Spontaneous Somatic Mutations Research Articles

Spontaneous somatic mutation frequencies in the stamen hairs of 14 different Tradescantia clones heterozygous for flower color

A great variation in the spontaneous mutation frequency of stamen hair color (from dominant blue or purple to recessive pink) was found among 14 different Tradescantia clones heterozygous for flower color. When the mutation frequency was expressed either as pink mutant events per 10 3 hairs or per 10 4 hair-cell divisions, the maximum difference in the mutation frequency was found to be nearly 60 times; BNL clone 02 being the most stable and clone KU 20 the most mutable. Mutable clones exhibited especially higher mutation frequencies when they were placed outdoors (18.4°C average temperature) compared with when grown in a growth chamber (22.9°C average temperature) suggesting that they are temperature-sensitive clones. The 14 clones investigated could be classified into six different classes, each exhibiting different spontaneous mutation frequency levels.

The somatic generation of immune recognition

Antibody specificity is determined by structural v-genes that code for the amino acid sequences of the variable regions of antibody polypeptide chains. The present hypothesis proposes that the germ-cells of an animal carry a set of v-genes determining the combining sites of antibodies directed against a complete set of a certain class of histocompatibility antigens of the species to which this animal belongs. The evolutionary development of this set of v-genes in phylogeny is traced back to the requirements for cell to cell recognition in all metazoa. The hypothesis leads to a distinction between two populations of antigen-sensitive cells. One population consists of cells forming antibodies against foreign antigens; these lymphocytes have arisen as mutants in clones descending from lymphocytic stem cells which expressed v-genes belonging to the subset (subset S) coding for antibody against histocompatibility antigens that the individual happens to possess. The other population consists of allograft rejecting lymphocytes that express v-genes of the remaining subset (subset A) coding for antibody against histocompatibility antigens of the species that the individual does not possess. The primary lymphoid organs are viewed as mutant-breeding organs. In these organs (e. g. in the thymus), the proliferation of lymphocytes expressing the v-genes of subset S and the subsequent suppression of the cells of these “forbidden” clones, leads to the selection of mutant cells expressing v-genes that have been modified by spontaneous random somatic mutation. This process generates self-tolerance as well as a diverse population of antigen-sensitive cells that reflects antibody diversity. The proliferation in the primary lymphoid organs of lymphocytes expressing v-genes of subset A generates the antigen-sensitive cell population that is responsible for allo-aggression. The theory explains how a functional immune system can develop through a selection pressure exerted by self-antigens, starting during a period in early ontogeny that precedes clonal selection by foreign antigens. The hypothesis provides explanations for the variability of the N-terminal regions of antibody polypeptide chains, for the dominant genetic control of specific immune responsiveness by histocompatibility alleles, for the relative preponderance of antigen-sensitive cells directed against allogeneic histocompatibility antigens, for antibody-idiotypes, for allelic exclusion, for the precommitment of any given antigen-sensitive lymphocyte to form antibodies of only one molecular species and for the cellular dynamics in the primary lymphoid tissues.

Spontaneous somatic mutations. Structural studies on mutant immunoglobulins.

The precise alterations in the protein amino acid sequences of the immunoglobulin heavy chains of spontaneously arisen MOPC 21 mutant clones IF2 and IF1 have been determined. All the cyanogen bromide fra-ments of both heavy chains have been isolated and compared to the wild type CNBr fragments. For IF2, there is an internal deletion, from the wild type sequence, of 96 amino acids, from residues 121 to 215 inclusive. Moreover, in IF2, there are no disulfide bonds formed between heavy and light chains, presumably because of the deletion of the CH1 pseudosubunit. There are no other alterations in its covalent structure. For IF1, there is a deletion of the COOH-terminal 83 amino acids (residues 358 to 440, inclusive). Although IF1 heavy chain behaves on dodecyl sulfate-polyacryl-amide gels as if it were only 10 to 15 residues shorter than wild type, no other amino acid sequence differences from wild type are found. IF1 arose most likely by a nonsense mutation of a serine codon. For IF2, whose deletion is like that seen in some human heavy chain disease proteins, the most likely explanation is an error of recombination. The structure of IF2 suggests that the heavy chain variable region ends at a position homologous to residue 120 of the MOPC 21 heavy chain.

