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In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.
A transposable element is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces.
Insertion element is a short DNA sequence that acts as a simple transposable element. Insertion sequences have two major characteristics: they are small relative to other transposable elements and only code for proteins implicated in the transposition activity. These proteins are usually the transposase which catalyses the enzymatic reaction allowing the IS to move, and also one regulatory protein which either stimulates or inhibits the transposition activity. The coding region in an insertion sequence is usually flanked by inverted repeats. For example, the well-known IS911 is flanked by two 36bp inverted repeat extremities and the coding region has two genes partially overlapping orfA and orfAB, coding the transposase (OrfAB) and a regulatory protein (OrfA). A particular insertion sequence may be named according to the form ISn, where n is a number ; this is not the only naming scheme used, however. Although insertion sequences are usually discussed in the context of prokaryotic genomes, certain eukaryotic DNA sequences belonging to the family of Tc1/mariner transposable elements may be considered to be, insertion sequences.
Mobile genetic elements (MGEs) sometimes called selfish genetic elements are a type of genetic material that can move around within a genome, or that can be transferred from one species or replicon to another. MGEs are found in all organisms. In humans, approximately 50% of the genome is thought to be MGEs. MGEs play a distinct role in evolution. Gene duplication events can also happen through the mechanism of MGEs. MGEs can also cause mutations in protein coding regions, which alters the protein functions. These mechanisms can also rearrange genes in the host genome generating variation. These mechanism can increase fitness by gaining new or additional functions. An example of MGEs in evolutionary context are that virulence factors and antibiotic resistance genes of MGEs can be transported to share genetic code with neighboring bacteria. However, MGEs can also decrease fitness by introducing disease-causing alleles or mutations. The set of MGEs in an organism is called a mobilome, which is composed of a large number of plasmids, transposons and viruses.
Allan McCulloch Campbell was an American microbiologist and geneticist and the Barbara Kimball Browning Professor Emeritus in the Department of Biology at Stanford University. His pioneering work on Lambda phage helped to advance molecular biology in the late 20th century. An important collaborator and member of his laboratory at Stanford University was biochemist Alice del Campillo Campbell, his wife.
James Alan Shapiro is an American biologist, an expert in bacterial genetics and a professor in the Department of Biochemistry and Molecular Biology at the University of Chicago.
Gerald Mayer Rubin is an American biologist, notable for pioneering the use of transposable P elements in genetics, and for leading the public project to sequence the Drosophila melanogaster genome. Related to his genomics work, Rubin's lab is notable for development of genetic and genomics tools and studies of signal transduction and gene regulation. Rubin also serves as a vice president of the Howard Hughes Medical Institute and executive director of the Janelia Research Campus.
Transposon mutagenesis, or transposition mutagenesis, is a biological process that allows genes to be transferred to a host organism's chromosome, interrupting or modifying the function of an extant gene on the chromosome and causing mutation. Transposon mutagenesis is much more effective than chemical mutagenesis, with a higher mutation frequency and a lower chance of killing the organism. Other advantages include being able to induce single hit mutations, being able to incorporate selectable markers in strain construction, and being able to recover genes after mutagenesis. Disadvantages include the low frequency of transposition in living systems, and the inaccuracy of most transposition systems.
Allan C. Spradling is an American scientist and principal investigator at the Carnegie Institution for Science and the Howard Hughes Medical Institute who studies egg development in the model organism, Drosophila melanogaster, a fruit fly. He is considered a leading researcher in the developmental genetics of the fruit fly egg and has developed a number of techniques in his career that have led to greater understanding of fruit fly genetics including contributions to sequencing its genome. He is also an adjunct professor at Johns Hopkins University and at the Johns Hopkins University School of Medicine.
Transposons are semi-parasitic DNA sequences which can replicate and spread through the host's genome. They can be harnessed as a genetic tool for analysis of gene and protein function. The use of transposons is well-developed in Drosophila and in Thale cress and bacteria such as Escherichia coli.
The PiggyBac (PB) transposon is a mobile genetic element that efficiently transposes between vectors and chromosomes via a "cut and paste" mechanism. During transposition, the PB transposase recognizes transposon-specific inverted terminal repeat sequences (ITRs) located on both ends of the transposon vector and efficiently moves the contents from the original sites and integrates them into TTAA chromosomal sites. The powerful activity of the PiggyBac transposon system enables genes of interest between the two ITRs in the PB vector to be easily mobilized into target genomes. The TTAA-specific transposon piggyBac is rapidly becoming a highly useful transposon for genetic engineering of a wide variety of species, particularly insects. They were discovered in 1989 by Malcolm Fraser at the University of Notre Dame.
Tania A. Baker is an American biochemist who is a Professor of Biology at the Massachusetts Institute of Technology and formally the head of the Department of Biology. She earned her B.S. in Biochemistry from University of Wisconsin–Madison and her Ph.D. in Biochemistry from Stanford University under the guidance of Arthur Kornberg. She joined the MIT faculty in 1992 and her research is focused on the mechanisms and regulation of DNA transposition and protein chaperones. She is a member of the National Academy of Sciences, fellow of the American Academy of Arts and Sciences, and has been a Howard Hughes Medical Institute (HHMI) investigator since 1994.
