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Alfred Russell Wallace publishes On the Law Which Has Regulated the Introduction of New Species
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Alfred Russell Wallace sends to Darwin a manuscript "On the Tendency of Varieties to Depart Indefinitely from the Original Type"
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Discovery of Natural selection: Charles Darwin wrote “On the Origin of Species by Means of Natural Selection, or the Preservation of Favored Races in the Struggle for Life.”
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Ernst Haeckel outlines the essential elements of modern zoological classification
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Modern Zoological classification: Ernst Haeckel (Häckel) outlines the essential elements of modern zoological classification
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Discovery of heredity transmitted in units:
Gregor Mendel’s experiments on peas demonstrate that heredity is transmitted in discrete units. The understanding that genes remain distinct entities even if the characteristics of parents appear to blend in their children explains how natural selection could work and provides support for Darwin’s proposal. -
EH Haeckel (Häckel) hypothesizes that the nucleus of a cell transmits its hereditary information
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Discovery of DNA Isolated: Frederick Miescher isolates DNA from cells for the first time and calls it “nuclein”.
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C Darwin publishes Descent of Man (principles of sexual selection)
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F Galton demonstrates the usefulness of twin studies for elucidating the relative influence of nature (heredity) and nurture (environment) upon behavioural traits
Oscar Hertwig concludes from a study of the reproduction of the sea urchin that fertilisation consists of the physical union of the two nuclei contributed by the male and female parents -
J Horner shows that colour-blindness is an inherited disease
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Fleming visualized chromosomes
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Discovery of Mitosis described: Walter Flemming describes chromosome behavior during animal cell division. He stains chromosomes to observe them clearly and describes the whole process of mitosis in 1882.
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August Weismann notes the distinction between somatic and germ cells; chromosomes observed by Walther Flemming in the nuclei of dividing salamander cells. He uses the word mitosis
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A Weismann postulates the reduction of chromosome number in germ cells
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W Waldeyer coins the word chromosome
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Johann Miescher isolates DNA from salmon sperm; F Galton publishes Natural Inheritance (biometry)
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A Weismann's book Das Keimplasma (The Germ Plasm) emphasizes meiosis as an exact mechanism of chromosome distribution
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William Bateson's Materials for the Study of Variation emphasizes the importance of discontinuous variations
Karl Pearson publishes his first contribution to the mathematical theory of evolution (he develops the Chi-squared test in 1900) -
EB Wilson publishes The Cell in Development and Heredity
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Discovery: Rediscovery of Mendel’s work
Botanists DeVries, Correns, and von Tschermak independently rediscover Mendel’s work while doing their own work on the laws of inheritance. The increased understanding of cells and chromosomes at this time allowed the placement of Mendel’s abstract ideas into a physical context. -
Discovery of Chromosome Theory of Inheritance:
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Discovery: : Orderly Inheritance of Disease
A British physician, Archibald Garrod, observes that the disease alkaptonuria is inherited according to Mendelian rules. This disease involves a recessive mutation, and was among the first conditions ascribed to a genetic cause. -
Discovery: The Word Gene is Coined
Wilhelm Johannsen coins the word “gene” to describe the Mendelian unit of heredity. He also uses the terms genotype and phenotype to differentiate between the genetic traits of an individual and its outward appearance. -
Thomas Hunt Morgan discovers the white-eye and its sex-linkage in Drosophila (the beginning of Drosophila genetics) [CPG p.63] [receives the Nobel prize in 1933]; J Herrick describes sickle cell anaemia
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Discovery: Chromosomes Carry Genes
Thomas Hunt Morgan and his students study fruit fly chromosomes. They show that chromosomes carry genes, and also discover genetic linkage. -
shows that genetic recombination does not take place in males in Drosophila
TH Morgan shows that genetic recombination does not take place in males in Drosophila and also discovers the first sex-linked lethal gene [Nobel prize 1933] -
S Wright works out the biochemical basis of coat colour inheritance in animals [CPG p.78]
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A Hungarian engineer, Karl Ereky, coins the term biotechnology (to mean production of beer, cheese, bread etc with the help of living organisms)
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CB Bridges proposes the balanced chromosome determination of sex theory [relationship between the autosomes and sex chromosomes] [CPG p.117]
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HJ Muller demonstrates that X-rays are mutagenic in Drosophila [CPG p.149] [receives the Nobel prize in 1946]
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F Griffith discovers type-transformation in pneumococcus
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Both women Harriet Creighton and Barbara McClintock had a background in genetics and worked together to publish a paper entitled
"“A Correlation of Cytological and Genetical Crossing-over in Zea mays". Drosophila melanogaster, or fruit flies, led him to develop a theory which stated that maternal and paternal chromosomes are the source of genetic variation (Britannica, n.d.). -
Jumping genes
It was discovered in 1940 that some genes can jump. -
In breeding corn, McClintock observed the “crossing over” of chromosomes.
