Misplaced Pages

#822177

84-550: A homeobox is a DNA sequence , around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism. Homeoboxes are found within genes that are involved in the regulation of patterns of anatomical development ( morphogenesis ) in animals , fungi , plants , and numerous single cell eukaryotes . Homeobox genes encode homeodomain protein products that are transcription factors sharing

168-521: A Holliday junction and requires both the phage protein Int and the bacterial protein IHF ( integration host factor ). Both Int and IHF bind to attP and form an intasome, a DNA-protein-complex designed for site-specific recombination of the phage and host DNA. The original B-O-B' sequence is changed by the integration to B-O-P'-phage DNA-P-O-B'. The phage DNA is now part of the host's genome. The classic induction of

252-429: A DNA sequence may be useful in practically any biological research . For example, in medicine it can be used to identify, diagnose and potentially develop treatments for genetic diseases . Similarly, research into pathogens may lead to treatments for contagious diseases. Biotechnology is a burgeoning discipline, with the potential for many useful products and services. RNA is not sequenced directly. Instead, it

336-423: A cell undergoing an SOS response will always be lysed, as no cI protein will be allowed to build up. However, the initial lytic/lysogenic decision on infection is also dependent on the cII and cIII proteins. In cells with sufficient nutrients, protease activity is high, which breaks down cII. This leads to the lytic lifestyle. In cells with limited nutrients, protease activity is low, making cII stable. This leads to

420-401: A cell will lyse or become a lysogen. Lambda phage has been used heavily as a model organism and has been an excellent tool first in microbial genetics , and then later in molecular genetics . Some of its uses include its application as a vector for the cloning of recombinant DNA ; the use of its site-specific recombinase (int) for the shuffling of cloned DNAs by the gateway method ; and

504-446: A characteristic protein fold structure that binds DNA to regulate expression of target genes. Homeodomain proteins regulate gene expression and cell differentiation during early embryonic development, thus mutations in homeobox genes can cause developmental disorders. Homeosis is a term coined by William Bateson to describe the outright replacement of a discrete body part with another body part, e.g. antennapedia —replacement of

588-466: A common eukaryotic ancestry for TALE and non-TALE homeodomain proteins. The Hox genes in humans are organized in four chromosomal clusters: ParaHox genes are analogously found in four areas. They include CDX1 , CDX2 , CDX4 ; GSX1 , GSX2 ; and PDX1 . Other genes considered Hox-like include EVX1 , EVX2 ; GBX1 , GBX2 ; MEOX1 , MEOX2 ; and MNX1 . The NK-like (NKL) genes, some of which are considered "MetaHox", are grouped with Hox-like genes into

672-427: A homeobox and a paired domain that also binds DNA to increase binding specificity, though some Pax genes have lost all or part of the homeobox sequence. Pax genes function in embryo segmentation , nervous system development, generation of the frontal eye fields , skeletal development, and formation of face structures. Pax 6 is a master regulator of eye development, such that the gene is necessary for development of

756-639: A large ANTP-like group. Humans have a "distal-less homeobox" family : DLX1 , DLX2 , DLX3 , DLX4 , DLX5 , and DLX6 . Dlx genes are involved in the development of the nervous system and of limbs. They are considered a subset of the NK-like genes. Human TALE (Three Amino acid Loop Extension) homeobox genes for an "atypical" homeodomain consist of 63 rather than 60 amino acids: IRX1 , IRX2 , IRX3 , IRX4 , IRX5 , IRX6 ; MEIS1 , MEIS2 , MEIS3 ; MKX ; PBX1 , PBX2 , PBX3 , PBX4 ; PKNOX1 , PKNOX2 ; TGIF1 , TGIF2 , TGIF2LX , TGIF2LY . In addition, humans have

