Genetics (from the Greek genno γεννÏ = give birth) is the science of genes, heredity, evolution, and the variation of organisms. The phenomenon of inheritance has been implicitly utilized in breeding of organisms and selection for desired traits, and the scientific field of genetics seeks to understand the mechanisms of inheritance.
The genetic information of organisms is contained within the chemical structure of DNA (deoxyribonucleic acid) molecules. Individually inherited traits, corresponding to regions in the DNA sequence, are called genes. Genes encode the information necessary for synthesizing RNA and proteins -- complex molecules generally responsible for enzymatic reactions, synthesis, communication and structure within a cell. DNA sequence is transcribed into an intermediate molecule called "messenger RNA", and ribosomes translate this sequence to form a chain of amino acids to form a protein. This process is known as the central dogma of molecular biology.
Although genetics plays a large role in determining the appearance and behavior of organisms, it is the interaction of genetics with the environment that determines the ultimate outcome. Thus, while identical twins have the same DNA and genes, differences in their experiences during development and childhood results in different personalities and fingerprints.
Gregor Johann Mendel, a German-Czech Augustinian monk and scientist, is often called the "father of modern genetics", a title given to him due to his early work on the heredity of plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Brunn Natural History Society, Gregor Mendel traced the inheritance patterns of certain traits in pea plants and showed that they could be described mathematically. Although not all features show these patterns of Mendelian inheritance, his work suggested the utility of the application of statistics to the study of inheritance.
The significance of Mendel's observations 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. The word "genetics" itself was coined by William Bateson, a significant proponent of Mendel's work, in a letter to Adam Sedgwick, dated April 18, 1905. Bateson promoted the term "genetics" publicly in his inaugural address to the Third International Conference on Plant Hybridization (London, England) in 1906.
In the decades following rediscovery and popularization of Mendel's work, numerous experiments sought to elucidate the molecular basis of DNA. In 1910 Thomas Hunt Morgan argued that genes reside on chromosomes, based observations of a sex-linked white eye mutation in fruit flies. In 1913 his student Alfred Sturtevant used the phenomenon of genetic linkage and the associated recombination rates to demonstrate and map the linear arrangement of genes upon the chromosome.
Although chromosomes were known to contain genes, chromosomes were composed of both protein and DNA -- it was unknown which was critical for heredity or how the process occurred. In 1928, Frederick Griffith published his discovery of the phenomenon of transformation (see Griffith's experiment); sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty used this phenomenon to isolate and identify the molecule responsible for transformation as DNA. The Hershey-Chase experiment in 1952 identified DNA (rather than protein) as the genetic material of viruses, further evidence that DNA was the molecule responsible for inheritance .
James D. Watson and Francis Crick resolved the structure of DNA in 1953, using X-ray crystallography information that indicated the molecule had a helical structure. Their double-helix model paired a sequence of nucleotides with a "complement" on the other strand. This structure not only provided a physical explanation for information, contained within the order of the nucleotides, but also a physical mechanism for duplication through separation of strands and the reconstruction of a partner strand based on the nucleotide pairings. They famously observed this in their paper, stating: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
In the following decades, an explosion of research based on this understanding of the molecular nature of DNA became possible. The development of DNA sequencing in 1977 enabled the determination of nucleotide sequences on DNA, and the PCR method developed by Kary Banks Mullis in 1983 allowed the isolation and amplification of arbitrary segments of DNA. These and other techniques, through the pooled efforts of the Human Genome Project and parallel private effort by Celera Genomics, culminated in the sequencing of the human genome in 2001.
Timeline of notable discoveries
- 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
- 1903 Walter Sutton hypothesizes that chromosomes, which segregate in a Mendelian fashion, are hereditary units
- 1906 The term "genetics" is proposed by the British biologist William Bateson
- 1910 Thomas Hunt Morgan shows that genes reside on chromosomes, and discovered linked genes on chromosomes that do not follow Mendel's law of independent allele segregation
- 1913 Alfred Sturtevant makes the first genetic map of a chromosome, showing genes are linearly arranged
- 1918 Ronald Fisher publishes "The Correlation Between Relatives on the Supposition of Mendelian Inheritance" the modern synthesis starts.