The experiment which she conducted was very simple, but led to the understanding of a critical piece in the field of genetics. McClintock began her work using corn, a staining technique, and a microscope. Using the stain and the microscope she was able to identify single corn chromosomes. In breeding corn, McClintock observed the “crossing over” of chromosomes. This process usually takes place during prophase of meiosis I and involves an exchange. -
Discovery: One Gene, One Enzyme Hypothesis
George Beadle and Edward Tatum’s experiments on the red bread mold, Neurospora crassa, show that genes act by regulating distinct chemical events. They propose that each gene directs the formation of one enzyme -
Discovery: DNA Has a Regular Periodic Structure
William Astbury, a British scientist, obtains the first X-ray diffraction pattern of DNA, which reveals that DNA must have a regular periodic structure. He suggests that nucleotide bases are stacked on top of each other. -
Discovery: DNA Transforms Cells
Oswald Avery, Colin MacLeod, and Maclyn McCarty show that DNA (not proteins) can transform the properties of cells -- thus clarifying the chemical nature of genes. -
Discovery: Jumping Genes
Barbara McClintock, using corn as the model organism, discovers that genes can move around on chromosomes. This shows that the genome is more dynamic than previously thought. These mobile gene units are called transposons and are found in many species. -
Discovery: Genes Are Made of DNA
Alfred Hershey & Martha Chase show that only the DNA of a virus needs to enter a bacterium to infect it, providing strong support for the idea that genes are made of DNA -
Discovery: DNA Double Helix
Francis H. Crick and James D. Watson described the double helix structure of DNA. They receive the Nobel Prize for their work in 1962. -
Discovery: 46 Human Chromosomes
Joe Hin Tjio defines 46 as the exact number of chromosomes in human cells -
Discovery: DNA copying enzyme
Arthur Kornberg and colleagues isolated DNA polymerase, an enzyme that would later be used for DNA sequencing -
Discovery: Cause of Disease Traced to Alteration
Vernon Ingram discovers that a specific chemical alteration in a hemoglobin protein is the cause of sickle cell disease -
Discovery: Semiconservative Replication of DNA
Matthew Meselson and Franklin Stahl demonstrate that DNA replicates semiconservatively: each strand from the parent DNA molecule ends up paired with a new strand from the daughter generation. -
Discovery: Chromosome Abnormalities Identified
Jerome Lejeune and his colleagues discover that Down Syndrome is caused by trisomy 21. There are three copies, rather than two, of chromosome 21, and this extra chromosomal material interferes with normal development. -
Discovery: First Screen for Metabolic Defect in Newborns
Robert Guthrie develops a method to test newborns for the metabolic defect, phenylketonuria (PKU). -
Discovery: mRNA Ferries Information
Sydney Brenner, François Jacob and Matthew Meselson discover that mRNA takes information from DNA in the nucleus to the protein-making machinery in the cytoplasm. -
Discovery: Genetic Code Cracked
Marshall Nirenberg and others figure out the genetic code that allows nucleic acids with their 4 letter alphabet to determine the order of 20 kinds of amino acids in proteins. -
Discovery: First Restriction Enzyme Described
Scientists describe restriction nucleases, enzymes that recognize and cut specific short sequences of DNA. The resulting fragments can be used to analyze DNA, and these enzymes later became an important tool for mapping genomes. -
