|1745||Maupertuis proposes an adaptationist account of organic design||Presupposes some mechanism for transmitting adaptations|
|1859||Darwin publishes The Origin of Species, vastly strengthening the adaptationist hypothesis|
|1865||Gregory Mendel publishes evidence for the discreteness and combinatorial rules of inherited traits||Traits are carried by discrete units, or genes; the results are not appreciated until 1900|
|1869||Miescher discovers "nuclein" (DNA) in the cells from pus in open wounds -- cells composed mostly of nuclear material. It became known as nucleic acid after 1874, when Miescher separated it into a protein and an acid molecule.||Suspected of exerting some function in the hereditary process|
|1918-1926||Muller formulates the chief principles of spontaneous gene mutation as point effects of ultramicroscopic physico-chemical accidents; he induces such changes using X-rays||The gene constitutes the basis of life and evolution by virtue of its property of reproducing its own internal changes|
|1920s||Nucleic acid found to be a major component of the chromosomes||Its molecular structure was thought to be simple, so it was not a good candidate for a carrier of genetic information|
|1930s||Chemical nature of nuclei acid investigated. It was thought to be a tetranucleotide composed of one unit each of adenylic, guanylic, thymidylic and cytidylic acids||The ubiquitous presence of nucleic acid in the chromosome was generally explained in purely physiological or structural terms|
|The molecular weight of nucleic acid was found to be much higher than the tetranucleotide hypothesis required, but it was still viewed as a uniform polymer, like starch, unaffected by its biological source||Hereditary information was commonly thought to reside in the chromosomal proteins, since these differ across species, between individuals, and even within an organism|
|1944||Oswald Avery identifies nucleic acids as the active principle in bacterial transformation||"If the results of the present study of the transforming principle are confirmed, then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined."|
|1950||Erwin Chargaff shows that the four nucleotides are not present in nucleic acids in stable proportions, and that the nucleotide composition differs according to its biological source.||The nucleic acids are not monotonous polymers.|
|1952||Alfred Hershey and Martha Chase show that on infection of the host bacterium by a virus, at least 80% of the viral DNA enters the cell and at least 80% of the viral protein remains outside.||DNA rather than proteins carry genetic information.|
|1953||Watson and Crick determine that deoxyribonucleic acid (DNA) is a double-strand helix of nucleotides. Each nucleotide consists of a deoxyribose sugar molecule to which is attached a phosphate group and one of four nitrogenous bases: two purines (adenine and guanine) and two pyrimidines (cytosine and thymine). The nucleotides are joined together by covalent bonds between the phosphate of one nucleotide and the sugar of the next, forming a phosphate-sugar backbone from which the nitrogenous bases protrude. The two strands are linked by selective hydrogen bonds: the purine adenine bonds only with the pyrimidine thymine, and the purine cytosine only with the pyrimidine guanine.||DNA replication is possible through the complementary nature
of the two strands. The chemical complexity of the molecule is thought
to be sufficient to store the requisite information.
The precise manner in which the information in the DNA is activated to build an organism is still very poorly understood; what is firmly demonstrated is that so-called structural genes manufacture the proteins for living tissues.
|Early 1970s||Comparisons between chimpanzee and human genomes finds that they diverge by only 1.6%--less than most sibling species, which barely differ in morphology, and far less than that between any pair of congeneric species (King & Wilson 1975: 113)||The theoretical implications are unclear; morphological and behavioral differences between the two species appeared to be unaccounted for by the genetic material (cf. Cherry et al, 1978; for an update, see Gibbons 1998).|
|Early 1970s||The discovery of regulator genes--genes that control the timing and output of structural genes||Since a regulator gene may control thousands of structural genes, and indeed other regulator genes, the logical inference is that human and chimpanzee genomes are being switched on and off in quite different ways (King & Wilson 1975)|
|1980s||McClintock discovered transposable strands of genes in maize already in the 1940s, but her work was not fully recognized for a generation.||The genome may be controlling aspects of its own mutation (see Pennisi 1998 and Chicurel 2001 for an overview).|
|1984||McGinnis discovers homeotic (Hox) regulatory genes, responsible for the basic body plan of most animals. In subsequent work, his team demonstrates that a single mutation in a Hox gene suffices to suppress all limb development in the thoracic region of fruit flies.||Macroevolutionary transitions, such as that from arthropods to hexapods (insects), may be initiated by point changes in regulatory genes.|
|2000||The Human Genome Project presents its preliminary results: each of the body's 100 trillion cells contains some 3.1 billion nucleotide units. Only 1% of these are thought to be transcriptional, clustered in possibly as few as 30,000 genes.||An accurate chemical map of the genome tells us surprisingly little about how it functions. Targeted experimentation is now possible.|
|Avery, O. T., C. M. MacLeod, and M. McCarty (1944).