840-475: A lysogen involved irradiating the infected cells with UV light. Any situation where a lysogen undergoes DNA damage or the SOS response of the host is otherwise stimulated leads to induction. Multiplicity reactivation (MR) is the process by which multiple viral genomes, each containing inactivating genome damage, interact within an infected cell to form a viable viral genome. MR was originally discovered with phage T4, but

924-451: A more posterior one. Famous examples are Antennapedia and bithorax in Drosophila , which can cause the development of legs instead of antennae and the development of a duplicated thorax, respectively. In vertebrates, the four paralog clusters are partially redundant in function, but have also acquired several derived functions. For example, HoxA and HoxD specify segment identity along

SECTION 10

#1732851519823

1008-517: A preference for the DNA sequence 5'-TAAT-3'; sequence-independent binding occurs with significantly lower affinity. The specificity of a single homeodomain protein is usually not enough to recognize specific target gene promoters, making cofactor binding an important mechanism for controlling binding sequence specificity and target gene expression. To achieve higher target specificity, homeodomain proteins form complexes with other transcription factors to recognize

1092-426: A recombinational repair process similar to that of MR. The repressor found in the phage lambda is a notable example of the level of control possible over gene expression by a very simple system. It forms a 'binary switch' with two genes under mutually exclusive expression, as discovered by Barbara J. Meyer . The lambda repressor gene system consists of (from left to right on the chromosome): The lambda repressor

1176-478: A rough measure of how conserved a particular region or sequence motif is among lineages. The absence of substitutions, or the presence of only very conservative substitutions (that is, the substitution of amino acids whose side chains have similar biochemical properties) in a particular region of the sequence, suggest that this region has structural or functional importance. Although DNA and RNA nucleotide bases are more similar to each other than are amino acids,

1260-425: A sequence is on the coding strand if it has the same order as the transcribed RNA. One sequence can be complementary to another sequence, meaning that they have the base on each position in the complementary (i.e., A to T, C to G) and in the reverse order. For example, the complementary sequence to TTAC is GTAA. If one strand of the double-stranded DNA is considered the sense strand, then the other strand, considered

1344-414: A sequence of amino acids making up a protein strand. Each group of three bases, called a codon , corresponds to a single amino acid, and there is a specific genetic code by which each possible combination of three bases corresponds to a specific amino acid. The central dogma of molecular biology outlines the mechanism by which proteins are constructed using information contained in nucleic acids. DNA

1428-418: A single ANTP-class homeobox gene. Gene duplication followed by neofunctionalization is responsible for the many homeobox genes found in eukaryotes. Comparison of homeobox genes and gene clusters has been used to understand the evolution of genome structure and body morphology throughout metazoans. Hox genes are the most commonly known subset of homeobox genes. They are essential metazoan genes that determine

1512-503: A so-called helix-turn-helix (HTH) structure, where the two alpha helices are connected by a short loop region. The N-terminal two helices of the homeodomain are antiparallel and the longer C-terminal helix is roughly perpendicular to the axes established by the first two. It is this third helix that interacts directly with DNA via a number of hydrogen bonds and hydrophobic interactions, as well as indirect interactions via water molecules, which occur between specific side chains and

1596-401: A special attachment site in the bacterial and phage genomes, called att . The sequence of the bacterial att site is called attB , between the gal and bio operons, and consists of the parts B-O-B', whereas the complementary sequence in the circular phage genome is called attP and consists of the parts P-O-P'. The integration itself is a sequential exchange (see genetic recombination ) via

1680-504: A stable minimum concentration of the repressor molecule and, should SOS signals arise, allows for more efficient prophage induction. An important distinction here is that between the two decisions; lysogeny and lysis on infection, and continuing lysogeny or lysis from a prophage. The latter is determined solely by the activation of RecA in the SOS response of the cell, as detailed in the section on induction. The former will also be affected by this;