Discovery: First recombinant DNA
Scientists produce recombinant DNA molecules by joining DNA from different species and subsequently inserting the hybrid DNA into a host cell, often a bacterium. -
Discovery: First animal gene cloned
Researchers fuse a segment of DNA containing a gene from the African clawed frog Xenopus with DNA from the bacterium E. coli and placed the resulting DNA back into an E. coli cell. There, the frog DNA was copied and the gene it contained directed the production of a specific frog protein. -
Discovery: DNA Sequencing
Two groups, Frederick Sanger and colleagues, and Alan Maxam and Walter Gilbert, both develop rapid DNA sequencing methods. The Sanger method is most commonly employed in the lab today, with colored dyes used to identify each of the four nucleic acids that make up DNA. -
Discovery: First Genetic Engineering Company
Herbert Boyer founds Genentech. The company produces the first human protein in a bacterium, and by 1982 markets the first recombinant DNA drug, human insulin. -
Discovery: Introns Discovered
Richard Roberts’ and Phil Sharp’s labs show that eukaryotic genes contain many interruptions called introns. These noncoding regions do not directly specify the amino acids that make protein products. -
Discovery: First Transgenic Mice and Fruit Flies
Scientists successfully add stably inherited genes to laboratory animals. The resulting transgenic animals provide a new way to test the functions of genes. -
Discovery: GenBank Database Formed
Scientists begin submitting DNA sequence data to a National Institutes of Health (NIH) database that is open to the public -
Discovery: FLAVR SAVR Tomato
The Food And Drug Administration approves the sale of the first genetically modified food -
Discovery: Ban on Genetic Discrimination in the Workplace
Protection under the American with Disabilities Act is extended to cover discrimination based on genetic information -
Discovery: Mouse Genetic Map Completed
The lab mouse is valuable for genetics research because humans and mice share almost all of their genes, and the genes on average are 85% identical. The mouse genetic map increases the utility of mice as animal models for genetic disease in humans -
Discovery: E. coli Genome Sequenced
The complete sequence of the E. coli genome will help scientists learn even more about this extensively studied bacterium -
Discovery: M. tuberculosis Bacterium Sequenced
Mycobacterium tuberculosis causes the chronic infectious disease tuberculosis. The sequencing of this bacterium is expected to help scientists develop new therapies to treat the disease. -
Discovery: Roundworm C. elegans Sequenced
The first genome sequence of a multicellular organism, the roundworm, Caenorhabditis elegans, is completed. -
Discovery: Chromosome 22 Sequenced
The first finished, full-length sequence of a human chromosome is produced. Chromosome 22 was chosen to be first because it is relatively small and had a highly detailed map already available. Such a map is necessary for the clone by clone sequencing approach. -
Discovery: Human Genome Working Draft Completed
By the end of Spring 2000, HGP researchers sequence 90 percent of the human genome with 4-fold redundancy. This working draft sequence is estimated to be 99.9% accurate. -
Discovery: Mouse Genome Working Draft Assembled and Analyzed
The Mouse Genome Sequencing Consortium publishes an assembled draft and comparative analysis of the mouse genome. This milestone was originally planned for 2003.