Transposition is the process by which a specific genetic sequence, known as a transposon, is moved from one location of the genome to another. Simple, or conservative transposition, is a non-replicative mode of transposition. That is, in conservative transposition the transposon is completely removed from the genome and reintegrated into a new, non-homologous locus, the same genetic sequence is conserved throughout the entire process. The site in which the transposon is reintegrated into the genome is called the target site. A target site can be in the same chromosome as the transposon or within a different chromosome. Conservative transposition uses the "cut-and-paste" mechanism driven by the catalytic activity of the enzyme transposase. Transposase acts like DNA scissors; it is an enzyme that cuts through double-stranded DNA to remove the transposon, then transfers and pastes it into a target site.
Mary-Lou Pardue is an American geneticist who is a professor emerita in the Department of Biology at the Massachusetts Institute of Technology, which she originally joined in 1972. Her research focused on the role of telomeres in chromosome replication, particularly in Drosophila.
DNA transposons are DNA sequences, sometimes referred to "jumping genes", that can move and integrate to different locations within the genome. They are class II transposable elements (TEs) that move through a DNA intermediate, as opposed to class I TEs, retrotransposons, that move through an RNA intermediate. DNA transposons can move in the DNA of an organism via a single-or double-stranded DNA intermediate. DNA transposons have been found in both prokaryotic and eukaryotic organisms. They can make up a significant portion of an organism's genome, particularly in eukaryotes. In prokaryotes, TE's can facilitate the horizontal transfer of antibiotic resistance or other genes associated with virulence. After replicating and propagating in a host, all transposon copies become inactivated and are lost unless the transposon passes to a genome by starting a new life cycle with horizontal transfer. It is important to note that DNA transposons do not randomly insert themselves into the genome, but rather show preference for specific sites.
Nancy Kleckner is the Herchel Smith Professor of Molecular Biology at Harvard University and principal investigator at the Kleckner Laboratory at Harvard University.
Anna Marie (Ann) Skalka is an American virologist, molecular biologist and geneticist who is professor emeritus and senior advisor to the president at the Fox Chase Cancer Center. She is a co-author of a textbook on virology, Principles of Virology.
hAT transposons are a superfamily of DNA transposons, or Class II transposable elements, that are common in the genomes of plants, animals, and fungi.
Integrative and conjugative elements (ICEs) are mobile genetic elements present in both gram-positive and gram-negative bacteria. In a donor cell, ICEs are located primarily on the chromosome, but have the ability to excise themselves from the genome and transfer to recipient cells via bacterial conjugation.
CRISPR-associated transposons or CASTs are mobile genetic elements (MGEs) that have evolved to make use of minimal CRISPR systems for RNA-guided transposition of their DNA. Unlike traditional CRISPR systems that contain interference mechanisms to degrade targeted DNA, CASTs lack proteins and/or protein domains responsible for DNA cleavage. Specialized transposon machinery, similar to that of the well characterized Tn7 transposon, complexes with the CRISPR RNA (crRNA) and associated Cas proteins for transposition. CAST systems have been characterized in a wide range of bacteria and make use of variable CRISPR configurations including Type I-F, Type I-B, Type I-C, Type I-D, Type I-E, Type IV, and Type V-K. MGEs remain an important part of genetic exchange by horizontal gene transfer and CASTs have been implicated in the exchange of antibiotic resistance and antiviral defense mechanisms, as well as genes involved in central carbon metabolism. These systems show promise for genetic engineering due to their programmability, PAM flexibility, and ability to insert directly into the host genome without double strand breaks requiring activation of host repair mechanisms. They also lack Cas1 and Cas2 proteins and so rely on other more complete CRISPR systems for spacer acquisition in trans.
References
- 1 2 3 "Nancy Craig, Ph.D." Johns Hopkins University. Retrieved 4 September 2018.
- 1 2 3 4 5 6 Trivedi, B. P. (13 August 2012). "Profile of Nancy L. Craig". Proceedings of the National Academy of Sciences. 109 (36): 14283–14284. Bibcode:2012PNAS..10914283T. doi: 10.1073/pnas.1212357109 . PMC 3437901 . PMID 22891344.
- ↑ Nybo, Kristie (1 January 2014). "Profile of Nancy Craig". BioTechniques. 56 (1): 11. doi: 10.2144/000114120 .
- ↑ "Nancy L. Craig, Ph.D." Howard Hughes Medical Institute. Retrieved 4 September 2018.
- ↑ "Nancy Craig". National Academy of Sciences. Retrieved 4 September 2018.
- ↑ "Craig Lab Research". Johns Hopkins University. Retrieved 4 September 2018.
- ↑ "SalioGen Therapeutics Strengthens Management with Key Additions to Leadership Team to Advance Its Gene Coding Platform". 28 July 2021. Retrieved 8 February 2024.
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