1764-624: A thymine could occur in that position without impairing the sequence's functionality. These symbols are also valid for RNA, except with U (uracil) replacing T (thymine). Apart from adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U), DNA and RNA also contain bases that have been modified after the nucleic acid chain has been formed. In DNA, the most common modified base is 5-methylcytidine (m5C). In RNA, there are many modified bases, including pseudouridine (Ψ), dihydrouridine (D), inosine (I), ribothymidine (rT) and 7-methylguanosine (m7G). Hypoxanthine and xanthine are two of

SECTION 20

#1732851519823

1848-439: A variety of species contained the homeobox. Subsequent phylogenetic studies detailing the evolutionary relationship between homeobox-containing genes showed that these genes are present in all bilaterian animals. The characteristic homeodomain protein fold consists of a 60- amino acid long domain composed of three alpha helixes. The following shows the consensus homeodomain (~60 amino acid chain): Helix 2 and helix 3 form

1932-430: Is transcribed into mRNA molecules, which travel to the ribosome where the mRNA is used as a template for the construction of the protein strand. Since nucleic acids can bind to molecules with complementary sequences, there is a distinction between " sense " sequences which code for proteins, and the complementary "antisense" sequence, which is by itself nonfunctional, but can bind to the sense strand. DNA sequencing

2016-499: Is a bacterial virus, or bacteriophage , that infects the bacterial species Escherichia coli ( E. coli ). It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter

2100-446: Is a numerical sequence providing a quantitative measure of the local complexity of a DNA sequence, independently of the direction of processing. The manipulations of the information profiles enable the analysis of the sequences using alignment-free techniques, such as for example in motif and rearrangements detection. Lambda phage Enterobacteria phage λ ( lambda phage , coliphage λ , officially Escherichia virus Lambda )

2184-538: Is a self assembling dimer also known as the cI protein . It binds DNA in the helix-turn-helix binding motif. It regulates the transcription of the cI protein and the Cro protein. The life cycle of lambda phages is controlled by cI and Cro proteins. The lambda phage will remain in the lysogenic state if cI proteins predominate, but will be transformed into the lytic cycle if cro proteins predominate. The cI dimer may bind to any of three operators, O R 1, O R 2, and O R 3, in

2268-415: Is believed to contain around 20,000–25,000 genes. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases , or mutant forms of genes associated with increased risk of developing genetic disorders. Genetic testing identifies changes in chromosomes, genes, or proteins. Usually, testing

2352-443: Is copied to a DNA by reverse transcriptase , and this DNA is then sequenced. Current sequencing methods rely on the discriminatory ability of DNA polymerases, and therefore can only distinguish four bases. An inosine (created from adenosine during RNA editing ) is read as a G, and 5-methyl-cytosine (created from cytosine by DNA methylation ) is read as a C. With current technology, it is difficult to sequence small amounts of DNA, as

2436-403: Is due to RNA polymerase attaching to pL promoter site instead of the pR promotor site. Leftward transcription results in bar I and bar II transcription on the left operon. Bar positive phenotype is present when the rap gene is absent. The lack of growth of lambda phage is believed to occur due to a temperature sensitivity resulting in inhibition of growth. The lysogenic lifecycle begins once

2520-530: Is highly complex and involves reciprocal interactions, mostly inhibitory. Drosophila is known to use the polycomb and trithorax complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. Polycomb-group proteins can silence the Hox genes by modulation of chromatin structure. Mutations to homeobox genes can produce easily visible phenotypic changes in body segment identity, such as

2604-542: Is no parallel concept of secondary or tertiary sequence. Nucleic acids consist of a chain of linked units called nucleotides. Each nucleotide consists of three subunits: a phosphate group and a sugar ( ribose in the case of RNA , deoxyribose in DNA ) make up the backbone of the nucleic acid strand, and attached to the sugar is one of a set of nucleobases . The nucleobases are important in base pairing of strands to form higher-level secondary and tertiary structures such as

