6862
116-472: 20997 ENSG00000164458 ENSMUSG00000062327 O15178 P20293 NM_001270484 NM_003181 NM_001366285 NM_001366286 NM_009309 NP_001257413 NP_003172 NP_001353214 NP_001353215 NP_033335 T-box transcription factor T , also known as Brachyury protein , is encoded for in humans and other apes by the TBXT gene . Brachyury functions as a transcription factor within
232-588: A promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription. The recognition typically occurs as a consensus sequence like the TATA box . A gene can have more than one promoter, resulting in messenger RNAs ( mRNA ) that differ in how far they extend in the 5' end. Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at
348-639: A " start codon ", and three " stop codons " indicate the beginning and end of the protein coding region . There are 64 possible codons (four possible nucleotides at each of three positions, hence 4 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms. Xenopus laevis X. boiei Wagler 1827 The African clawed frog ( Xenopus laevis ), also known as simply xenopus , African clawed toad , African claw-toed frog or
464-523: A cell-free environment which allows easier manipulation. The first vertebrate ever to be cloned was an African clawed frog in 1962, an experiment for which Sir John Gurdon was awarded the Nobel Prize in Physiology or Medicine in 2012 "for the discovery that mature cells can be reprogrammed to become pluripotent". Additionally, four female African clawed frogs and stored sperm were present on
580-445: A continuous messenger RNA , referred to as a polycistronic mRNA . The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region , and represses transcription of
696-401: A definitive diagnostic marker, key driver and therapeutic target for chordoma , a rare malignant tumor that arises from remnant notochordal cells lodged in the vertebrae. The evidence regarding brachyury's role in chordoma includes: Brachyury is an important factor in promoting the epithelial–mesenchymal transition (EMT). Cells that over-express brachyury have down-regulated expression of
812-498: A double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile . The expression of genes encoded in DNA begins by transcribing the gene into RNA , a second type of nucleic acid that is very similar to DNA, but whose monomers contain
928-488: A few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer . Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas
1044-434: A gene - surprisingly, there is no definition that is entirely satisfactory. A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere. The important parts of such definitions are: (1) that
1160-573: A gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there's one other important part of the definition and it is emphasized in Kostas Kampourakis' book Making Sense of Genes . Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecules. With 'encoding information', I mean that
1276-410: A gene may be split across chromosomes but those transcripts are concatenated back together into a functional sequence by trans-splicing . It is also possible for overlapping genes to share some of their DNA sequence, either on opposite strands or the same strand (in a different reading frame, or even the same reading frame). In all organisms, two steps are required to read the information encoded in
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#17327646701641392-404: A gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA ( mRNA ). Second, that mRNA is translated to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression , and the resulting molecule
1508-578: A gene: that of bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. An automated version of the Sanger method was used in early phases of the Human Genome Project . The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called
1624-439: A gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence. The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome . DNA packaged and condensed in this way is called chromatin . The manner in which DNA
1740-459: A harmful invasive species. They can travel short distances to other bodies of water, and some have even been documented to survive mild freezes. They have been shown to devastate native populations of frogs and other creatures by eating their young. In 2003, Xenopus laevis frogs were discovered in a pond at San Francisco 's Golden Gate Park . Much debate now exists in the area on how to exterminate these creatures and keep them from spreading. It
1856-448: A high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently. Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters. Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act by binding to transcription factors which then cause
1972-541: A more comprehensive discussion of the use of these frogs in biomedical research, see Xenopus . Xenopus laevis is also notable for its use in the first widely used method of pregnancy testing . In the 1930s, two South African researchers, Hillel Shapiro and Harry Zwarenstein, students of Lancelot Hogben at the University of Cape Town , discovered that the urine from pregnant women would induce oocyte production in X. laevis within 8–12 hours of injection. This
2088-458: A more pronounced cloaca and have hip-like bulges above their rear legs where their eggs are internally located. Both males and females have a cloaca , which is a chamber through which digestive and urinary wastes pass and through which the reproductive systems also empty. The cloaca empties by way of the vent which in reptiles and amphibians is a single opening for all three systems. African clawed frogs are fully aquatic and will rarely leave
