Reading frame shift

1 Apr

Reading frame shift

reading frame shift Certain mutagens (acridine dyes, for example) intercalate themselves between the strands of a DNA double helix. During subse- quent replication, the newly formed complementary strands may have a nucleotide added or subtracted. A cistron containing an additional base or missing a base will transcribe a messenger RNA with a reading frame shift. That is, during translation the message will be read properly up to the point of loss or addi- tion. Thereafter, since the message will continue to be read in triplets, all subsequent codons will specify the wrong amino acids (and some may signal chain termination). Contrast with in-frame mutation. See acridine orange, acriflavin, amino acid, nonsense mu- tation, proflavin, translation. reading mistake the incorrect placement of an amino acid in a polypeptide chain during protein synthesis. reads overlapping base sequences generated dur- ing shotgun sequencing (q.v.) from which stretches of contiguous sequences, or contigs are assembled.

readthrough 1. transcription beyond a normal ter- minator sequence in DNA, due to occasional failure of RNA polymerase to recognize the termination signal or due to the temporary dissociation of a ter- mination factor (such as rho in bacteria) from the terminator sequence. 2. translation beyond the chain-terminator (stop) codon of an mRNA, as oc- curs by a nonsense suppressor (q.v.) tRNA. An ex- ample of readthrough is found in the tobacco mosaic virus (q.v.). Here a 183 kd protein is formed that contains amino acids specified by ORFs 1 and 2. reannealing in molecular genetics, the pairing of single-stranded DNA molecules that have comple- mentary base sequences to form duplex molecules. Reannealing and annealing (q.v.) differ in that the DNA molecules in the first case are from the same source and in the second case from different sources. See Appendix C, 1960, Doty et al.; Alu family, mouse satellite DNA, reassociation kinetics, repetitious genes.

reassociation reannealing (q.v.). reassociation kinetics a technique that measures the rate of reassociation of complementary strands of DNA derived from a single source. The DNA un- der study is fragmented into pieces several hundred base pairs in length and then disassociated into single strands by heating. Subsequently, the temperature is lowered and the rate of reannealing (q.v.) is moni- tored. Reassociation of DNA is followed in the form of a cot curve, which plots the fraction of molecules that have reannealed against the log of cot. Cot val- ues are defined as C0 × t, where C0 is the initial con- centration of single-stranded DNA in moles of nu- cleotides per liter and t is the reannealing time in seconds. Typical cot curves are shown on page 375. DNAs reannealing at low cot values (10−4-10−1) are composed of highly repetitive sequences, DNAs re- annealing at cot values between 100 and 102 are moderately repetitive, and DNAs reannealing at higher cot values are nonrepetitive.

See Appendix C, 1968, Britten and Kohne; Alu family, delta T50H, mouse satellite DNA, repetitious DNA. reassortant virus a virion consisting of DNA from one virus and protein from another viral species; e.g., through genetic engineering, a hybrid virus has been made containing genes from the human influ- enza virus and capsid proteins that provoke immu- nity, but also containing avian influenza virus genes that slow the rate of viral replication. See phenotypic mixing, pseudovirion. recapitulation the theory first put forth by Ernst Haeckel that an individual during its development passes through stages resembling the adult forms of its successive ancestors. The concept is often stated “ontogeny recapitulates phylogeny” and is some- times referred to as the biogenetic law. RecA protein the product of the RecA locus of E. coli. The protein is of great antiquity, since it occurs in virtually all bacteria. The RecA monomer contains 352 amino acids. The monomers are packed to form a continuous right-handed spiral with six monomers per turn of the helix. The spiral filament contains a deep groove that can accommodate up to three strands of DNA.