Homeobox - Misplaced Pages Continue

2688-437: Is qualitatively related to the sequences' evolutionary distance from one another. Roughly speaking, high sequence identity suggests that the sequences in question have a comparatively young most recent common ancestor , while low identity suggests that the divergence is more ancient. This approximation, which reflects the " molecular clock " hypothesis that a roughly constant rate of evolutionary change can be used to extrapolate

2772-405: Is the process of determining the nucleotide sequence of a given DNA fragment. The sequence of the DNA of a living thing encodes the necessary information for that living thing to survive and reproduce. Therefore, determining the sequence is useful in fundamental research into why and how organisms live, as well as in applied subjects. Because of the importance of DNA to living things, knowledge of

2856-548: Is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed. In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA , RNA , or protein to identify regions of similarity that may be due to functional, structural , or evolutionary relationships between

2940-453: The Cnidaria since before the earliest true Bilatera , making these genes pre- Paleozoic . It is accepted that the three major animal ANTP-class clusters, Hox, ParaHox, and NK (MetaHox), are the result of segmental duplications. A first duplication created MetaHox and ProtoHox, the latter of which later duplicated into Hox and ParaHox. The clusters themselves were created by tandem duplications of

3024-435: The O , P and Q genes. O and P are responsible for initiating replication, and Q is another antiterminator that allows the expression of head, tail, and lysis genes from P R’ . Pr is the promoter for rightward transcription, and the cro gene is a regulator gene. The cro gene will encode for the Cro protein that will then repress Prm promoter.  Once Pr transcription is underway the Q gene will then be transcribed at

3108-420: The gam, xis , bar and int genes. Gam proteins are involved in recombination. Gam is also important in that it inhibits the host RecBCD nuclease from degrading the 3’ ends in rolling circle replication. Int and xis are integration and excision proteins vital to lysogeny. Leftward transcription is believed to result in a deletion mutation of the rap gene resulting in a lack of growth of lambda phage. This

3192-574: The limb axis. Specific members of the Hox family have been implicated in vascular remodeling, angiogenesis , and disease by orchestrating changes in matrix degradation, integrins, and components of the ECM. HoxA5 is implicated in atherosclerosis. HoxD3 and HoxB3 are proinvasive, angiogenic genes that upregulate b3 and a5 integrins and Efna1 in ECs, respectively. HoxA3 induces endothelial cell (EC) migration by upregulating MMP14 and uPAR. Conversely, HoxD10 and HoxA5 have

3276-501: The promoter region of a specific target gene. Homeodomain proteins function as transcription factors due to the DNA binding properties of the conserved HTH motif. Homeodomain proteins are considered to be master control genes, meaning that a single protein can regulate expression of many target genes. Homeodomain proteins direct the formation of the body axes and body structures during early embryonic development . Many homeodomain proteins induce cellular differentiation by initiating

3360-619: The "homeobox". The existence of additional Drosophila genes containing the antennapedia homeobox sequence was independently reported by Ernst Hafen, Michael Levine , William McGinnis , and Walter Jakob Gehring of the University of Basel in Switzerland and Matthew P. Scott and Amy Weiner of Indiana University in Bloomington in 1984. Isolation of homologous genes by Edward de Robertis and William McGinnis revealed that numerous genes from

3444-589: The "sticky ends" of what is called the cos site. The cos site circularizes the DNA in the host cytoplasm. In its circular form, the phage genome, therefore, is 48,502 base pairs in length. The lambda genome can be inserted into the E. coli chromosome and is then called a prophage. See section below for details. The tail of lambda phages is made of at least 6 proteins (H, J, U, V, Stf, Tfa) and requires 7 more for assembly (I, K, L, M, Z, G/T). This assembly process begins with protein J, which then recruits proteins I, L, K, and G/T to add protein H. Once G and G/T leave

Homeobox - Misplaced Pages Continue

3528-546: The Antennapedia and Bithorax mutant phenotypes in Drosophila . Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution of segmented animals. Phylogenetic analysis of homeobox gene sequences and homeodomain protein structures suggests that the last common ancestor of plants, fungi, and animals had at least two homeobox genes. Molecular evidence shows that some limited number of Hox genes have existed in