- 1928 Frederick Griffith discovers a hereditary molecule that is transmissible between bacteria (see Griffiths experiment)
- 1931 Crossing over is the cause of recombination (see Barbara McClintock and cytogenetics)
- 1941 Edward Lawrie Tatum and George Wells Beadle show that genes code for proteins
- 1944 Oswald Theodore Avery, Colin McLeod and Maclyn McCarty isolate DNA as the genetic material (at that time called transforming principle)
- 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., the nucleotide bases Adenine-Thymine and Cytosine-Guanine always remain in equal proportions).
- 1950 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, with the help of Rosalind Franklin
- 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 The genetic code is arranged in triplets
- 1964 Howard Temin showed using RNA viruses that Watson's central dogma is not always true
- 1970 Restriction enzymes were discovered in studies of a bacterium, Haemophilus influenzae, enabling scientists to cut and paste DNA
- 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.
- 1976, Walter Fiers and his team determine the complete nucleotide-sequence of Bacteriophage MS2-RNA
- 1977 DNA is sequenced for the first time by Fred Sanger, Walter Gilbert, and Allan Maxam working independently. Sanger's lab complete the entire genome of sequence of Bacteriophage Φ-X174.
- 1983 Kary Banks Mullis discovers the polymerase chain reaction enabling the easy amplification of DNA
- 1985 Alec Jeffreys discovers genetic finger printing.
- 1989 The first human gene is sequenced by Francis Collins and Lap-Chee Tsui. It encodes the CFTR protein. 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, C. 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 98% of the genome sequenced to a 99.99% accuracy.
Areas of genetics
Classical genetics consists of the techniques and methodologies of genetics that predate the advent of molecular biology. After the discovery of the genetic code and such tools of cloning as restriction enzymes, the avenues of investigation open to geneticists were greatly broadened. Some classical genetic ideas have been supplanted with the mechanistic understanding brought by molecular discoveries, but many remain intact and in use, such as Mendel's laws and Muller's morphs. Patterns of inheritance still remain a useful tool for the study of genetic diseases.
Behavioral genetics studies the influence of varying genetics on animal behavior. Behavioral genetics studies the effects of human disorders as well as its causes. Behavioral genetics has yielded some very interesting questions about the evolution of various behaviors, and even some fundamental principles of evolution in general. For example, guppies and meerkats seem to be genetically driven to post a lookout to watch for predators. This lookout stands a significantly slimmer chance of survival than the others, so because of the mechanism of natural selection, it would seem that this trait would be lost after a few generations. However, the gene has remained, leading evolutionary philosopher/scientists such as Richard Dawkins and W. D. Hamilton to propose explanations, including the theories of kin selection and reciprocal altruism. The interactions and behaviors of gregarious creatures is partially genetic in cause and must therefore be approached by evolutionary theory.
Physicians who are trained as Geneticists diagnose, treat, and counsel patients with genetic disorders or syndromes. These doctors are typically trained in a genetics residency and/or fellowship.
Clinical genetics is also the study of genetic causes of clinical diseases.
Molecular genetics builds upon the foundation of classical genetics but focuses on the structure and function of genes at a molecular level. Molecular genetics employs the methods of both classical genetics (such as hybridization) and molecular biology. It is so-called to differentiate it from other sub fields of genetics such as ecological genetics and population genetics. An important area within molecular genetics is the use of molecular information to determine the patterns of descent, and therefore the correct scientific classification of organisms: this is called molecular systematics. The study of inherited features not strictly associated with changes in the DNA sequence is called epigenetics.
Some take the view that life can be defined, in molecular terms, as the set of strategies which RNA polynucleotides have used and continue to use to perpetuate themselves. This definition grows out of work on the origin of life, specifically the RNA world hypothesis.
Population, quantitative and ecological genetics
Population, quantitative and ecological genetics are all very closely related subfields and also build upon classical genetics (supplemented with modern molecular genetics). They are chiefly distinguished by a common theme of studying populations of organisms drawn from nature but differ somewhat in the choice of which aspect of the organism on which they focus. The foundational discipline is population genetics which studies the distribution of and change in allele frequencies of genes under the influence of the four evolutionary forces: natural selection, genetic drift, mutation and migration. It is the theory that attempts to explain such phenomena as adaptation and speciation.
