MAJOR ADVANCES IN GENETICS

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1 MAJOR ADVANCES IN GENETICS This document is licensed under the Attribution-NonCommercial-ShareAlike 2.5 Italy license, available at

2 1. The laws of inheritance 1866: Gregor Mendel publishes his findings on the laws of inheritance based on experiments with pea plants. He develops three principles : Dominance, Segregation, and Independent Assortment Dominance each inherited characteristic is determined by two alternative hereditary factors, and one factor is dominant over the other. Segregation the sex cell of a plant or animal may contain one factor (allele) for different traits but not both factors needed to express the traits. Independent assortment Different characteristics are inherited independently from each other.

3 2. Before the rediscovery 1871: Johann Friedrich Miescher isolates a substance which he calls NUCLEIN from the nuclei of white blood cells that was soluble in alkalis but not in acids. This substance came to be known as nucleic acid. 1882: german biologist Walter Flemming, by staining cells with dyes, discovers rod-shaped bodies he calls "chromosomes. He makes the first accurate counts of chromosome numbers and accurately drew the "longitudinal splitting" of chromosomes.

4 3. The rediscovery of Mendel s work Mendel s laws of inheritance are rediscovered in 1900, by the German botanist Carl Correns, the Dutch botanist Hugo De Vries, and the Austrian agronomist Erich von Tschermak.

5 4. Where do genes reside? In 1902, Walter Sutton (an American who at the time was a graduate student) and Theodor Boveri (a German biologist) recognized independently that the behavior of Mendel's particles during the production of gametes in peas precisely parallels the behavior of chromosomes at meiosis: 1) genes are in pairs (so are chromosomes); 2) the alleles of a gene segregate equally into gametes (so do the members of a pair of homologous chromosomes); 3) different genes act independently (so do different chromosome pairs). After recognizing this parallel behavior, both investigators reached the same conclusion that the parallel behavior of genes and chromosomes suggests that genes are located on chromosomes.

6 5. The word GENETICS is formulated 1903: William Bateson coins the terms genetics, F 1, F 2, Allelomorph (later shortened to allele), homozygote, heterozygote,, and epistasis. 1909: Danish botanist Wilhelm Johannsen proposes the term "gene" gene" " (from the Greek word "genos" which means "birth") to refer to a Mendelian hereditary factor. Johannsen also proposes two terms, genotype and phenotype,, to distinguish between one's genetic make-up and one's outward appearance.

7 6. Genes are lined-up on chromosomes 1915: Thomas Hunt Morgan, an American geneticist, publishes The Mechanism of Mendelian Heredity, in which he presents results from experiments with fruit flies that prove genes are lined up along chromosomes.. He also describes the principle of "linkage"" that alleles located relatively close to one another on a chromosome tend to be inherited together. By studying the frequency with which traits are inherited together, Morgan and co-workers create a "genetic" map" " of fruit fly chromosomes showing the relative locations of the genes responsible for dozens of traits, along with approximate distances between them on the chromosome. This work establishes the basis for gene mapping principles still used today.

8 7. Genes may cause quantitative variation 1918: R.A. Fisher shows that continuous traits can be explained by Mendelian segregation of genes: Mendel s laws give basis for statistical relationships between parents and offspring. His work reconciled the Darwinian view of evolution with the findings of the geneticists, posing the basis of the so-called Modern Synthesis

9 8. The first mutagenic agent In 1927 Herman Muller reported that X rays could induce mutations in male fruit flies. In his investigations Muller found that the mutation rate among the male fruit flies was linearly related to the radiation dose. His results supplied the first experimental evidence of a mutagen, in this case, the X rays. Muller's work on mutation induction opened the door to the genetic technique of using mutations to dissect biological processes, which is still used extensively today

10 9. The one-gene one-enzyme theory In 1941 G. W. Beadle and E. L. Tatum publish their classic study on the biochemical genetics of Neurospora and promulgate the one-gene, one-enzyme theory. They provide the experimental proof of a theory that has been proposed by Garrod more than 30 years before