3612-538: The C-terminal recognition helix aligning in the DNA's major groove and the unstructured peptide "tail" at the N-terminus aligning in the minor groove. The recognition helix and the inter-helix loops are rich in arginine and lysine residues, which form hydrogen bonds to the DNA backbone. Conserved hydrophobic residues in the center of the recognition helix aid in stabilizing the helix packing. Homeodomain proteins show

3696-402: The N protein interacting with the DNA; the protein instead binds to the freshly transcribed mRNA. Nut sites contain 3 conserved "boxes", of which only BoxB is essential. This is the lifecycle that the phage follows following most infections, where the cII protein does not reach a high enough concentration due to degradation, so does not activate its promoters. Rightward transcription expresses

3780-462: The additional resources available and with the more likely proximity of further infectable cells. A full biophysical model for lambda's lysis-lysogeny decision remains to be developed. Computer modeling and simulation suggest that random processes during infection drive the selection of lysis or lysogeny within individual cells. However, recent experiments suggest that physical differences among cells, that exist prior to infection, predetermine whether

3864-447: The antenna on the head of a fruit fly with legs. The "homeo-" prefix in the words "homeobox" and "homeodomain" stems from this mutational phenotype , which is observed when some of these genes are mutated in animals . The homeobox domain was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates . The existence of homeobox genes

3948-489: The antisense strand, will have the complementary sequence to the sense strand. While A, T, C, and G represent a particular nucleotide at a position, there are also letters that represent ambiguity which are used when more than one kind of nucleotide could occur at that position. The rules of the International Union of Pure and Applied Chemistry ( IUPAC ) are as follows: For example, W means that either an adenine or

4032-449: The application of its Red operon , including the proteins Red alpha (also called 'exo'), beta and gamma in the DNA engineering method called recombineering . The 48 kb DNA fragment of lambda phage is not essential for productive infection and can be replaced by foreign DNA, which can then be replicated by the phage. Lambda phage will enter bacteria more easily than plasmids, making it a useful vector that can either destroy or become part of

4116-438: The cI protein reaches a high enough concentration to activate its promoters, after a small number of infections. The prophage is duplicated with every subsequent cell division of the host. The phage genes expressed in this dormant state code for proteins that repress expression of other phage genes (such as the structural and lysis genes) in order to prevent entry into the lytic cycle. These repressive proteins are broken down when

4200-502: The cascades of coregulated genes required to produce individual tissues and organs . Other proteins in the family, such as NANOG are involved in maintaining pluripotency and preventing cell differentiation. Hox genes and their associated microRNAs are highly conserved developmental master regulators with tight tissue-specific, spatiotemporal control. These genes are known to be dysregulated in several cancers and are often controlled by DNA methylation. The regulation of Hox genes

4284-475: The complex, protein V can assemble onto the J/H scaffold. Then, protein U is added to the head-proximal end of the tail. Protein Z is able to connect the tail to the head. Protein H is cleaved due to the actions of proteins U and Z. Lambda phage is a non-contractile tailed phage, meaning during an infection event it cannot 'force' its DNA through a bacterial cell membrane. It must instead use an existing pathway to invade

SECTION 50

#1732851519823

4368-408: The conservation of base pairs can indicate a similar functional or structural role. Computational phylogenetics makes extensive use of sequence alignments in the construction and interpretation of phylogenetic trees , which are used to classify the evolutionary relationships between homologous genes represented in the genomes of divergent species. The degree to which sequences in a query set differ

4452-432: The cytoplasm of the bacterial cell. Usually, a " lytic cycle " ensues, where the lambda DNA is replicated and new phage particles are produced within the cell. This is followed by cell lysis , releasing the cell contents, including virions that have been assembled, into the environment. However, under certain conditions, the phage DNA may integrate itself into the host cell chromosome in the lysogenic pathway. In this state,