Studies on the Chemical Nature of Substance Inducing Transformation of
Pneumococcal Typoes. Induction of Transformation by a Desoxyribonucleic
Acid Fraction Isolated from Pneumococcus Type III. Journal of
Experimental Medicine 79: 137-158. Also in Peters
Oswald Avery (1877-1955) was a bacteriologist whose research on pneumococcus bacteria made him one of the founders of immunochemistry and laid the foundation for later discoveries that launched the science of molecular genetics.
|Castle, William Ernest (1903). Mendel's Law of Heredity. Cambridge, MA.|
|Chargaff, Erwin, ed. (1955-60). The Nucleic Acids: Chemistry and Biology. New York, Academic Press.|
|Chargaff, Erwin (1989). In Retrospect. A Commentary on Studies on the Structure of Ribonucleic Acids. Biochimica et Biophysica Acta 1000: 15-33.|
|Cherry, L.M., S.M. Case and A.C. Wilson (1978). Frog perspective on the morphological difference between humans and chimpanzees. Science 200: 209-211.|
Research by cell and molecular biologists suggest that in times of stress, organisms may be able to crank up their mutation rates, helping accelerate their own evolution.
|Hershey, Alfred D. and Martha Chase (1952).
Independent functions of viral protein and nucleic acid in growth of bacteriophage.
Journal of General Physiology 36: 39-56.
Hershey was awarded the Nobel Prize in 1969 for his work on the fundamental role of nucleic acid in the transmission of inherited characteristics. His best-known experiment was carried out in 1952 with his assistant Martha Chase at the Cold Spring Harbor (N.Y.) Laboratory. Their work, often referred to as the "blender experiment" in deference to the common household appliance they employed, demonstrated that DNA alone, and not protein, is the stuff of which genes are made. See the biography at the Cold Springs Harbor site (external).
|Human Genome Project, run by The International Human Genome Sequencing Consortium; see Human Genome Central at Ensembl for details; BBC online provides a quick project timeline. The first analysis of the preliminary data was published in a series of articles in Nature 15 Feb 2001; see press releases at the NIH's site.|
|King, M.C. and A.C. Wilson (1975). Evolution at two levels in Humans and Chimpanzees. Science 188: 107-116.|
Maupertuis, Pierre Louis Moreau de (1745). Venus physique. La Haye. Excerpt.
|McClintock, Barbara (1987). The Discovery
and Characterization of Transposable Elements: The Collected Papers of
Barbara McClintock. New York: Garland, 1987.
In her 1983 Nobel lecture, McClintock said the genome is "a highly sensitive organ of the cell, that in times of stress could initiate its own restructuring and renovation." See the biography at the Cold Springs Harbor site (external). For a current discussion, see Pennisi 1998.
McGinnis W, M.S. Levine, E. Hafen, A. Kuroiwa, W.J. Gehring (1984). A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 4. 308 (5958): 428-33. Abstract (external).
Ronshaugen, Matthew, Nadine McGinnis, and William McGinnis (2002). Hox protein mutation and macroevolution of the insect body plan. Nature 10. 1038 (716), advance online publication. Full text (external, PDF). UCSD press release.
For a discussion, see Holland, Peter W.H. (1999). The future of evolutionary developmental biology. Nature 402: C41 - C44. Full text (external). For further background, see Lawrence, P.A. (1992). The Making of a Fly: The Genetics of Animal Design. New York: Blackwell.
|Mendel, Gregor (1963). Experiments in Plant Hybridisation. Cambridge, MA: Harvard University Press. His work, in German, was first published in 1865 in the Proceedings of the Brünn Society for Natural History, Brünn, Austria (Hewlett, 1998). It was ignored for a generation.|
|Miescher, Johann Friedrich (1871). Still
looking for title and place of publication. Miescher's 1869 work was not
published until 1871 (Dictionary of Scientists, 1999).
Johann Friedrich Miescher (1844-1895; see external portrait) was a Swiss student of cell metabolism. He discovered the nucleic acids in 1869, first in white blood cells from the pus in bandages from the Crimean war (Hewlett, 1998), later in salmon spermatozoa. The significance of his work was not realized for several decades.
The most in-depth study of his work and influence is Julius Reiner's dissertation, Der Beitrag von Friedrich Miescher d. J., 1844-1895, zur Geschichte der Zellbiologie, Basel, 1963 (The Contribution of Friedrich Miescher, Jr., 1844-1895, to the History of Cell Biology -- there does not appear to be an English translation). See also Blanchard (1998).
Muller (1890-1967) received the Nobel Prize in Physiology or Medicine in 1946 for his work on the induction of mutations by X-rays.
|Peters, James Arthur (1959). Classic Papers in Genetics. Englewood Cliffs, NJ: Prentice-Hall.|
|Pennisi, Elizabeth (1998). How the genome readies itself for evolution. Science 281. 5380: 1131-1134. Abstract and full text.|
|Watson and Crick (1953). A Structure for Deoxyribonucleic Acid. Nature|
|Related links and literature
Blanchard, Susan M. (1998). Friedrich Miescher, 1868. The early history of cell biology. Full text (external).
Cairns, John, Gunther Stent, and James Watson (eds.) (1992/1966). Phage and the Origins of Molecular Biology." New York: Cold Spring Harbor Press.
A Dictionary of Scientists (1999). New York, NY: Oxford University Press. Miescher entry (external).
Hewlett, Martin (1998). From Mendel to Biotechnology: A Critical Look at the Historical Development and Philosophical Foundations of Modern Biology. Full text (external).
Judson, Horace F. (1996). The Eighth Day of Creation. Cold Spring Harbor Press, New York. An excellent source on the early history of biology.
Lane, Jo Ann (1994). History of Genetics Timeline.
Schrödinger, Erwin (1944). What is Life. Cambridge, UK: Cambridge University Press.
Stent, Gunther S. (1978). Paradoxes of Progress. San Francisco: Freeman. 95-109.
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