2204-516: A mottled greenish-grey-brown in color, sometimes with yellowish botches, and with a pale white-cream belly. African clawed frogs have been frequently sold as pets, and are sometimes misidentified as African dwarf frogs . Albino clawed frogs are common and sold as animals for laboratories . Amphibians reproduce by fertilizing eggs outside of the female's body (see frog reproduction ). Of the seven amplexus modes (positions in which frogs mate), these frogs are found breeding in inguinal amplexus, where
2320-572: A new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century. Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g. RNA viruses ), bacterial operons are multiple protein-coding regions transcribed into single large mRNAs, alternative splicing enables
2436-594: A part in EMT associated with benign disease such as renal fibrosis . Because brachyury is expressed in tumors but not in normal adult tissues it has been proposed as a potential drug target with applicability across tumor types. In particular, brachyury-specific peptides are presented on HLA receptors of cells in which it is expressed, representing a tumor specific antigen. Various therapeutic vaccines have been developed which are intended to stimulate an immune response to brachyury expressing cells. Gene In biology ,
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#17327646701642552-631: A permit in the following US states: Arizona, California, Kentucky, Louisiana, New Jersey, North Carolina, Oregon, Vermont, Virginia, Hawaii, Nevada, and Washington state. However, it is legal to own Xenopus laevis in New Brunswick (Canada) and Ohio. Feral colonies of Xenopus laevis exist in South Wales , United Kingdom . In Yunnan , China there is a population of albino clawed frogs in Lake Kunming , along with another invasive:
2668-400: A process known as RNA splicing . Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites , where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from
2784-419: A protein-coding gene consists of many elements of which the actual protein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA. All genes are associated with regulatory sequences that are required for their expression. First, genes require
2900-401: A result of the effect on TBXT's tail-encoding material that AluY has alongside AluSx1 , isoform TBXT-Δexon6 is created. Isoforms are often a result of mutation, polymorphism, and recombination, and happen to share often highly similar functions to the proteins they derive from. However often they can have some key differences due to either containing added instructions or missing instructions
3016-412: A single genomic region to encode multiple district products and trans-splicing concatenates mRNAs from shorter coding sequence across the genome. Since molecular definitions exclude elements such as introns, promotors, and other regulatory regions , these are instead thought of as "associated" with the gene and affect its function. An even broader operational definition is sometimes used to encompass
3132-531: A single letter gene symbol. Tbxt was cloned by Bernhard Herrmann and colleagues and proved to encode a 436 amino acid embryonic nuclear transcription factor . Tbxt binds to a specific DNA element, a near palindromic sequence TCACACCT through a region in its N-terminus, called the T-box. Tbxt is the founding member of the T-box family which in mammals currently consists of 18 T-box genes. The crystal structure of
3248-475: A strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along
3364-409: A true gene, by this definition, one has to prove that the transcript has a biological function. Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). This was based on the idea that the gene was the DNA that was directly responsible for production of
3480-452: Is a prognostic biomarker for HCC, and the gene may be a target for cancer treatments in the future. Research posits that there are some downsides that are more likely to occur in the embryonic stage due to the tailless mutation of TBXT-Δexon6. Exon 6's excision fundamentally affects the manner in which TBXT-encoded cells divide, distribute information, and form tissue because of how stem-loop sites create genetic instability . As such, it
3596-561: Is able to fit into their mouths. Being aquatic, clawed frogs use their sense of smell and their lateral line to detect prey rather than eyesight like other frogs. However, clawed frogs can still see using their eyes and will stalk prey or watch predators by sticking their heads out of the water. Clawed frogs will dig through substrate to unearth worms and other food. Unlike other frogs, they have no tongue to extend to catch food, so clawed frogs use their hands to grab food and shovel it into their mouths. These frogs are particularly cannibalistic;
T-box transcription factor T - Misplaced Pages Continue
3712-474: Is also associated with resistance to tamoxifen and to cytotoxic chemotherapy. In lung cancer, brachyury expression is associated with recurrence and decreased survival. It is also associated with resistance to cytotoxic chemotherapy, radiation, and EGFR kinase inhibitors. In prostate cancer, brachyury expression is associated with Gleason score, perineural, invasion and capsular invasion. In addition to its role in common cancers, brachyury has been identified as
