher discovers a weak acid in the nuclei of white blood cells that today we call DNA. In 1871 he isolated cell nuclei, 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.
1889: Hugo de Vries postulates that "inheritance of specific traits in organisms comes in particles", naming such particles "(pan)genes".[2]
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 gentisate, he noticed that it was prevalent among populations whose parents were closely related.[3][4][5]
1903: Walter Sutton and Theodor Boveri independently hypothesizes that chromosomes, which segregate in a Mendelian fashion, are hereditary units;[6] see the chromosome theory. 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.[7] He concluded that this could be "the physical basis of the Mendelian law of heredity."[8]
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.
1910: Thomas Hunt Morgan shows that genes reside on chromosomes while determining 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.[13]
1911: Alfred Sturtevant, one of Morgan's collaborators, invented the procedure of linkage mapping which is based on the frequency of crossing-over.[14]
1913: Alfred Sturtevant makes the first genetic map,[15] showing that chromosomes contain linearly arranged genes.
1920: Lysenkoism Started, during Lysenkoism they stated that the hereditary factor are not only in the nucleus, but also in the cytoplasm, though they called it living protoplasm.[16]
1930s–1950s: Joachim Hämmerling conducted experiments with Acetabularia in which he began to distinguish the contributions of the nucleus and the cytoplasm substances (later discovered to be DNA and mRNA, respectively) to cell morphogenesis and development.[18][19]
1931: Crossing over is identified as the cause of recombination; the first cytological demonstration of this crossing over was performed by Barbara McClintock and Harriet Creighton.
1933: Jean Brachet, while studying virgin sea urchin eggs, suggested that DNA is found in cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.[20][21]
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.[23]
1947: Salvador Luria discovers reactivation of irradiated phage,[25] stimulating numerous further studies of DNA repair processes in bacteriophage,[26] and other organisms, including humans.
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 thymine) are also always the same. Lastly, Chargaff and his team found the proportion of pyrimidines and purines correspond each other.[27][28]
1955: Joe Hin Tjio, while working in Albert Levan's lab, 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.[33]
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.[34][35][36]
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 a 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.[37]
1960: Jacob and collaborators discover the operon, a group of genes whose expression is coordinated by an operator.[39][40]
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.[41] 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.
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.[43]
1969: Molecular hybridization of radioactive DNA to the DNA of cytological preparation by Pardue, M. L. and Gall, J. G.
In the late 1970s: nonisotopic methods of nucleic acid labeling were developed. The subsequent improvements in the detection of reporter molecules using immunocytochemistry and immunofluorescence, in conjunction with advances in fluorescence microscopy and image analysis, have made the technique safer, faster and reliable.
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.[52]
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.[53]
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.[54] 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.[56]
Display of VNTR allele lengths on a chromatogram, a technology used in DNA fingerprinting 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.[57] 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.[58]
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.[59]
1987: Yoshizumi Ishino discovers and describes part of a DNA sequence which later will be called CRISPR.
1989: Thomas Cech discovered that RNA can catalyze chemical reactions,[60] 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 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.[62]
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.
1995: The genome of bacterium Haemophilus influenzae is the first genome of a free living organism to be sequenced.[63]
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.[64] The Z-DNA form is more likely to occur in regions of DNA rich in cytosine and guanine with high salt concentrations.[65]
2001: Francisco Mojica and Rudd Jansen propose the acronym CRISPR to describe a family of bacterial DNA sequences that can be used to specifically change genes within organisms.
Francis Collins announces the successful completion of the Human Genome Project in 2003 2003: Successful completion of Human Genome Project with 99% of the genome sequenced to a 99.99% accuracy.[67]
2003: Paul Hebert introduces the standardisation of molecular species identification and coins the term 'DNA Barcoding',[68] proposing Cytochrome Oxidase 1 (CO1) as the DNA Barcode for Animals.[69]
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.
2007: The Barcode of Life Data System (BOLD) is set up as an international reference library for molecular species identification.[70]
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.
