History of genetics

  The history of genetics is generally held to have started with the work of an Augustinian monk, Gregor Mendel. His work on pea plants, published in 1866, described what came to be known as Mendelian inheritance. In the centuries before—and for several decades after—Mendel's work, a wide variety of theories of heredity proliferated. 1900 marked the "rediscovery of Mendel" by Hugo de Vries, Carl Correns and Erich von Tschermak, and by 1915 the basic principles of Mendelian genetics had been applied to a wide variety of organisms—most notably the fruit fly Drosophila melanogaster. Led by Thomas Hunt Morgan and his fellow "drosophilists", geneticists developed the Mendelian-chromosome theory of heredity, which was widely accepted by 1925. Alongside experimental work, mathematicians developed the statistical framework of population genetics, bring genetical explanations into the study of evolution.

With the basic patterns of genetic inheritance established, many biologists turned to investigations of the physical nature of the gene. In the 1940s and early 1950s, experiments pointed to DNA as the portion of chromosomes (and perhaps other nucleoproteins) that held genes. A focus on new model organisms such as viruses and bacteria, along with the discovery of the double helical structure of DNA in 1953, marked the transition to the era of molecular genetics. In the following years, chemists developed techniques for sequencing both nucleic acids and proteins, while others worked out the relationship between the two forms of biological molecules: the genetic code. The regulation of gene expression became a central issue in the 1960s; by the 1970s gene expression could be controlled and manipulated through genetic engineering. In the last decades of the 20th century, many biologists focused on large-scale genetics projects, sequencing entire genomes.

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Pre-Mendelian ideas on heredity

See also: Heredity

Ancient theories

The most influential early theories of heredity were that of Hippocrates and Aristotle. Hippocrates' theory (possibly based on the teachings of Anaxagoras) was similar to Darwin's later ideas on pangenesis, involving heredity material that collects from throughout the body. Aristotle suggested instead that the (nonphysical) form-giving principle of an organism was transmitted through semen, determining the shape of the female's menstrual blood through an organism's early development. For both Hippocrates and Aristotle—and nearly all Western scholars through to the late 19th century—the inheritance of acquired characters was a supposedly well-established fact that any adequate theory of heredity had to explain. At the same time, individual species were taken to have a fixed essence; such inherited changes were merely superficial.^[1]

Plant systematics and hybridization

See also: History of plant systematics

In the 18th century, with increased knowledge of plant and animal diversity and the accompanying increased focus on taxonomy, new ideas about heredity began to appear. Linnaeus and others (among them Joseph Gottlieb Kölreuter, Carl Friedrich von Gärtner, and Charles Naudin) conducted extensive experiments with hybridization, especially species hybrids. Species hybridizers described a wide variety of inheritance phenomena, include hybrid sterility and the high variability of back-crosses.^[2]

Plant breeders were also developing an array of stable varieties in many important plant species. In the early 19th century, Augustin Sageret established the concept of dominance, recognizing that when some plant varieties are crossed, certain characters (present in one parent) usually appear in the offspring; he also found that some ancestral characters found in neither parent may appear in offspring. However, plant breeders made little attempt to develop a theoretical foundation for their work or to integrate their knowledge with work in physiology and natural history.^[3]

Mendel

In breeding experiments between 1856 and 1865, Gregor Mendel first traced inheritance patterns of certain traits in pea plants and showed that they obeyed simple statistical rules. Although not all features show these patterns of Mendelian inheritance, his work acted as a proof that application of statistics to inheritance could be highly useful. Since that time many more complex forms of inheritance have been demonstrated.

From his statistical analysis Mendel defined a concept that he described as an allele, which was the fundamental unit of heredity. The term allele as Mendel used it^{[citation needed]} is nearly synonymous with the term gene, and now means a specific variant of a particular gene.

Mendel's work was published in 1866 as Experiments on Plant Hybridization in the Proceedings of the Natural History Society of Brünn, following two lectures he gave on the work in early 1865.

Post-Mendel, pre-re-discovery

Mendel's work was published in a relatively obscure scientific journal, and it was not given any attention in the scientific community. Instead, discussions about modes of heredity were galvanized by Darwin's theory of evolution by natural selection, in which mechanisms of non-Lamarckian heredity seemed to be required. Darwin's own theory of heredity, pangenesis, did not meet with any large degree of acceptance. A more mathematical version of pangenesis, one which dropped much of Darwin's Lamarckian holdovers, was developed as the "biometrical" school of heredity by Darwin's cousin, Francis Galton. Under Galton and his successor Karl Pearson, the biometrical school attempted to build statistical models for heredity and evolution, with some limited but real success, though the exact methods of heredity were unknown and largely unquestioned.

