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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.
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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
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Karl Pearson publishes his first contribution to the mathematical theory of evolution (he develops the Chi-squared test in 1900)
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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.
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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.
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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.
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Thomas Hunt Morgan and his students study fruit fly chromosomes. They show that chromosomes carry genes, and also discover genetic linkage.
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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]
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"“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.).
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It was discovered in 1940 that some genes can jump.
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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.
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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
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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.
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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.
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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.
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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
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Francis H. Crick and James D. Watson described the double helix structure of DNA. They receive the Nobel Prize for their work in 1962.
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Joe Hin Tjio defines 46 as the exact number of chromosomes in human cells
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Arthur Kornberg and colleagues isolated DNA polymerase, an enzyme that would later be used for DNA sequencing
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Vernon Ingram discovers that a specific chemical alteration in a hemoglobin protein is the cause of sickle cell disease
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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.
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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.
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Robert Guthrie develops a method to test newborns for the metabolic defect, phenylketonuria (PKU).
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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.
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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.
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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.
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Scientists produce recombinant DNA molecules by joining DNA from different species and subsequently inserting the hybrid DNA into a host cell, often a bacterium.
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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.
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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.
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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.
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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.
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Scientists successfully add stably inherited genes to laboratory animals. The resulting transgenic animals provide a new way to test the functions of genes.
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Scientists begin submitting DNA sequence data to a National Institutes of Health (NIH) database that is open to the public
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The Food And Drug Administration approves the sale of the first genetically modified food
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Protection under the American with Disabilities Act is extended to cover discrimination based on genetic information
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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
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The complete sequence of the E. coli genome will help scientists learn even more about this extensively studied bacterium
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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.
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The first genome sequence of a multicellular organism, the roundworm, Caenorhabditis elegans, is completed.
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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.
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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.
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The Mouse Genome Sequencing Consortium publishes an assembled draft and comparative analysis of the mouse genome. This milestone was originally planned for 2003.
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By Fall 2002, researchers sequence over 90% of the rat genome with over 5-fold redundancy.
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The finished human genome sequence will be at least 99.99% accurate.
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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.
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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)
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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.
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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).
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CRISPR acts on DNA targets
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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.
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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.
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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.
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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.)
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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.
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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