3828-456: Is called a gene product . The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code . Sets of three nucleotides, known as codons , each correspond to a specific amino acid. The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4 (see Crick, Brenner et al. experiment ). Additionally,
3944-486: Is cited as being the protein that is primarily responsible for tail development in mammals. However, due to being a genetically-induced phenotype , it is possible for tail-encoding material to be effectively silenced by mutation . This is the mechanism by which the ntl ortholog developed in the hominidae taxa . In particular, an Alu element in TBXT is responsible for the taillessness ( ntl ) ortholog. An Alu element
4060-632: Is considered a more viable model for genetics, although gene editing protocols have now been perfected for. Roger Wolcott Sperry used X. laevis for his famous experiments describing the development of the visual system. These experiments led to the formulation of the chemoaffinity hypothesis . X. laevis have been used as a model organism in vertebrae cardiogenesis, human congenital heart defects, and in GWAS studies of congenital heart defects. Xenopus oocytes provide an important expression system for molecular biology . By injecting DNA or mRNA into
4176-436: Is evolved, mobile RNA that is exclusively in primates. These elements are capable of mobilizing around a genome, making Alu elements transposons . The Alu element that is observed to catalyze taillessness in TBXT is AluY . While normally Alu elements are not individually impactful, the presence of another Alu element active in TBXT, AluSx1 , is coded such that its nucleotides are the inverse of AluY ’s. Because of this,
4292-451: Is highly conserved among all mammals; however, a spontaneous vertebral and spinal dysplasia (VSD) mutation in this gene has been associated with the development of six or fewer cervical vertebrae instead of the usual seven. In mice, T is expressed in the inner cell mass of the blastocyst stage embryo (but not in the majority of mouse embryonic stem cells ) followed by the primitive streak (see image). In later development, expression
4408-413: Is implicated in the initiation and/or progression of a number of tumor types including chordoma, germ cell tumors , hemangioblastoma , GIST , lung cancer , small cell carcinoma of the lung, breast cancer , colon cancer , hepatocellular carcinoma , prostate cancer , and oral squamous carcinoma. In breast cancer, brachyury expression is associated with recurrence, metastasis and reduced survival. It
4524-503: Is known with certainty. Some experts hypothesize that taillessness contributes to a stronger, more upright stance. The stance observed by primates with a smaller lumbar is seen to be effective. Grounded mobility and maintaining balance in climbing are more feasible given the evenly distributed body weight observed in hominids. The presence of an additional appendage can also mean another appendage for predators to grab, and one that also consumes energy to move and takes up more space. Brachyury
4640-469: Is lethal at around embryonic day 10 due to defects in mesoderm formation, notochord differentiation and the absence of structures posterior to the forelimb bud (Dobrovolskaïa-Zavadskaïa, 1927). The name brachyury comes from the Greek brakhus meaning short and oura meaning tail. In 2018, HGNC updated the human gene name from T to TBXT , presumably to overcome difficulties associated with searching for
4756-481: Is localised to the node and notochord. In Xenopus laevis , Xbra (the Xenopus T homologue, also recently renamed t ) is expressed in the mesodermal marginal zone of the pre-gastrula embryo followed by localisation to the blastopore and notochord at the mid-gastrula stage. The Danio rerio ortholog is known as ntl (no tail). TBXT is a transcription factor observed in vertebrate organisms. As such, it
T-box transcription factor T - Misplaced Pages Continue
4872-400: Is nearly the same for all known organisms. The total complement of genes in an organism or cell is known as its genome , which may be stored on one or more chromosomes . A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. The region of the chromosome at which a particular gene is located is called its locus . Each locus contains one allele of
4988-444: Is primarily responsible for the genotype that codes for tail formation due to its observed role in axial development and the construction of posterior mesoderm within the lumbar and sacral regions. TBXT transcribes genes that form notochord cells, which are responsible for the flexibility, length, and balance of the spine, including tail vertebrae . Because of the role that the transcription factor plays in spinal development, it
5104-407: Is seen by experts that tail loss has contributed to the existence and frequency of developmental defects in the neural tube and sacral region . Primarily, spina bifida and sacral agenesis are the most likely suspects due to their direct relation to lumbar development . Spina bifida is an error in the build of the spinal neural tube, causing it to not fully close and leaving nerves exposed within
5220-403: Is still part of the definition of a gene in most textbooks. For example, The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of
5336-399: Is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression . In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins , telomeres , and
