Although the science of genetics began with the applied and theoretical work of Gregor Mendel in the mid-1800s, other theories of inheritance preceded Mendel. A popular theory during Mendel's time was the concept of blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. Mendel's work disproved this, showing that traits are composed of combinations of distinct genes rather than a continuous blend. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children.^[7] Other theories included the pangenesis of Charles Darwin (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.^[8]

[edit] Mendelian and classical genetics

The modern science of genetics traces its roots to Gregor Johann Mendel, a German-Czech Augustinian monk and scientist who studied the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brünn, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically.^[9] Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.

The importance of Mendel's work did not gain wide understanding until the 1890s, after his death, when other scientists working on similar problems re-discovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905.^[10][11] (The adjective genetic, derived from the Greek word genesis—γένεσις, "origin" and that from the word genno—γεννώ, "to give birth", predates the noun and was first used in a biological sense in 1860.)^[12] Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London, England, in 1906.^[13]

After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1910, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.^[14] In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.^[15]

Morgan's observation of sex-linked inheritance of a mutation causing white eyes in Drosophila led him to the hypothesis that genes are located upon chromosomes.

[edit] Molecular genetics

Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA—scientists did not know which of these is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation (see Griffith's experiment): dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty identified the molecule responsible for transformation as DNA.^[16] The Hershey-Chase experiment in 1952 also showed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.^[17]

James D. Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA had a helical structure (i.e., shaped like a corkscrew).^[18][19] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what looks like rungs on a twisted ladder.^[20] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for duplication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand.

Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of protein production. It was discovered that the cell uses DNA as a template to create matching messenger RNA (a molecule with nucleotides, very similar to DNA). The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide and amino acid sequences is known as the genetic code.

With this molecular understanding of inheritance, an explosion of research became possible. One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger: This technology allows scientists to read the nucleotide sequence of a DNA molecule.^[21] In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of a DNA from a mixture.^[22] Through the pooled efforts of the Human Genome Project and the parallel private effort by Celera Genomics, these and other techniques culminated in the sequencing of the human genome in 2003.^[23]