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Directed Evolution
Directed evolution (DE) is a method used in protein engineering that mimics the process of natural selection to steer proteins or nucleic acids toward a user-defined goal. It consists of subjecting a gene to iterative rounds of mutagenesis (creating a library of variants), selection (expressing those variants and isolating members with the desired function) and amplification (generating a template for the next round). It can be performed '' in vivo'' (in living organisms), or '' in vitro'' (in cells or free in solution). Directed evolution is used both for protein engineering as an alternative to rationally designing modified proteins, as well as for experimental evolution studies of fundamental evolutionary principles in a controlled, laboratory environment. History Directed evolution has its origins in the 1960s with the evolution of RNA molecules in the "Spiegelman's Monster" experiment. The concept was extended to protein evolution via evolution of bacteria under s ...
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Frances Arnold
Frances Hamilton Arnold (born July 25, 1956) is an American chemical engineer and Nobel Laureate. She is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology (Caltech). In 2018, she was awarded the Nobel Prize in Chemistry for pioneering the use of directed evolution to engineer enzymes. Since January 2021, she serves as an external co-chair of President Joe Biden's Council of Advisors on Science and Technology (PCAST). Early life and education Arnold is the daughter of Josephine Inman (née Routheau) and nuclear physicist William Howard Arnold, and the granddaughter of Lieutenant General William Howard Arnold. She grew up in the Pittsburgh suburb of Edgewood, and the Pittsburgh neighborhoods of Shadyside and Squirrel Hill, graduating from the city's Taylor Allderdice High School in 1974. As a high schooler, she hitchhiked to Washington, D.C., to protest the Vietnam War and lived on her own, working as ...
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Indel
Indel is a molecular biology term for an insertion or deletion of bases in the genome of an organism. It is classified among small genetic variations, measuring from 1 to 10 000 base pairs in length, including insertion and deletion events that may be separated by many years, and may not be related to each other in any way. A microindel is defined as an indel that results in a net change of 1 to 50 nucleotides. In coding regions of the genome, unless the length of an indel is a multiple of 3, it will produce a frameshift mutation. For example, a common microindel which results in a frameshift causes Bloom syndrome in the Jewish or Japanese population. Indels can be contrasted with a point mutation. An indel inserts or deletes nucleotides from a sequence, while a point mutation is a form of substitution that ''replaces'' one of the nucleotides without changing the overall number in the DNA. Indels can also be contrasted with Tandem Base Mutations (TBM), which may result from fu ...
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Polymerase Chain Reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) to a large enough amount to study in detail. PCR was invented in 1983 by the American biochemist Kary Mullis at Cetus Corporation; Mullis and biochemist Michael Smith, who had developed other essential ways of manipulating DNA, were jointly awarded the Nobel Prize in Chemistry in 1993. PCR is fundamental to many of the procedures used in genetic testing and research, including analysis of ancient samples of DNA and identification of infectious agents. Using PCR, copies of very small amounts of DNA sequences are exponentially amplified in a series of cycles of temperature changes. PCR is now a common and often indispensable technique used in medical laboratory research for a broad variety of applications including biomedical resear ...
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Point Mutations
A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences that are moderately predictable based upon the specifics of the mutation. These consequences can range from no effect (e.g. synonymous mutations) to deleterious effects (e.g. frameshift mutations), with regard to protein production, composition, and function. Causes Point mutations usually take place during DNA replication. DNA replication occurs when one double-stranded DNA molecule creates two single strands of DNA, each of which is a template for the creation of the complementary strand. A single point mutation can change the whole DNA sequence. Changing one purine or pyrimidine may change the amino acid that the nucleotides code for. Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling ...
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Sequence Space
In functional analysis and related areas of mathematics, a sequence space is a vector space whose elements are infinite sequences of real or complex numbers. Equivalently, it is a function space whose elements are functions from the natural numbers to the field ''K'' of real or complex numbers. The set of all such functions is naturally identified with the set of all possible infinite sequences with elements in ''K'', and can be turned into a vector space under the operations of pointwise addition of functions and pointwise scalar multiplication. All sequence spaces are linear subspaces of this space. Sequence spaces are typically equipped with a norm, or at least the structure of a topological vector space. The most important sequence spaces in analysis are the spaces, consisting of the -power summable sequences, with the ''p''-norm. These are special cases of L''p'' spaces for the counting measure on the set of natural numbers. Other important classes of sequences ...
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How Random DNA Libraries Sample Sequence Space
How may refer to: * How (greeting), a word used in some misrepresentations of Native American/First Nations speech * How, an interrogative word in English grammar Art and entertainment Literature * ''How'' (book), a 2007 book by Dov Seidman * ''HOW'' (magazine), a magazine for graphic designers * H.O.W. Journal, an American art and literary journal Music * "How", a song by The Cranberries from ''Everybody Else Is Doing It, So Why Can't We?'' * "How", a song by Maroon 5 from ''Hands All Over'' * "How", a song by Regina Spektor from '' What We Saw from the Cheap Seats'' * "How", a song by Daughter from '' Not to Disappear'' * "How?" (song), by John Lennon Other media * HOW (graffiti artist), Raoul Perre, New York graffiti muralist * ''How'' (TV series), a British children's television show * ''How'' (video game), a platform game People * How (surname) * HOW (graffiti artist), Raoul Perre, New York graffiti muralist Places * How, Cumbria, England * How, Wisconsin, ...
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Heritability
Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of ''variation'' in a phenotypic trait in a population that is due to genetic variation between individuals in that population. The concept of heritability can be expressed in the form of the following question: "What is the proportion of the variation in a given trait within a population that is ''not'' explained by the environment or random chance?" Other causes of measured variation in a trait are characterized as environmental factors, including observational error. In human studies of heritability these are often apportioned into factors from "shared environment" and "non-shared environment" based on whether they tend to result in persons brought up in the same household being more or less similar to persons who were not. Heritability is estimated by comparing individual phenotypic variation among related individuals in a population, by examining the association between indiv ...
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Fitness (biology)
Fitness (often denoted w or ω in population genetics models) is the quantitative representation of individual reproductive success. It is also equal to the average contribution to the gene pool of the next generation, made by the same individuals of the specified genotype or phenotype. Fitness can be defined either with respect to a genotype or to a phenotype in a given environment or time. The fitness of a genotype is manifested through its phenotype, which is also affected by the developmental environment. The fitness of a given phenotype can also be different in different selective environments. With asexual reproduction, it is sufficient to assign fitnesses to genotypes. With sexual reproduction, recombination scrambles alleles into different genotypes every generation; in this case, fitness values can be assigned to alleles by averaging over possible genetic backgrounds. Natural selection tends to make alleles with higher fitness more common over time, resulting in ...
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Genetic Diversity
Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is distinguished from '' genetic variability'', which describes the tendency of genetic characteristics to vary. Genetic diversity serves as a way for populations to adapt to changing environments. With more variation, it is more likely that some individuals in a population will possess variations of alleles that are suited for the environment. Those individuals are more likely to survive to produce offspring bearing that allele. The population will continue for more generations because of the success of these individuals. The academic field of population genetics includes several hypotheses and theories regarding genetic diversity. The neutral theory of evolution proposes that diversity is the result of the accumulation of neutral substitutio ...
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