5452-486: Is unknown if these frogs entered the San Francisco ecosystem through intentional release or escape into the wild. San Francisco officials drained Lily Pond and fenced off the area to prevent the frogs from escaping to other ponds in the hopes they starve to death. Due to incidents in which these frogs were released and allowed to escape into the wild, African clawed frogs are illegal to own, transport or sell without
5568-493: The platanna ) is a species of African aquatic frog of the family Pipidae . Its name is derived from the short black claws on its feet. The word Xenopus means 'strange foot' and laevis means 'smooth'. The species is found throughout much of Sub-Saharan Africa ( Nigeria and Sudan to South Africa ), and in isolated, introduced populations in North America, South America, Europe, and Asia. All species of
5684-486: The American bullfrog . Because this population is albino, it suggests that the clawed frogs originated from the pet trade or a laboratory. The African clawed frog may be an important vector and the initial source of Batrachochytrium dendrobatidis , a chytrid fungus that has been implicated in the drastic decline in amphibian populations in many parts of the world. Unlike in many other amphibian species (including
5800-476: The Space Shuttle Endeavour when it was launched into space on mission STS-47 on September 12, 1992, so that scientists could test whether reproduction and development could occur normally in zero gravity. Xenopus laevis also serves as an ideal model system for the study of the mechanisms of apoptosis. In fact, iodine and thyroxine stimulate the spectacular apoptosis of the cells of
5916-415: The T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra . The brachyury mutation was first described in mice by Nadezhda Alexandrovna Dobrovolskaya-Zavadskaya in 1927 as a mutation that affected tail length and sacral vertebrae in heterozygous animals. In homozygous animals, the brachyury mutation
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#17327646701646032-511: The aging process. The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division . Prokaryotes ( bacteria and archaea ) typically store their genomes on a single, large, circular chromosome . Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes. Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids , which usually encode only
6148-459: The blastopore . It also defines the mesoderm during gastrulation. Tissue-culture based techniques have demonstrated one of its roles may be in controlling the velocity of cells as they leave the primitive streak. It effects transcription of genes required for mesoderm formation and cellular differentiation . Brachyury has also been shown to help establish the cervical vertebral blueprint during fetal development. The number of cervical vertebrae
6264-401: The central dogma of molecular biology , which states that proteins are translated from RNA , which is transcribed from DNA . This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses . The modern study of genetics at the level of DNA is known as molecular genetics . In 1972, Walter Fiers and his team were the first to determine the sequence of
6380-419: The centromere . Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication . The length of the telomeres decreases each time the genome is replicated and has been implicated in
6496-717: The mediobasal hypothalamus , then it stimulates seasonal testicular growth; if peripherally, then testicular regression and cold-season thermogenesis. These observations are regarded as widely applicable across vertebrate thyroid systems. The lipidomics of Xenopus oocytes have been studied by Tian et al 2014 and Phan et al 2015. In X. laevis , epigenetic methylation changes in neural-developmental genes associated with aging are analogous to aging related epigenetic changes in mammalian species. This finding suggests that, during their evolutionary divergence, patterns of epigenetic changes in neural-development genes during aging have been conserved between frogs and mammals C. In
6612-554: The modern synthesis , a term introduced by Julian Huxley . This view of evolution was emphasized by George C. Williams ' gene-centric view of evolution . He proposed that the Mendelian gene is a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." Related ideas emphasizing the centrality of Mendelian genes and the importance of natural selection in evolution were popularized by Richard Dawkins . The development of
6728-475: The neutral theory of evolution in the late 1960s led to the recognition that random genetic drift is a major player in evolution and that neutral theory should be the null hypothesis of molecular evolution. This led to the construction of phylogenetic trees and the development of the molecular clock , which is the basis of all dating techniques using DNA sequences. These techniques are not confined to molecular gene sequences but can be used on all DNA segments in
6844-481: The oocyte . Translation of proteins can be blocked or splicing of pre-mRNA can be modified by injection of Morpholino antisense oligos into the oocyte (for distribution throughout the embryo) or early embryo (for distribution only into daughter cells of the injected cell). Extracts from the eggs of X. laevis frogs are also commonly used for biochemical studies of DNA replication and repair, as these extracts fully support DNA replication and other related processes in