The RecA protein is a DNA- dependent ATPase, and ATP is hydrolyzed during genetic recombination processes. See Appendix C, 1965, Clark; 1992, Story, Weber, and Steitz. receptor element See controlling elements. receptor-mediated endocytosis endocytosis that involves the binding of a ligand, such as vitellogenin (q.v.) to a plasma membrane receptor followed by the lateral movement of the ligand-receptor com- plex through the membrane toward a coated pit. The cytoskeleton of each coated pit is a basketlike network of hexagons and pentagons formed by the assembly of three-legged protein complexes called triskelions. Each triskelion is composed of three mol- ecules of clathrin, a 185-kilodalton protein, and three smaller polypeptides. Once a clathrin-coated pit contains a large number of ligand-receptor com- plexes, it invaginates further into the cytoplasm and eventually a small vesicle is pinched off the pit. This endocytotic vesicle is called a receptosome. Once the ligands have been internalized in a receptosome, the

recessive gene

Reassociation kinetics

For each of the DNA samples tested, the number of base pairs in the genome is indicated by an arrow on the logarithmic scale at the top of the graph. The poly-U + poly-A sample is a double helix of RNA, with one strand containing only A and the other strand only U. The mouse satellite DNA is a fraction of nuclear DNA in mouse cells that differs in its physical properties from the bulk of the DNA. The calf DNA represents only those sequences that are present in single copies per haploid genome. The denatured DNA samples were fragmented by mechanical shear to chain lengths of about 400 nucleotides and incubated at a temperature near 60°C. The fraction reassociated was measured by the decrease in UV absorption as double strands formed. 

receptor molecules are returned intact to the plasma membrane. receptor-mediated translocation a hypothesis concerning the translocation of nascent polypeptides across the endoplasmic reticulum membrane. As shown in the diagram on page 376, soon after the signal sequence peptide of the nascent chain emerges from the ribosome it is recognized by a spe- cific receptor called the signal recognition particle (SRP). The second component of the translocation process is the docking protein. It is bound to the sur- face of the ER membrane, and it serves as a receptor for the SRP. Since the SRP binds to both the dock- ing protein and the signal sequence of the protein being translated, it serves to bring the ribosome into the vicinity of the ER membrane. Subsequently, the ribosome binds to a ribosome receptor on the ER and the nascent polypeptide is threaded through a pore in the membrane and into the ER lumen. A pepti- dase then removes the signal peptide from the newly synthesized protein molecule. See Appendix C, 1975, Blobel and Dobberstein; 1991, Simon and Blobel; leader sequence peptide, signal hypothesis, signal rec- ognition particle, translation, translocon. receptors See cell-surface receptors, cellular signal transduction.

receptosome See receptor-mediated endocytosis. recessive complementarity See complementary genes. recessive gene in diploid organisms, a gene that is phenotypically manifest in the homozygous state but is masked in the presence of its dominant allele. Usually the dominant gene produces a functional product, while its recessive allele does not. There- fore, the normal phenotype is produced if the domi- nant allele is present (in one or two doses per nu- cleus), and the mutant phenotype appears only in the absence of the normal allele (i.e., when the re- cessive gene is homozygous). By extension, the terms dominant and recessive are used in the same sense for heterokaryons and merozygotes.

recessive lethal

Receptor-mediated translocation

The mRNA is moving from left to right in this diagram. recessive lethal an allele that kills the cell or or- ganism that is homozygous or hemizygous for it. See lethal mutation. reciprocal crosses crosses of the forms A O × B P and B O × A P, where the individuals symbolized by A and B differ in genotype or phenotype or both. Reciprocal crosses are employed to detect sex link- age, maternal inheritance, or cytoplasmic inheri- tance (all of which see). reciprocal genes complementary genes (q.v.). reciprocal hybrids hybrid offspring derived from reciprocal crosses of parents from different species. reciprocal recombination in the gametes of dihy- brids, the production of new linkage arrangements that are different from those of the maternal and paternal homologs. For example, if the nonallelic mutants a and b were present in the coupling con- figuration AB/ab, crossovers would generate the re- ciprocal recombinant gametes Ab and aB in equal numbers.

reciprocal translocation See translocation. rec− mutant a class of mutations characterized by defective recombination. Such mutants are also radi- ation-sensitive, which suggests that enzymes func- tioning during the naturally occurring breakage and rejoining characterizing meiotic crossing over may also repair damage caused by mutagens. recognition protein See cyclins. recoil energy the energy imparted to the posi- tively charged ion formed during the radioactive transmutation of an atom. A high-energy beta parti- cle is emitted concurrently.

recombinant 1. the new individuals or cells arising as the result of recombination. 2. recombinant DNA or a clone containing recombinant DNA. recombinant DNA a composite DNA molecule created in vitro by joining a foreign DNA with a vec- tor molecule. recombinant DNA technology techniques for joining DNA molecules in vitro and introducing them into living cells where they replicate.

