Twofold rotational symmetry
lymphocytes (q.v.) and cytotoxic T lymphocytes (q.v.). The tumor necrosis factor receptor (TNFR) is a transmembrane protein. Its extracellular domain binds to the TNF, while its intracellular portion combines with various adaptor proteins to form a complex that activates upstream procaspases. Thus it is the binding of a death ligand like the TNF to its receptor that signals the cell to activate its caspases (q.v.) and to undergo apoptosis (q.v.). tumor-specific transplantation antigen an anti- gen found on a tumor cell but not on the normal cells or tissues of the individual in which it arose, and that can lead to immune rejection of the tumor in situ or if transplanted. tumor suppressor gene synonymous with anti- oncogene (q.v.). tumor virus See oncogenic virus. tunicate See Ciona intestinalis. tunicin a cellulose-like fiber that makes up the ma- trix of the tunic that surrounds sea squirts.
The ge- nome of Ciona intestinalis (q.v.) includes a group of genes engaged in cellulose synthesis, and these evo- lutionary innovations may have arisen by horizontal transmission (q.v.) of genes from bacterial symbi- onts. Turbatrix aceti a free-living nematode whose de- velopmental genetics is under study, primarily for comparison with Caenorhabditis elegans (q.v.). Its cell lineage is known in part. turbid plaque See plaque.
Turner syndrome a group of abnormalities in hu- mans due to monosomy for the X chromosome. Such individuals are female in phenotype, but are sterile. The ovaries are rudimentary or missing. The syndrome is named after Henry H. Turner, the phy- sician who described the clinical features of the con- dition in 1938, but the underlying chromosomal ab- normality went unnoticed for 21 years.
Girls with Turner syndrome have normal intelligence but often have behavioral problems. These seem to be related to the parental origin of the X chromosome. Girls who inherit the X from their fathers are significantly better adjusted socially than those who inherit the X from their mothers. This finding suggests that there are imprinted genes on the X that somehow enhance social adjustment and only the paternal al- leles are switched on.
See Appendix C, 1959, Ford et al.; 1997, Skuse et al.; parental imprinting. http:// www.turner-syndrome-us.org turnover the dynamic replacement of atoms in a tissue or organism without any net change in the to- tal number of atoms. See Appendix C, 1942, Schoen- heimer. turnover number the number of molecules of a substrate transformed per minute by a single enzyme molecule under optimal conditions. twins pairs of individuals produced at one birth.
Monozygotic (MZ) or identical twins have identical sets of nuclear genes. MZ twins result from the sepa- ration of blastomeres and thus represent a form of asexual or clonal reproduction. Dizygotic (DZ) or fraternal twins arise when two eggs are released and fertilized. DZ twins, therefore, are no more similar genetically than are siblings that share only half of their genes, on the average. In humans, the fre- quency of monozygotic twinning is relatively con- stant (1/240 births). The frequency of dizygotic twinning varies in different races. In Caucasian pop- ulations, it is about double the frequency of MZ twinning.
See Appendix C, 1869, Galton; 1874, Dareste; 1875, Galton; 1927, Bauer. twin spots paired patches of tissue genetically dif- ferent from each other and from the background tis- sue, produced by mitotic crossing over in an individ- ual of heterozygous genotype during development of the organism. In the Drosophila example diagrammed on page 462, twin spots occur on a female of geno- type y +/+ sn. Most of the thorax and abdomen show wild-type pigment and long, black bristles, but there are adjacent patches of yellow and singed tissue.
These twin spots are clones of cells derived from the reciprocal products of an exchange between the singed gene and the centromere. twin studies the use of data collected from twins (q.v.) to evaluate the relative roles of heredity and environment in determining various human physical and behavioral characteristics. One method com- pares monozygotic and dizygotic twins reared to- gether and another compares identical twins who were adopted by different families and reared apart.
See Appendix C, 1875, Galton; concordance. twisting number the number of base pairs in du- plex DNA divided by the number of base pairs per turn of the helix. See pitch. twofold rotational symmetry the situation in which the two DNA strands of a duplex have the same base sequence when read with the same polar- ity. For example, the EcoRI (q.v.) endonuclease rec- ognizes a DNA segment six base pairs long that has twofold rotational symmetry. See palindrome.
two genes-one polypeptide chain participation of more than one gene in the coding of a given poly- peptide chain, as occurs in the production of immu- noglobulins. See immunoglobulin genes, one gene- one polypeptide hypothesis. two-point cross a genetic recombination experi- ment involving two linked genes. two-strand double exchange See inversion. Ty elements retroposons (q.v.) of the yeast Sac- charomyces cerevisiae.
The symbol Ty comes from transposon-yeast. There are 52 Ty elements per hap- loid yeast genome, and each consists of a central re- gion of about 5.6 kilobase pairs of DNA flanked by direct repeats about 330 base pairs long.