6960-750: The operon ; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon ). The products of operon genes typically have related functions and are involved in the same regulatory network . Though many genes have simple structures, as with much of biology, others can be quite complex or represent unusual edge-cases. Eukaryotic genes often have introns that are much larger than their exons, and those introns can even have other genes nested inside them . Associated enhancers may be many kilobase away, or even on entirely different chromosomes operating via physical contact between two chromosomes. A single gene can encode multiple different functional products by alternative splicing , and conversely
7076-508: The phenotype of the individual. Most biological traits occur under the combined influence of polygenes (a set of different genes) and gene–environment interactions . Some genetic traits are instantly visible, such as eye color or the number of limbs, others are not, such as blood type , the risk for specific diseases, or the thousands of basic biochemical processes that constitute life . A gene can acquire mutations in its sequence , leading to different variants, known as alleles , in
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#17327646701647192-449: The population . These alleles encode slightly different versions of a gene, which may cause different phenotypical traits. Genes evolve due to natural selection or survival of the fittest and genetic drift of the alleles. There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories,
7308-595: The spinal cord . Sacral agenesis, on the other hand, is a series of physical malformations in the hips that result from the omission of sacral matter during the developmental process. Because both of these developmental disorders result in the displacement of organs and other bodily mechanisms, they are both directly related to outright malfunction of the kidney, bladder, and nervous system. This can lead to higher likelihood of diseases related to their functionality or infrastructure, such as neurogenic bladder dysfunction or hydrocephalus . Overexpression of brachyury may play
7424-407: The 6th exon that codes in TBXT. In a stem-loop structure, genetic material trapped within the loop is recognized by transcription-coupled nucleotide excision repair (TC NER) proteins as damage due to RNA polymerase being ostensibly stalled at the neck of the loop. This is also how lesions are able to occur at all–the stalled transcription process serves as a beacon for TC NER proteins to ascertain
7540-404: The DNA helix that produces a functional RNA molecule constitutes a gene. We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of
7656-450: The DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function. The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as
7772-766: The DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes , RNA-binding proteins , miRNA , as well as terminator , and start and stop codons . In addition, most eukaryotic open reading frames contain untranslated introns , which are removed and exons , which are connected together in
7888-514: The Mendelian gene or the molecular gene. The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. This is the gene described in The Selfish Gene . More thorough discussions of this version of a gene can be found in the articles Genetics and Gene-centered view of evolution . The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics —
8004-568: The National Institutes of Health. The work rapidly expanded to include de novo reconstruction of X. laevis transcripts, in collaboration with groups around the world donating Illumina Hi-Seq RNA sequencing datasets. Genome sequencing by the Rokhsar and Harland groups (UC Berkeley) and by Taira and collaborators (University of Tokyo, Japan) gave a major boost to the project, which, with additional contributions from investigators in
8120-496: The Netherlands, Korea, Canada and Australia, led to publication of the genome sequence and its characterization in 2016. X. laevis oocytes are often used as an easy model for the artificially induced expression of transgenes . For example, they are commonly used when studying chloroquine resistance produced by specialized transporter mutants. Even so the foreign expression tissue may itself confer some alterations to
8236-433: The adenines of one strand are paired with the thymines of the other strand, and so on. Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose ; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end . The two strands of
8352-412: The adhesion molecule E-cadherin , which allows them to undergo EMT. This process is at least partially mediated by the transcription factors AKT and Snail. Overexpression of brachyury has been linked to hepatocellular carcinoma (HCC, also called malignant hepatoma), a common type of liver cancer. While brachyury is promoting EMT, it can also induce metastasis of HCC cells. Brachyury expression
8468-514: The closely related western clawed frog ) where this chytrid fungus causes the disease Chytridiomycosis , it does not appear to affect the African clawed frog, making it an effective carrier. Invasive: The African clawed frog is considered invasive by the Centre of Invasive biology from Stellenbosh University with this species even going as far as predating on other species. There has even been
8584-402: The complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. The existence of discrete inheritable units
8700-524: The distinction between a heterozygote and homozygote , and the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance , which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis , from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). Darwin used