These techniques make possible (1) the isolation of specific DNA segments from almost any organism and their amplification in order to obtain large quantities for molecular analysis, (2) the synthesis in a host organ- ism of large amounts of specific gene products that may be useful for medicine or industry, and (3) the study of gene structure-function relationships by in vitro mutagenesis of cloned DNAs. See Appendix C, 1972, Jackson, Symons, and Berg; 1973, Cohen et al.; 1974, Murray and Murray; 1975, Asilomar Con- ference, Benton and Davis; 1976, Efstratiadis et al., Kan et al.; 1977, Collins and Holm, Gilbert; 1978, Maniatis et al.; 1979, Goeddel et al.; 1980, Chakra- barty, Berg et al.; 1981, Wagner, Kemp and Hall; 1982, Eli Lilly; 1985, Smithies et al.; 1994, Whi- tham et al.; expression vectors, gene cloning. recombinant inbred (RI) lines inbred lines, each derived independently from an F2 generation pro- duced from crossing two unrelated, inbred, progeni- tor lines. Each RI line has a characteristic combina- tion of genes with a different pattern of alternative alleles at multiple loci.

This technique has been used in mice to fix chance recombinants in a homozygous state in a group of strains derived from two unre- lated but highly inbred progenitor strains. recombinant joint the edge of a heteroduplex re- gion where two recombining DNA molecules are connected. recombinant RNA technology techniques that unite foreign RNA molecules or splice different RNAs from the same species. For example, a heter- ologous RNA sequence can be constructed by liga-


tion of two or more different RNA molecules with T4 RNA ligase. See Appendix C, 1983, Miele, Mills and Kramer. recombination See genetic recombination. recombination activating genes (RAGs) in hu- mans the RAG-1 and RAG-2 genes are about 8 kb apart, and they have been mapped to 11p13. Mis- sense mutations in both RAGs have been shown to be the cause of hereditary immunodeficiency syn- dromes. See Rag-1 and RAG-2. recombination frequency the number of recom- binants divided by the total number of progeny. This frequency is used as a guide in assessing the relative distances between loci on a genetic map. See Morgan unit. recombination hotspot special regions on chro- mosomes where the frequency of meiotic crossing over is elevated. Such hotspots are likely to be initia- tion sites for recombination. In the human genome, recombination hot spots occur at 200 kb intervals, usually between genes. recombination mapping See linkage map. recombination nodules (RNs) electron dense structures seen in electron micrographs of synapto- nemal complexes (q.v.).

In Drosophila, since the number of RNs in mid pachytene oocytes is about the same as the number of chiasmata observed at diplonena, it is assumed that RNs participate in the exchange process. The mei-W68 mutation abolishes meiotic exchange in the oocytes of homozygotes, and it also suppresses the formation of RNs. The SPO11 gene of Saccharomyces cerevisiae is an ortho- log of mei W68. SPO11 encodes topoisomerase II, an enzyme that produces double-strand breaks in DNA. See Appendix C, 1975, Carpenter; centromeric coupling, topoisomerase. recombination repair formation of a normal DNA molecule by exchanging correct for incorrect seg- ments between two damaged molecules. recombination suppression See crossover suppres- sor.

recombinators any sequences of nucleotides that promote genetic recombination in their neighbor- hood. An example would be the chi sequence (q.v.) in the E. coli chromosome. recon the smallest unit of DNA capable of recom- bination (corresponding to an adjacent pair of nucle- otides in cis position). See Appendix C, 1955, Benzer. record of performance a record of an animal with respect to certain economically important character- istics. Such data are used by livestock breeders in the artificial selection and development of improved breeds. recurrence risk the risk that a genetic defect that has appeared once in a family will appear in a child born subsequently. recurrent parent backcross parent. red blood cell erythrocyte. See hemoglobin, sickle- cell anemia.

Red Queen hypothesis one of two major mathe- matical models concerning the likely evolutionary state of communities under conditions of constancy in the physical environment. Stationary models pre- dict that evolution would grind to a halt. The Red Queen hypothesis predicts that evolution would continue because (1) the most important compo- nent of the species environment is other species in the community, and (2) not all species will be at their local adaptive peaks, and hence are capable of further evolution even though the physical environ- ment has stabilized. Any evolutionary advance made by one species will, through a close network of inter- actions, represent a deterioration in the biotic envi- ronment of all other species in that same commu- nity.