11 10. Genes are made of DNA In 1944 O.T. Avery identifies deoxyribonucleic acid (DNA) as the "transforming principle. DNA extracted from dead pneumonia bacteria of a strain lethal to mice was capable of inducing virulence (lethality) in live but previously harmless strains In 1952 A. D. Hershey and M. Chase demonstrate that the DNA of phage enters the host, whereas most of the protein remains behind. In 1953 J. D. Watson and F. H. C. Crick propose a model for DNA comprised of two helically intertwined chains tied together by hydrogen bonds between the purines and the pyrimidines.

12 11. Genes are regulated in their expression 1961 F. Jacob and J. Monod publish "Genetic regulatory mechanisms in the synthesis of proteins," a paper in which the theory of the OPERON is developed. They found that the sugar glucose suppressed E. coli's ability to use other sugars, specifically the milk sugar lactose. When glucose was present, it was used it first. Only after the glucose had been consumed was lactose used. Intriguingly, there was "lag" between when glucose was used up and the bacteria started to grow on lactose. Francois Jacob Jaques Monod

13 12. The birth of genetic engineering In 1972 Paul Berg creates the first recombinant DNA molecules, combining in a single DNA molecule genes from different organisms. Results of his experiments, published in 1972, represented crucial steps in the subsequent development of genetic engineering. By his methods, individual genes could be isolated and inserted into mammalian cells or into such rapidly growing organisms as bacteria. The genes themselves could then be studied, and their protein products expressed and even manufactured in quantity. The prospect of recombinant DNA emerged from a series of advances in biochemistry most especially, from discoveries of new enzymes. Particularly important were the restriction enzymes that act as "scissors" to cut molecules of DNA at specific points. Similarly, ligases are enzymes that forge covalent bonds. The discovery of DNA ligase provided a kind of chemical soldering that could restore DNA after a foreign gene was spliced into it. These and other enzymes, captured from nature, could be used as tools in genetic engineering.

14 13. Genes can be sequenced In 1977 Walter Gilbert and Frederick Sanger devise techniques for sequencing DNA Molecular biologists by the 1970s had deciphered the genetic code and could spell out the sequence of amino acids in proteins. But inability to easily read off the precise nucleotide sequences of DNA forestalled further advances in molecular genetics and all prospects of genetic engineering. Walter Gilbert (with graduate student Allan M. Maxam) and Frederick Sanger, in 1977, working separately in the United States and England, developed new techniques for rapid DNA sequencing. Fred Sanger Sanger and Gilbert each took advantage of recently discovered enzymes and both methods benefited from improvements in gel electrophoresis, a method used for imaging the order of nucleotides. Walter Gilbert

15 14. A prodigious new technique In 1983 Kary Mullis conceives and helps develop polymerase chain reaction (PCR), a technology for rapidly multiplying fragments of DNA. The process is hailed as one of the monumental scientific techniques of the twentieth century; PCR multiplies a single, microscopic strand of the genetic material billions of times within hours.this invention would again revolutionize biotechnology and make the Human Genome Project possible.

16 15. The genome era 1995: The first completely sequenced genome of a self-replicating, free-living organism the bacteria Haemophilus influenzae 1996: Some 600 scientists around the world finished sequencing the genome of the yeast S. cerevisiae. 1998: A microscopic worm commonly used in genetic studies was the first multicellular organism to have its genome sequenced. The worm, called Caenorhabditis elegans, lives in soil and grows to be a millimeter in length. 1999: Drosophila's entire genome was sequenced and assembled by Celera Genomics, in conjunction with the federally funded Berkeley Drosophila Genome Project (BDGP), in the course of about eight months. 2000: On June 26, 2000, Celera Genomics' and the International Human Genome Project made a joint announcement they had finished a "working draft" of the genome at the White House in the United States, during a major news event to mark an historic milestone.