8816-410: The early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA. Collectively, this body of research established
8932-510: The expression, and so findings may or may not be entirely identical to native expression: For example, iron has been found by Bakouh et al 2017 to be an important substrate for one such transporter in X. l. oocytes, but as of 2020 iron is merely presumptively involved in native expression of the same gene. Xenbase is the Model Organism Database (MOD) for both Xenopus laevis and Xenopus tropicalis . Xenbase hosts
9048-522: The fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a recent article in American Scientist. ... to truly assess the potential significance of de novo genes, we relied on
9164-427: The family Pipidae are tongueless, toothless and completely aquatic. They use their hands to shove food in their mouths and down their throats and a hyobranchial pump to draw or suck things in their mouth. Pipidae have powerful legs for swimming and lunging after food. They also use the claws on their feet to tear pieces of large food. They have no external eardrums, but instead subcutaneous cartilaginous disks that serve
9280-550: The full details and release information regarding the current v10 Xenopus laevis genome released in 2022. The clawed frog have been kept as pets and research subjects since as early as the 1950s. They are extremely hardy and long lived, having been known to live up to 20 or even 30 years in captivity. African clawed frogs are frequently mislabeled as African dwarf frogs in pet stores. Identifiable differences are: African clawed frogs are voracious predators and easily adapt to many habitats. For this reason, they can easily become
9396-413: The functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome). In spite of
9512-630: The gene that is described in terms of DNA sequence. There are many different definitions of this gene — some of which are misleading or incorrect. Very early work in the field that became molecular genetics suggested the concept that one gene makes one protein (originally 'one gene - one enzyme'). However, genes that produce repressor RNAs were proposed in the 1950s and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes. This idea of two kinds of genes
9628-421: The genome. The vast majority of organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar ( 2-deoxyribose ), a phosphate group, and one of the four bases adenine , cytosine , guanine , and thymine . Two chains of DNA twist around each other to form a DNA double helix with
9744-421: The genomes of complex multicellular organisms , including humans, contain an absolute majority of DNA without an identified function. This DNA has often been referred to as " junk DNA ". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome , about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer. The structure of
9860-632: The human brachyury protein was solved in 2017 by Opher Gileadi and colleagues at the Structural Genomics Consortium in Oxford. The gene brachyury appears to have a conserved role in defining the midline of a bilaterian organism, and thus the establishment of the anterior-posterior axis; this function is apparent in chordates and molluscs. Its ancestral role, or at least the role it plays in the Cnidaria, appears to be in defining
9976-477: The intermediate template for the synthesis of a protein. The transmission of genes to an organism's offspring , is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype , that is specific to every given individual, within the gene pool of the population of a given species . The genotype, along with environmental and developmental factors, ultimately determines
10092-687: The isoform's name. Other common examples of influential isoforms include those involved in AMP-induced protein kinase that insert phosphate groups into specific sites of the cell depending on the subunit. The first insertion of the AluY element occurred approximately 20-25 million years ago, with the earliest hominid ancestor known to exhibit this mutation being the Hominoidea family of apes. Taillessness has become an overwhelmingly dominant phenotype, such that it contributes to speciation . Over time,
10208-615: The larval gills, tail and fins in amphibians metamorphosis , and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog. Stem cells of this frog were used to create xenobots . Early work on sequencing of the X. laevis genome was started when the Wallingford and Marcotte labs obtained funding from the Texas Institute for Drug and Diagnostic Development (TI3D), in conjunction with projects funded by
10324-464: The location of the stem-loop. Once TBXT is cleaved, trapped nucleotides–including exon 6–are excised from the completed transcription process by the TC NER mechanisms. Because of the resulting excision of exon 6, information contained within the exon is, too, removed from transcription. Consequently, it is posited that the material stored in exon 6 is, in part, responsible for full hominid tail growth. As
10440-425: The male clasps the female in front of the female's back legs until eggs are laid, and the male fertilizes the egg mass with the release of sperm. African clawed frogs are highly adaptable and will lay their eggs whenever conditions allow it. During wet rainy seasons they will travel to other ponds or puddles of water to search for food and new ponds. During times of drought, the clawed frogs can burrow themselves into