See Appen- dix C, 1979, Cameron et al.; 1985, Boeke et al. type specimen the individual chosen by the tax- onomist to serve as the basis for naming and describ- ing a new species. typological thinking the consideration of the members of a population as replicas of or deviations from a hypothetical type. tyr tyrosine. See amino acid. tyrosinase an enzyme that catalyzes the hydroxyl- ation of tyrosine to DOPA (q.v.). This spontane- ously oxidizes to DOPA quinone, and these mole- cules then polymerize to form melanin.
Human tyrosinase is made up of 529 amino acids, and it con- tains a signal peptide, two copper binding sites, and a hydrophobic transmembrane region. Any mutation that inhibits the ability of the protein to bind copper deactivates the enzyme. See albinism. tyrosine See amino acid. tyrosine-protein kinase See protein kinase. tyrosinemia a hereditary disease in humans arising from a deficiency of the enzyme p-hydroxyphenyl- pyruvic oxidase.
U 1. uracil or uridine. 2. uranium. U20 See nucleolin. ubiquinone coenzyme Q (q.v.). ubiquitin a highly conserved, 76 amino acid pro- tein ubiquitous in all eukaryotes, which regulates the selective, intracellular degradation of many proteins by the proteasome (q.v.), or in some cases, by the lysosome (q.v.) or vacuole (q.v.). Ubiquitin is a glob- ular protein with a functionally important “tail” at the C-terminus (q.v.).
The C-terminus glycine forms a covalent bond with a lysine residue or a lysine side chain on the substrate protein.
A polyubiquitin chain usually forms after a ubiquitin molecule con- jugates with the target protein, in which the C-ter- minus of each ubiquitin is linked to a lysine residue of the previous molecule. Ubiquitin-tagged proteins are then recognized and degraded by the proteasome or the lysosome/vacuole. Ubiquitination of proteins also serves as a signal for endocytosis (q.v.) and intra- cellular transport of proteins. In addition, ubiquitin plays a role in chromatin structure, since about 10% of the H2A histone molecules in nucleosomes are ubiquitinated.
Ubiquitin is encoded by a family of genes whose translation products are fusion proteins consisting of either a single ubiquitin molecule fused to a ribosomal protein, or multiple ubiquitins fused head to tail. In the former case ubiquitin-conjugated ribosomal proteins are targeted to the ribosome (q.v.), and ubiquitin is released following their incor- poration into the ribosomal-protein complex. In the latter case ubiquitin monomers are formed post- translationally through the action of deubiquitinat- ing enzymes (q.v.) that cleave the fusion protein.
See histone, nucleosome, otu, polycistronic mRNA, ubi- quitin-proteasome pathway (UPP). ubiquitin ligase See cyclins. ubiquitin-proteasome pathway (UPP) a highly specific and regulated intracellular process that func- tions to recognize, tag, and break down many pro- teins in eukaryotic cells. In this process a protein is tagged for degradation through covalent ligation to ubiquitin (q.v.), followed by degradation by the 26S proteasome (q.v.).
The conjugation of ubiquitin to the substrate protein (ubiquitination) occurs in mul- tiple steps. First, the C-terminus (q.v.) glycine resi- due of ubiquitin is activated by the enzyme E1 in an ATP-requiring step. Activated ubiquitin is then transferred to one of several E2 enzymes (ubiquitin- carrier proteins or ubiquitin-conjugating enzymes). Ubiquitin is further transferred from E2 to an E3 en- zyme belonging to the ubiquitin-protein ligase fam- ily.
Finally, the E3 enzyme catalyzes the covalent linkage of ubiquitin to the substrate protein. The specificity of ubiquitin-protein conjugation is depen- dent on the recognition of particular signals on the substrate protein by the appropriate E3 enzyme. The attachment of a ubiquitin molecule to the target protein is usually followed by the formation of a po- lyubiquitin chain, which is then recognized by the 19S regulatory particle of the proteasome.
The pro- tein is unfolded and translocated to the central cav- ity of the proteasome, the 20S core complex, where it undergoes ATP-dependent degradation.
The re- sulting peptides, 8-9 amino acids long, leave the pro- teasome and enter the cytosol where peptidases break them down further. Ubiquitin monomers are also released for future use by the activity of de- ubiquitinating enzymes (q.v.). Ubiquitin-mediated protein degradation is important for eliminating de- fective proteins. Furthermore, through the highly se- lective and regulated targeting of a wide range of substrate proteins, UPP controls numerous cellular functions, including cell-cycle progression, cellular signal transduction (q.v.), and regulation of tran- scription (q.v.).
UPP has also been linked to apopto- sis (q.v.) and to the processing of many MHC class 1 antigens. Many pathological conditions are associ- ated with abnormalities in ubiquitin-mediated pro- cesses. See Appendix C, 1980, Hershko et al.; otu, ritinitis pigmentosum (RP), SUMO proteins. UDPG uridine diphosphate glucose (q.v.). UH2A See ubiquitin. ultracentrifuge a powerful centrifuge that can at- tain speeds as high as 60,000 rpm and generate sedi- menting forces 500,000 times that of gravity. The instrument is used to sediment macromolecules. See Appendix A, 1923 Svedberg; centrifugation separa- tion techniques, centrifuge, sedimentation constant.