2002. -
Discovery: Rat Genome Working Draft Completed
By Fall 2002, researchers sequence over 90% of the rat genome with over 5-fold redundancy. -
Discovery: Completion of the Human Genome Sequencing
The finished human genome sequence will be at least 99.99% accurate. -
Hypothetical scheme of adaptive immunity
In 2005 Francisco Mojica these sequences matched snippets from the genomes of bacteriophage (Mojica et al., 2005). This finding led him to hypothesize, correctly, that CRISPR is an adaptive immune system. -
Eugene Koonin, US National Center for Biotechnology Information, NIH
Koonin was studying clusters of orthologous groups of proteins by computational analysis and proposed a hypothetical scheme for CRISPR cascades as bacterial immune system based on inserts homologous to phage DNA in the natural spacer array, abandoning previous hypothesis that the Cas proteins might comprise a novel DNA repair system. (Makarova et al., 2006) -
Experimental demonstration of adaptive immunity
thermophilus is widely to make yogurt and cheese, and scientists wanted to explore how it responds to phage attac.Horvath showed experimentally that CRISPR systems are indeed an adaptive immune system: they integrate new phage DNA into the CRISPR array, which allows them to fight off the next wave of attacking phage .They showed that Cas9 is likely the only protein required for interference, the process by which the CRISPR system inactivates invading phage, details of which were not yet known. -
Spacer sequences are transcribed into guide RNAs
Scientists soon began to fill in some of the details on exactly how CRISPR-Cas systems “interfere” with invading phage. The first piece of critical information came from John van der Oost and colleagues who showed that in E-scherichia coli, spacer sequences, which are derived from phage, are transcribed into small RNAs, termed CRISPR RNAs (crRNAs), that guide Cas proteins to the target DNA (Brouns et al., 2008). -
CRISPR acts on DNA targets
CRISPR acts on DNA targets -
Cas9 cleaves target DNA
Moineau and colleagues demonstrated that CRISPR-Cas9 creates double-stranded breaks in target DNA at precise positions, 3 nucleotides upstream of the PAM (Garneau et al., 2010). They also confirmed that Cas9 is the only protein required for cleavage in the CRISPR-Cas9 system. This is a distinguishing feature of Type II CRISPR systems, in which interference is mediated by a single large protein (here Cas9) in conjunction with crRNAs. -
Discovery of tracrRNA for Cas9 system
The final piece to the puzzle in the mechanism of natural CRISPR-Cas9-guided interference came from the group of Emmanuelle Charpentier. They performed small RNA sequencing on Streptococcus pyogenes, which has a Cas9-containing CRISPR-Cas system. They discovered that in addition to the crRNA, a second small RNA exists, which they called trans-activating CRISPR RNA (tracrRNA). They showed that tracrRNA forms a duplex with crRNA, and that it is this duplex that guides Cas9 to its targets. -
CRISPR systems can function heterologously in other species
Siksnys and colleagues cloned the entire CRISPR-Cas locus from S. thermophilus (a Type II system) and expressed it in E. coli (which does not contain a Type II system), where they demonstrated that it was capable of providing plasmid resistance (Sapranauskas et al., 2011). This suggested that CRISPR systems are self-contained units and verified that all of the required components of the Type II system were known. -
CRISPR-Cas9 harnessed for genome editing
Similar findings as those in Gasiunas et al. were reported at almost the same time by Emmanuelle Charpentier in collaboration with Jennifer Doudna at the University of California, Berkeley (Jinek et al., 2012). Charpentier and Doudna also reported that the crRNA and the tracrRNA could be fused together to create a single, synthetic guide, further simplifying the system. (Although published in June 2012, this paper was submitted after Gasiunas et al.) -
Biochemical characterization of Cas9-mediated cleavage
Siksnys purified Cas9 in complex with crRNA from the E.coli strain engineered to carry the S.thermophilus CRISPR locus and undertook a series of biochemical exp to mechanistically characterize Cas9’s mode of action.Verified the cleavage site and requirement for PAM, using point mutations, showed that RuvC domain cleaves the non-complementary strand while HNH domain cleaves the complementary.Noted that crRNA could be trimmed down to a 20-nt stretch sufficient for efficient cleavage. -
CRISPR-Cas9 harnessed for genome editing
Zhang, who had previously worked on TALENs, was first to successfully adapt CRISPR-Cas9 for genome editing in eukaryotic cells. Zhang engineered two different Cas9 orthologs (from S. thermophilus and S. pyogenes) demonstrated targeted genome cleavage in human and mouse cells.Showed that the systemcould be programmed to target multiple genomic loci, and (ii) could drive homology-directed repair. Researchers from George Church’s lab at Harvard University reported similar findings in the same issue