Classical genetics

The significance of Mendel's work was not understood until early in the twentieth century, after his death, when his research was re-discovered by other scientists working on similar problems. Hugo de Vries, Carl Correns and Erich von Tschermak

There was then a feud between Bateson and Pearson over the hereditary mechanism. Fisher solved this in The Correlation Between Relatives on the Supposition of Mendelian Inheritance

1865 Gregor Mendel's paper, Experiments on Plant Hybridization

1869 Friedrich Miescher discovers a weak acid in the nuclei of white blood cells that today we call DNA

1880-1890 Walther Flemming, Eduard Strasburger, and Edouard van Beneden elucidate chromosome distribution during cell division

1889 Hugo de Vries postulates that "inheritance of specific traits in organisms comes in particles", naming such particles "(pan)genes" ^[4]

1903 Walter Sutton hypothesizes that chromosomes, which segregate in a Mendelian fashion, are hereditary units^[5]

1905 William Bateson coins the term "genetics" in a letter to Adam Sedgwick^[6] and at a meeting in 1906 ^[7]

1908 Hardy-Weinberg law derived.

1910 Thomas Hunt Morgan shows that genes reside on chromosomes

1913 Alfred Sturtevant makes the first genetic map of a chromosome

1913 Gene maps show chromosomes containing linear arranged genes

1918 Ronald Fisher publishes "The Correlation Between Relatives on the Supposition of Mendelian Inheritance" the modern synthesis of genetics and evolutionary biology starts. See population genetics.

1928 Frederick Griffith discovers that hereditary material from dead bacteria can be incorporated into live bacteria (see Griffiths experiment)

1931 Crossing over is identified as the cause of recombination

1933 Jean Brachet is able to show that DNA is found in chromosomes and that RNA is present in the cytoplasm of all cells.

1941 Edward Lawrie Tatum and George Wells Beadle show that genes code for proteins; see the original central dogma of genetics

The DNA era

1944 Oswald Theodore Avery, Colin McLeod and Maclyn McCarty isolate DNA as the genetic material (at that time called transforming principle)^[8]

1950 Erwin Chargaff shows that the four nucleotides are not present in nucleic acids in stable proportions, but that some general rules appear to hold (e.g., that the amount of adenine, A, tends to be equal to that of thymine, T). Barbara McClintock discovers transposons in maize

1952 The Hershey-Chase experiment proves the genetic information of phages (and all other organisms) to be DNA

1953 DNA structure is resolved to be a double helix by James D. Watson and Francis Crick^[9]

1956 Joe Hin Tjio and Albert Levan established the correct chromosome number in humans to be 46

1958 The Meselson-Stahl experiment demonstrates that DNA is semiconservatively replicated

1961-1967 Combined efforts of scientists "crack" the genetic code, including Marshall Nirenberg, Har Gobind Khorana, Sydney Brenner & Francis Crick

1964 Howard Temin showed using RNA viruses that the direction of DNA to RNA transcription can be reversed

1970 Restriction enzymes were discovered in studies of a bacterium, Haemophilus influenzae, enabling scientists to cut and paste DNA

The genomics era

See genomics, history of genomics

1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent (Ghent, Belgium) were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein^[10].

1976, Walter Fiers and his team determine the complete nucleotide-sequence of bacteriophage MS2-RNA^[11]

1977 DNA is sequenced for the first time by Fred Sanger, Walter Gilbert, and Allan Maxam working independently. Sanger's lab sequence the entire genome of Bacteriophage Φ-X174^[12].

1983 Kary Banks Mullis discovers the polymerase chain reaction enabling the easy amplification of DNA

1989 The human gene that encodes the CFTR protein was sequenced by Francis Collins and Lap-Chee Tsui. Defects in this gene cause cystic fibrosis.

1995 The genome of Haemophilus influenzae is the first genome of a free living organism to be sequenced

1996 Saccharomyces cerevisiae is the first eukaryote genome sequence to be released

1998 The first genome sequence for a multicellular eukaryote, Caenorhabditis elegans, is released

2001 First draft sequences of the human genome are released simultaneously by the Human Genome Project and Celera Genomics.

2003 (14 April) Successful completion of Human Genome Project with 99% of the genome sequenced to a 99.99% accuracy [2]

See also

• List of sequenced eukaryotic genomes

Further reading

• Elof Axel Carlson, Mendel's Legacy: The Origin of Classical Genetics (Cold Spring Harbor Laboratory Press, 2004.) ISBN 0-87969-675-3

References

1. ^ Mayr, The Growth of Biological Thought, pp 635-640
2. ^ Mayr, The Growth of Biological Thought, pp 640-649
3. ^ Mayr, The Growth of Biological Thought, pp 649-651
4. ^ Vries, H. de (1889) Intracellular Pangenesis [1] ("pan-gene" definition on page 7 and 40 of this 1910 translation in English)
5. ^ Ernest W. Crow and James F. Crow (2002). "100 Years Ago: Walter Sutton and the Chromosome Theory of Heredity". Genetics 160.
6. ^ Online copy of William Bateson's letter to Adam Sedgwick
7. ^ Bateson, William (1907). "The Progress of Genetic Research". Wilks, W. (editor) 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.

8. ^ Avery, MacLeod, and McCarty (1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine 79 (1): 137-58.35th anniversary reprint available
9. ^ Watson JD, Crick FH, Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid, Nature. 1953 Apr 25;171(4356):737-8
10. ^ Min Jou W, Haegeman G, Ysebaert M, Fiers W., Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein, Nature. 1972 May 12;237(5350):82-8
11. ^ Fiers W et al., Complete nucleotide-sequence of bacteriophage MS2-RNA - primary and secondary structure of replicase gene, Nature, 260, 500-507, 1976
12. ^ Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M., Nucleotide sequence of bacteriophage phi X174 DNA, Nature. 1977 Feb 24;265(5596):687-95