10556-444: The male. This frog has smooth slippery skin which is multicolored on its back with blotches of olive gray or brown. The underside is creamy white with a yellow tinge. Male and female frogs can be easily distinguished through the following differences. Male frogs are small and slim, while females are larger and more rotund. Males have black patches on their hands and arms which aid in grabbing onto females during amplexus. Females have
10672-474: The mud, becoming dormant for up to a year. Xenopus laevis have been known to survive 15 or more years in the wild and 25–30 years in captivity. They shed their skin every season, and eat their own shed skin. Although lacking a vocal sac , the males make a mating call of alternating long and short trills, by contracting the intrinsic laryngeal muscles . Females also answer vocally, signaling either acceptance (a rapping sound) or rejection (slow ticking) of
10788-455: The mutation occurred more regularly due to the influence of natural selection and fixation to stabilize and expand its presence in the ape gene pool prior to the eventual speciation of homo sapiens . There are several potential reasons for why taillessness has become the standard phenotype in the Hominidae taxa that offset the genetically disadvantageous aspects of tail mitigation, but little
10904-413: The nucleus. Splicing, followed by CPA, generate the final mature mRNA , which encodes the protein or RNA product. Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have poly(A) tails. Many prokaryotic genes are organized into operons , with multiple protein-coding sequences that are transcribed as a unit. The genes in an operon are transcribed as
11020-444: The oocyte or developing embryo, scientists can study the protein products in a controlled system. This allows rapid functional expression of manipulated DNAs (or mRNA ). This is particularly useful in electrophysiology , where the ease of recording from the oocyte makes expression of membrane channels attractive. One challenge of oocyte work is eliminating native proteins that might confound results, such as membrane channels native to
11136-493: The original protein is known to possess. TBXT-Δexon6 falls into this category, as it is an isoform that lacks the ability to process the code that enables proper tail formation in TBXT-containing organisms. This is because exon 6's material that helps encode for tail formation is excised from the contents of the transcribed RNA. As a result, it is effectively missing in the isoform, and is thus the key factor in determining
11252-431: The phosphate–sugar backbone spiralling around the outside, and the bases pointing inward with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds , whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, be complementary , with their sequence of bases matching such that
11368-416: The same function. They use their sensitive fingers and sense of smell to find food. Pipidae are scavengers and will eat almost anything living, dying, or dead and any type of organic waste. It is considered an invasive species in several countries , including across Europe. These frogs are plentiful in ponds and rivers within the south-eastern portion of Sub-Saharan Africa. They are aquatic and are often
11484-751: The stomach contents of feral clawed frogs in California have revealed large amounts of the frog's larvae. Clawed frog larvae are filter feeders and collect nutrients from plankton, allowing adult frogs that consume the tadpoles to have access to these nutrients. This allows clawed frogs to survive in areas that have little to no other food sources. Clawed frogs are nocturnal and most reproductive activity and feeding occurs after dark. Male clawed frogs are very promiscuous and will grab onto other males and even other species of frogs. Male frogs that are grasped will make release calls and attempt to break free. If not feeding, clawed frogs will just sit motionless on top of
11600-467: The strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein. This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for
11716-590: The substrate or floating, legs splayed below, at the waters surface with their nostrils and eyes sticking out. The clawed frog liver responds to low temperatures by increasing production of type II iodothyronine deiodinase through increased food intake . This in turn spurs the thyroid to increase T 3 to increase body temperature . (This T 3 increase also induces germ cell apoptosis , mediated through genes left over from tadpole metamorphosis.) The effects of provocation of T hormone release are broadly differentiated by where it starts: If centrally, within
11832-461: The sugar ribose rather than deoxyribose . RNA also contains the base uracil in place of thymine . RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three- nucleotide sequences called codons , which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids . The genetic code
11948-561: The super short generation time , or genetic simplicity generally desired in genetic model organisms , it is an important model organism in developmental biology , cell biology , toxicology and neurobiology . X. laevis takes 1 to 2 years to reach sexual maturity and, like most of its genus, it is tetraploid . It does have a large and easily manipulated embryo , however. The ease of manipulation in amphibian embryos has given them an important place in historical and modern developmental biology. A related species, Xenopus tropicalis ,