4536-484: The dimers will also bind to operators O L 1 and O L 2 (which are over 2 kb downstream from the R operators). When cI dimers are bound to O L 1, O L 2, O R 1, and O R 2 a loop is induced in the DNA, allowing these dimers to bind together to form an octamer. This is a phenomenon called long-range cooperativity . Upon formation of the octamer, cI dimers may cooperatively bind to O L 3 and O R 3, repressing transcription of cI. This autonegative regulation ensures

4620-399: The elapsed time since two genes first diverged (that is, the coalescence time), assumes that the effects of mutation and selection are constant across sequence lineages. Therefore, it does not account for possible differences among organisms or species in the rates of DNA repair or the possible functional conservation of specific regions in a sequence. (In the case of nucleotide sequences,

4704-549: The exposed bases within the major groove of the DNA. Homeodomain proteins are found in eukaryotes . Through the HTH motif, they share limited sequence similarity and structural similarity to prokaryotic transcription factors, such as lambda phage proteins that alter the expression of genes in prokaryotes . The HTH motif shows some sequence similarity but a similar structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins , homeodomain proteins, etc.). One of

4788-429: The famed double helix . The possible letters are A , C , G , and T , representing the four nucleotide bases of a DNA strand – adenine , cytosine , guanine , thymine – covalently linked to a phosphodiester backbone. In the typical case, the sequences are printed abutting one another without gaps, as in the sequence AAAGTCTGAC, read left to right in the 5' to 3' direction. With regards to transcription ,

4872-451: The far end of the operon for rightward transcription. The Q gene is a regulator gene found on this operon, which will control the expression of later genes for rightward transcription. Once the gene's regulatory proteins allow for expression, the Q protein will then act as an anti-terminator. This will then allow for the rest of the operon to be read through until it reaches the transcription terminator. Thus allowing expression of later genes in

4956-400: The following homeobox genes and proteins: Nucleic acid sequence The sequence represents genetic information . Biological deoxyribonucleic acid represents the information which directs the functions of an organism . Nucleic acids also have a secondary structure and tertiary structure . Primary structure is sometimes mistakenly referred to as "primary sequence". However there

5040-412: The host cell is under stress, resulting in the expression of the repressed phage genes. Stress can be from starvation , poisons (like antibiotics ), or other factors that can damage or destroy the host. In response to stress, the activated prophage is excised from the DNA of the host cell by one of the newly expressed gene products and enters its lytic pathway. The integration of phage λ takes place at

5124-485: The host cell, having evolved the tip of its tail to interact with a specific pore to allow entry of its DNA to the hosts. On initial infection, the stability of cII determines the lifestyle of the phage; stable cII will lead to the lysogenic pathway, whereas if cII is degraded the phage will go into the lytic pathway. Low temperature, starvation of the cells and high multiplicity of infection (MOI) are known to favor lysogeny (see later discussion). This occurs without

SECTION 60

#1732851519823

5208-454: The identity of embryonic regions along the anterior-posterior axis. The first vertebrate Hox gene was isolated in Xenopus by Edward De Robertis and colleagues in 1984. The main interest in this set of genes stems from their unique behavior and arrangement in the genome. Hox genes are typically found in an organized cluster. The linear order of Hox genes within a cluster is directly correlated to

5292-499: The initial letters of the names of three proteins where the characteristic domain was first identified) encode two 60 amino acid cysteine and histidine-rich LIM domains and a homeodomain. The LIM domains function in protein-protein interactions and can bind zinc molecules. LIM domain proteins are found in both the cytosol and the nucleus. They function in cytoskeletal remodeling, at focal adhesion sites, as scaffolds for protein complexes, and as transcription factors. Most Pax genes contain