Consequently, these other species become subject to selective pressures to achieve evolutionary advances of their own, simply to catch up. The name for this hypothesis is derived from the Red Queen in Through the Looking Glass, who said: “Now here, you see, it takes all the running you can do to keep in the same place.” See lag load, zero sum assumption. reductase an enzyme responsible for reduction in an oxidation-reduction reaction. reduction classically defined as the addition of hy- drogen or electrons. Most biological reductions in- volve hydrogenations, and hydrogen transfer reac- tions are usually mediated by NADPH. In cases involving electron transfer, cytochromes (q.v.) are reduced. See nicotinamide-adenine-dinucleotide phos- phate, oxidation. reduction divisions the division that halves the zygotic chromosome number. See Appendix C, 1883, van Beneden; 1887, Weismann; meiosis. reductionism a philosophy that each phenomenon in the natural world can be understood from a knowledge of its component parts. See mechanistic philosophy.

reductive evolution

reductive evolution a downsizing of the genome which often occurs in obligate intercellular parasites.

The deletion of a subset of genes or their conversion into pseudogenes is tolerated, because the host now supplies the products normally controlled by the dispensable genes. See leprosy bacterium, regressive evolution, Rickettsia prowazeki. redundant cistrons cistrons frequently repeated on a chromosome. Examples are the cistrons in the nucleolus organizer coding for the ribosomal RNA molecules. redundant code See degenerate code. redundant DNA See repetitious DNA. refractive index the ratio of the velocity of light in a vacuum to its velocity in a given substance. See phase contrast microscope. regeneration the process whereby a whole animal or part(s) of an animal is(are) reformed after being lost or damaged in a fully developed individual. The phenomenon of regeneration is typical of most plants but is restricted in animals primarily to less complex forms such as certain flatworms (planarians) or poly- ploid cnidarians (e.g., hydroids).

Among the more complex animals, regeneration of whole limbs or other body parts is much less common in a few groups such as salamanders (see axolotl), which can regrow limbs, tails, heart muscle, jaws, spinal cord, and so on. Crabs can regrow lost claws. Some lizards can regrow lost tails. In humans, regeneration is mainly limited to superficial wound healing, although a few human tissues can regenerate (e.g., blood, liver). See dedifferentiation. Compare with metamor- phosis. regression coefficient the rate change of the de- pendent variable with respect to the independent variable. The change in mutation frequency per unit change in radiation dose, for example, would be de- termined by the regression coefficient of the regres- sion line (q.v.). regression line a line that defines how much an increase or decrease in one factor may be expected from a unit increase in another. See line of best fit, scatter diagram. regressive evolution the reduction in morpholog- ical complexity as the result of the loss of unneeded structures or biochemical pathways. An example would be the loss of eyes and pigments by animals such as fish and crustaceans living in caves. See mito- somes, reductive evolution.

regulation the power of an embryo to continue normal or approximately normal development or re- generation in spite of experimental interference by ablation, implantation, transplantation, etc. regulative development embryonic development in which the fates of all parts of the embryo are not fixed before fertilization. In such development an ablated part can be repaired, or even separated blas- tomeres can form identical twins.

See mosaic devel- opment. regulator element See controlling elements. regulator gene a gene whose primary function is to control the rate of synthesis of the products of other distant genes. The regulator gene (rG) controls the synthesis of a protein repressor (R), which inhib- its the action of an operator gene (0G) and thus turns off the operon it controls. In the illustration below, the horizontal line represents a chromosome upon which four genes reside. The left gene can be distant from the other three closely linked genes (in fact, rG can be on a different chromosome).

Genes sG1 and sG2 are structural genes or cistrons of the conven- tional sort that produce specific proteins P1 and P2, respectively, through the formation of specific mes- senger RNA molecules. The repressor is present in exceedingly small amounts. It possesses two sites, one of which can attach to the operator and one of which can bind an effector (E) molecule. Once bound to E, however, the repressor changes shape and cannot attach to the operator. The effector mol-

Regulator gene

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