12064-809: The term gemmule to describe hypothetical particles that would mix during reproduction. Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries , Carl Correns , and Erich von Tschermak , who (claimed to have) reached similar conclusions in their own research. Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis , in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" ( Pangens in German), after Darwin's 1868 pangenesis theory. Twenty years later, in 1909, Wilhelm Johannsen introduced
12180-436: The term gene , he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen 's distinction between genotype (the genetic material of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment , the distinction between dominant and recessive traits,
12296-412: The term "gene" (inspired by the ancient Greek : γόνος, gonos , meaning offspring and procreation) and, in 1906, William Bateson , that of " genetics " while Eduard Strasburger , among others, still used the term "pangene" for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA)
12412-402: The two elements are paired together in the replication process, leading up to the formation of a stem-loop structure and an alternative splicing event that fundamentally influences transcription . The structure isolates and positions codons held between the two Alu elements in a hairpin-esque loop that consequently cannot be paired or transcribed. The trapped material, most notably, includes
12528-676: The water except to migrate to new water bodies during droughts or other disturbances. Clawed frogs have powerful legs that help them move quickly both underwater and on land. Feral clawed frogs in South Wales have been found to travel up to 2 kilometres (1.2 mi) between locations. The feet of Xenopus species have three black claws on the last three digits. These claws are used to rip apart food and scratch predators. Clawed frogs are carnivores and will eat both living and dead prey including fish, tadpoles, crustaceans, annelids, arthropods, and more. Clawed frogs will try to consume anything that
12644-654: The wide breadth of Xenopus research stems from the additional fact that cell-free extracts made from Xenopus are a premier in vitro system for studies of fundamental aspects of cell and molecular biology. Thus, Xenopus is the only vertebrate model system that allows for high-throughput in vivo analyses of gene function and high-throughput biochemistry. Xenopus oocytes are a leading system in their own right for studies of various systems, including ion transport and channel physiology. Xanthos et al 2001 uses oocytes to uncover T-box expression earlier than previously found in vertebrates. Although X. laevis does not have
12760-555: The wild - Found at higher densities in artificial water bodies such as ponds, dams and irrigation canals, rather than in natural lagoons or streams or rivers. - There is no evidence of predation on native anurans, but rather on their own larvae. - They face predation from native birds. Cause of concerns from African clawed frogs - They are reaching both lower and higher altitudes than formerly estimated. - They are able to migrate overland to colonise other water bodies, causing ecological disruption and spreading diseases. X. laevis in
12876-472: The wild are commonly infected by various parasites , including monogeneans in the urinary bladder . Xenopus embryos and eggs are a popular model system for a wide variety of biological studies, in part because they have the potential to lay eggs throughout the year. This animal is widely used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms. For
12992-614: The wild, X. laevis are native to wetlands , ponds, and lakes across arid/semiarid regions of Sub-Saharan Africa . X. laevis and X. muelleri occur along the western boundary of the Great African Rift . The people of the sub-Saharan are generally very familiar with this frog, and some cultures use it as a source of protein, an aphrodisiac , or as fertility medicine . Two historic outbreaks of priapism have been linked to consumption of frog legs from frogs that ate insects containing cantharidin . African clawed frogs in
13108-472: The word gene has two meanings. The Mendelian gene is a basic unit of heredity . The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA . There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of RNA or protein from a gene), DNA is first copied into RNA . RNA can be directly functional or be
13224-450: Was first suggested by Gregor Mendel (1822–1884). From 1857 to 1864, in Brno , Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants , tracking distinct traits from parent to offspring. He described these mathematically as 2 combinations where n is the number of differing characteristics in the original peas. Although he did not use
13340-430: Was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography , which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication. In
13456-528: Was used as a simple and reliable test up through to the 1960s. In the late 1940s, Carlos Galli Mainini found in separate studies that male specimens of Xenopus and Bufo could be used to indicate pregnancy Today, commercially available hCG is injected into Xenopus males and females to induce mating behavior and to breed these frogs in captivity at any time of the year. Xenopus has long been an important tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals. However,
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