5376-428: The lysogenic lifestyle. cIII appears to stabilize cII, both directly and by acting as a competitive inhibitor to the relevant proteases. This means that a cell "in trouble", i.e. lacking in nutrients and in a more dormant state, is more likely to lysogenise. This would be selected for because the phage can now lie dormant in the bacterium until it falls on better times, and so the phage can create more copies of itself with

5460-408: The lytic cycle after superinfecting an already lysogenized cell. The phage particle consists of a head (also known as a capsid ), a tail, and tail fibers (see image of virus below). The head contains the phage's double-strand linear DNA genome. During infections, the phage particle recognizes and binds to its host, E. coli , causing DNA in the head of the phage to be ejected through the tail into

5544-419: The many bases created through mutagen presence, both of them through deamination (replacement of the amine-group with a carbonyl-group). Hypoxanthine is produced from adenine , and xanthine is produced from guanine . Similarly, deamination of cytosine results in uracil . Given the two 10-nucleotide sequences, line them up and compare the differences between them. Calculate the percent difference by taking

5628-467: The molecular clock hypothesis in its most basic form also discounts the difference in acceptance rates between silent mutations that do not alter the meaning of a given codon and other mutations that result in a different amino acid being incorporated into the protein.) More statistically accurate methods allow the evolutionary rate on each branch of the phylogenetic tree to vary, thus producing better estimates of coalescence times for genes. Frequently

5712-415: The number of differences between the DNA bases divided by the total number of nucleotides. In this case there are three differences in the 10 nucleotide sequence. Thus there is a 30% difference. In biological systems, nucleic acids contain information which is used by a living cell to construct specific proteins . The sequence of nucleobases on a nucleic acid strand is translated by cell machinery into

5796-457: The operon, and leading to the expression of the lytic cycle. Pr promoter has been found to activate the origin in the use of rightward transcription, but the whole picture of this is still somewhat misunderstood. Given there are some caveats to this, for instance this process is different for other phages such as N15 phage, which may encode for DNA polymerase. Another example is the P22 phage may replace

5880-703: The opposite effect of suppressing EC migration and angiogenesis, and stabilizing adherens junctions by upregulating TIMP1/downregulating uPAR and MMP14, and by upregulating Tsp2/downregulating VEGFR2, Efna1, Hif1alpha and COX-2, respectively. HoxA5 also upregulates the tumor suppressor p53 and Akt1 by downregulation of PTEN. Suppression of HoxA5 has been shown to attenuate hemangioma growth. HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines. HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFalpha-inducible monocyte binding to HUVECs. LIM genes (named after

5964-750: The optic vesicle and subsequent eye structures. Proteins containing a POU region consist of a homeodomain and a separate, structurally homologous POU domain that contains two helix-turn-helix motifs and also binds DNA. The two domains are linked by a flexible loop that is long enough to stretch around the DNA helix, allowing the two domains to bind on opposite sides of the target DNA, collectively covering an eight-base segment with consensus sequence 5'-ATGCAAAT-3'. The individual domains of POU proteins bind DNA only weakly, but have strong sequence-specific affinity when linked. The POU domain itself has significant structural similarity with repressors expressed in bacteriophages , particularly lambda phage . As in animals,

6048-401: The order O R 1 > O R 2 > O R 3. Binding of a cI dimer to O R 1 enhances binding of a second cI dimer to O R 2, an effect called cooperativity . Thus, O R 1 and O R 2 are almost always simultaneously occupied by cI. However, this does not increase the affinity between cI and O R 3, which will be occupied only when the cI concentration is high. At high concentrations of cI,

6132-406: The order they are expressed in both time and space during development. This phenomenon is called colinearity. Mutations in these homeotic genes cause displacement of body segments during embryonic development. This is called ectopia . For example, when one gene is lost the segment develops into a more anterior one, while a mutation that leads to a gain of function causes a segment to develop into

6216-456: The p gene, which encodes for an essential replication protein for something that is capable of encoding for a DnaB helices. Q is similar to N in its effect: Q binds to RNA polymerase in Qut sites and the resulting complex can ignore terminators, however the mechanism is very different; the Q protein first associates with a DNA sequence rather than an mRNA sequence. Leftward transcription expresses