2009: The Consortium for the Barcode of Life Project (CBoL) Plant Working Group propose rbcL and matK as the duel barcode for land plants.[71]
2011: Fungal Barcoding Consortium propose Internal Transcribed Spacer region (ITS) as the Universal DNA Barcode for Fungi.[72]
2012: The flora of Wales is completely barcoded, and reference specimens stored in the BOLD systems database, by the National Botanic Garden of Wales.[73]
2016: A genome is sequenced in outer space for the first time, with NASA astronaut Kate Rubins using a MinION device aboard the International Space Station.[74]
^Bateson, William (1907). "The Progress of Genetic Research". In Wilks, W. (ed.). Report of the Third 1906 International Conference on Genetics: Hybridization (the cross-breeding of genera or species), the cross-breeding of varieties, and general plant breeding. London: Royal Horticultural Society. Although the conference was titled "International Conference on Hybridisation and Plant Breeding", Wilks changed the title for publication as a result of Bateson's speech.
^Johannsen, Wilhelm (1909). Elemente der exakten Erblichkeitslehre [Elements of the exact theory of heredity] (in German). Jena, Germany: Gustav Fischer. p. 123. Johannsen distinguished between an organism's outward appearance (which he designated as its "phenotype") and its inherent genetic heritage (which he designated as its "genotype"). He stressed that an organism's appearance need not correspond exactly to its genetic heritage. So on p. 123 he defines "phenotype": "Darum könnte man den statistisch hervortretenden Typus passend als Erscheinungstypus bezeichnen oder, kurz und klar, als "Phaenotypus". 1) … Ein gebener Phaenotypus mag Ausdruck einer biologischen Einheit sein; er braucht es aber durchaus nicht zu sein. 1) Von φαίν-ομαι, scheinen." (Therefore one could designate the statistically prominent type appropriately as a type of appearance or, clearly and concisely, as a "phenotype". 1) … A given phenotype may be an expression of a biological unit; but it definitely need not be so. 1) From φαίν-ομαι, to appear.)
^Principles of Genetics / D. Peter Snustad, Michael J. Simmons – 5th Ed. p.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
^Hämmerling, J. (1953). "Nucleo-cytoplasmic Relationships in the Development of Acetabularia". International Review of Cytology Volume 2. Vol. 2. pp. 475–498. doi:10.1016/S0074-7696(08)61042-6. ISBN9780123643025.
^Mandoli, Dina F. (1998). What Ever Happened to Acetabularia? Bringing a Once-Classic Model System into the Age of Molecular Genetics. International Review of Cytology. Vol. 182. pp. 1–67. doi:10.1016/S0074-7696(08)62167-1. ISBN9780123645869.
^Brachet, J. (1933). Recherches sur la synthese de l'acide thymonucleique pendant le developpement de l'oeuf d'Oursin. Archives de Biologie 44* 519–576.
^Burian, R. (1994). Jean Brachet's Cytochemical Embryology: Connections with the Renovation of Biology in France? In: Debru, C., Gayon, J. and Picard, J.-F. (eds.). Les sciences biologiques et médicales en France 1920–1950, vol. 2 of Cahiers pour I'histoire de la recherche. Paris: CNRS Editions, pp. 207–220. link.
^Jacob, F; Perrin, D; Sánchez, C; Monod, J; Edelstein, S (June 2005). "[The operon: a group of genes with expression coordinated by an operator. C.R.Acad. Sci. Paris 250 (1960) 1727–1729]". Comptes Rendus Biologies. 328 (6): 514–20. doi:10.1016/j.crvi.2005.04.005. PMID15999435.
^Jacob, F; Perrin, D; Sanchez, C; Monod, J (February 1960). "[Operon: a group of genes with the expression coordinated by an operator]". C. R. Acad. Sci. 250: 1727–9. PMID14406329.
^Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, et al. (1976). "Complete nucleotide-sequence of bacteriophage MS2-RNA - primary and secondary structure of replicase gene". Nature. 260 (5551): 500–507. Bibcode:1976Natur.260..500F. doi:10.1038/260500a0. PMID1264203. S2CID4289674.
^Genetics, "The hisB463 Mutation and Expression of a Eukaryotic Protein in Escherichia coli", Vol. 180, 709–714, October 2008 [4]
^Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M, et al. (Feb 1977). "Nucleotide sequence of bacteriophage phi X174 DNA". Nature. 265 (5596): 687–95. Bibcode:1977Natur.265..687S. doi:10.1038/265687a0. PMID870828. S2CID4206886.
.jpg)