The related subfield of quantitative genetics, which builds on population genetics, aims to predict the response to selection given data on the phenotype and relationships of individuals. A more recent development of quantitative genetics is the analysis of quantitative trait loci. Traits that are under the influence of a large number of genes are known as quantitative traits, and their mapping to a location on the chromosome requires accurate phenotypic, pedigree and marker data from a large number of related individuals.
Ecological genetics again builds upon the basic principles of population genetics but is more explicitly focused on ecological issues. While molecular genetics studies the structure and function of genes at a molecular level, ecological genetics focuses on wild populations of organisms, and attempts to collect data on the ecological aspects of individuals as well as molecular markers from those individuals.
Population genetics is closely linked with the methods of genetic epidemiology. One method to study gene-disease associations is using the principle of Mendelian randomization.
A more recent development is the rise of genomics, which attempts the study of large-scale genetic patterns across the genome for (and in principle, all the DNA in) a given species. The field typically depends on the availability of whole genome sequences, computational tools and Sequence profiling tool using bioinformatics approaches for analysis of large sets of data.
The science which grew out of the union of biochemistry and genetics is widely known as molecular biology. The term "genetics" is often widely conflated with the notion of genetic engineering, where the DNA of an organism is modified for some kind of practical end, but most research in genetics is aimed at understanding and explaining the effect of genes on phenotypes and in the role of genes in populations (see population genetics and ecological genetics), rather than genetic engineering.
- ^ a b Daniel Hartl and Elizabeth Jones (2005). Genetics: Analysis of Genes and Genomes, 6th edition. Jones & Bartlett. 854 pages. ISBN 0-7637-1511-5.
- ^ Robert C. King, Willliam D. Stansfield, Pamela K. Mulligan (2006). A Dictionary of Genetics, 7th edition. New York: Oxford University Press. 596 pages. ISBN 0-19-530761-5 (paper).
- ^ a b Mendel, G.. "Versuche über Pflanzen-Hybriden". Verh. Naturforsch. Ver. Brünn 4: 3-47. (in English in 1901, J. R. Hortic. Soc. 26: 1–32)
- ^ Online copy of William Bateson's letter to Adam Sedgwick
- ^ a b 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.
- ^ a b 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 on piese auto ieftine
- ^ a b 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):687-94
- ^ Ernest W. Crow and James F. Crow (2002). "100 Years Ago: Walter Sutton and the Chromosome Theory of Heredity". Genetics 160.
- ^ Beadle GW, Tatum EL (1941). "Genetic control of biochemical reactions in neurospora". PNAS 27: 499-506.
- ^ Watson JD and Crick FH (1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid". Nature 171 (4356): 737-8.
- ^ Meselson, M. and Stahl, F.W. (1958). "The Replication of DNA in Escherichia coli". PNAS 44: 671-82.
- ^ Min Jou W, Haegeman G, Ysebaert M, Fiers W. (1972). "Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein". Nature 237 (5350): 82-8.
- ^ Fiers W et al. (1976). "Complete nucleotide-sequence of Bacteriophage MS2-RNA - primary and secondary structure of replicase gene". Nature 260: 500-507.
- ^ http://www.genoscope.cns.fr/externe/English/Actualites/Presse/HGP/HGP_press_release-140403.pdf
- List of genetics-related topics
- List of genetic engineering topics
- Central dogma of molecular biology
- Gene gun
- Gene regulatory network
- Genetic counseling
- Genetic engineering
- Genetic screen
- Genetic testing
- Important publications in genetics
- List of genetics research organizations
- List of geneticists
- Human mitochondrial genetics
- Population genetics
- Punnett square
- Genetically modified food
- Transgenic plants
- American Journal of Human Genetics
- American Journal of Medical Genetics
- Annals of Human Genetics
- European Journal of Human Genetics
- Genome Research
- Human Molecular Genetics
- Journal of Genetics
- Journal of Human Genetics
- Journal of Medical Genetics
- Nature Reviews Genetics
- PLoS Genetics