6300-418: The phage head. However, it is still not entirely clear whether the L and M proteins are part of the virion. All characterized lambdoid phages possess an N protein-mediated transcription antitermination mechanism, with the exception of phage HK022. The genome contains 48,502 base pairs of double-stranded, linear DNA, with 12-base single-strand segments at both 5' ends. These two single-stranded segments are

6384-515: The plant homeobox genes code for the typical 60 amino acid long DNA-binding homeodomain or in case of the TALE (three amino acid loop extension) homeobox genes for an atypical homeodomain consisting of 63 amino acids. According to their conserved intron–exon structure and to unique codomain architectures they have been grouped into 14 distinct classes: HD-ZIP I to IV, BEL, KNOX, PLINC, WOX, PHD, DDT, NDX, LD, SAWADEE and PINTOX. Conservation of codomains suggests

6468-649: The primary structure encodes motifs that are of functional importance. Some examples of sequence motifs are: the C/D and H/ACA boxes of snoRNAs , Sm binding site found in spliceosomal RNAs such as U1 , U2 , U4 , U5 , U6 , U12 and U3 , the Shine-Dalgarno sequence , the Kozak consensus sequence and the RNA polymerase III terminator . In bioinformatics , a sequence entropy, also known as sequence complexity or information profile,

6552-466: The principal differences between HTH motifs in these different proteins arises from the stereochemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, whereas for many of the homeotic and other DNA-binding proteins the requirement is relaxed. Homeodomains can bind both specifically and nonspecifically to B-DNA with

6636-421: The sequences. If two sequences in an alignment share a common ancestor, mismatches can be interpreted as point mutations and gaps as insertion or deletion mutations ( indels ) introduced in one or both lineages in the time since they diverged from one another. In sequence alignments of proteins, the degree of similarity between amino acids occupying a particular position in the sequence can be interpreted as

6720-485: The signal is too weak to measure. This is overcome by polymerase chain reaction (PCR) amplification. Once a nucleic acid sequence has been obtained from an organism, it is stored in silico in digital format. Digital genetic sequences may be stored in sequence databases , be analyzed (see Sequence analysis below), be digitally altered and be used as templates for creating new actual DNA using artificial gene synthesis . Digital genetic sequences may be analyzed using

6804-424: The tools of bioinformatics to attempt to determine its function. The DNA in an organism's genome can be analyzed to diagnose vulnerabilities to inherited diseases , and can also be used to determine a child's paternity (genetic father) or a person's ancestry . Normally, every person carries two variations of every gene , one inherited from their mother, the other inherited from their father. The human genome

6888-469: The λ DNA is called a prophage and stays resident within the host's genome without apparent harm to the host. The host is termed a lysogen when a prophage is present. This prophage may enter the lytic cycle when the lysogen enters a stressed condition. The virus particle consists of a head and a tail that can have tail fibers. The whole particle consists of 12–14 different proteins with more than 1000 protein molecules total and one DNA molecule located in

6972-462: Was first discovered in Drosophila by isolating the gene responsible for a homeotic transformation where legs grow from the head instead of the expected antennae. Walter Gehring identified a gene called antennapedia that caused this homeotic phenotype. Analysis of antennapedia revealed that this gene contained a 180 base pair sequence that encoded a DNA binding domain, which William McGinnis termed

7056-494: Was subsequently found in phage λ (as well as in numerous other bacterial and mammalian viruses ). MR of phage λ inactivated by UV light depends on the recombination function of either the host or of the infecting phage. Absence of both recombination systems leads to a loss of MR. Survival of UV-irradiated phage λ is increased when the E. coli host is lysogenic for an homologous prophage, a phenomenon termed prophage reactivation. Prophage reactivation in phage λ appears to occur by

#822177