Spontaneous somatic frameshift mutation in a mouse myeloma

The precise alteration in the protein amino acid sequence of the heavy chain of IF3, a spontaneously-arising mutant of the P3K line of the mouse myeloma MOPC 21, has been determined. The secreted immunoglobulin of IF3 was more basic than wild type, and its heavy chain was smaller. The primary structure of IF3 heavy chain was studied by isolating all its CNBr fragments and selected tryptic peptides. The sequence of the mutant heavy chain was identical to wild type in the first 340 residues. The sequence of the remaining 14 residues of the mutant heavy chain was unique for immunoglobulins. The mutant sequence is related to the wild type by a two-base deletion in the coding sequence of the gene for MOPC 21 heavy chain. This explanation, a −2 frameshift, allows a unique sequence of 47 bases, that includes the bases deleted in IF3, to be deduced for MOPC 21 heavy-chain mRNA, and predicts the premature “ochre” termination for IF3.

Variation of spontaneous mutation frequency in Tradescantia stamen hairs under natural and controlled environmental conditions

Considering the lack of information about the variation in spontaneous mutation frequency, especially due to different genotypes and under different environmental conditions, a long-term scoring of spontaneous pink somatic mutations was carried out in the stamen hairs of three different clones of Tradescantia heterozygous for flower and stamen-hair color, keeping them under controlled or natural conditions. One of the clones, KU 20, was found to be highly mutable and also unstable showing about a 23-fold difference in the spontaneous mutation frequency depending upon the environmental condition. The other two clones, KU 7 and KU 9, were rather stable and much less mutable than KU 20. High negative correlations were found between spontaneous mutation frequency and temperature in clone KU 20, i.e., the lower the temperature (in the range of about 18 to 28°C) the higher was spontaneous mutation frequency, and this clone was found to be especially sensitive to temperature variation. A significant (at the 5% level) negative correlation between spontaneous mutation frequency and temperature was also found in KU 7, and a similar, but not significant tendency was observed in KU 9. The spontaneous somatic mutation frequency in older inflorescences of clone KU 20 was significantly lower than that in the younger inflorescences.

Variability in spontaneous somatic-mutation frequencies of a flower color locus in Tradescantia

Variability in spontaneous somatic-mutation frequencies of a flower color locus in Tradescantia

Spontaneous somatic mutation frequencies for flower color in several Tradescantia species and hybrids

Normal wild-type flowers of Tradescantia species and of certain interspecific hybrids vary in color from blue to violet to purple, but in many species occasional pink-flowered plants occur. Spontaneous pink mutant cells can be observed in petals and stamen hairs of plants heterozygous for flower color and mutation frequencies can be calculated per 10 3 hairs on per 10 5 stamen hair cells. These two frequencies are highly correlated but not completely proportional because of clonal differences in number of cells per hair. The lowest spontaneous frequencies were found in hybrid or putative hybrid clones and the highest (except for one mutable clone) found in heterozygous clones of pure species. The spontaneous frequency per hair varied from 0·48±0·15 to 5·21±0·20 × 10 −3 for hybrid (4430) or putative hybrid (02) clones, and from 2·15±0·16 to 16·98±1·25 × 10 −3 per hair for clones of T. bracteata, T. gigantea, T. ohiensis, T. paludosa and T. subacaulis. The pink mutation frequencies per 10 5 cells were calculated for three clones of T. subaccalis and varied from 11·8 to 58·9. Frequencies per 10 5 stamen hair cells varied from 3·65 for one scoring of the putative hybrid clone 02 to 23·0 for young plants of clone 4430 (a hybrid of T. hirsutiflora × subacaulis). Spontaneous frequencies for one set of scorings on petals of clone 02 gave an average of 27·5 × 10 −5 per cell—higher than the corresponding stamen hair frequencies, but scorings were at different times. For the mutable clone 0106, derived from clone 02, spontaneous pink mutation frequencies per 10 3 hairs varied from about 8·8±2·15 to 46·0±9·8 and per 10 5 cells from 35·7 to 227·8, depending upon length of time after cuttings were made. The variation in frequencies among clones is assumed to have a genetic basis but within a clone is thought to be influenced by such factors as age of plant or inflorescence, environmental conditions under which the plants are grown, the year or time of year scoring was done, and possibly by variation in scoring efficiency among different observers. The variation observed with date of scoring suggests the possibility of unidentified environmental mutagen(s) as the casual agent(s), but this has not been confirmed. The mutation frequencies observed in Tradescantia are compared with frequencies or rates in gametic and somatic cells of various plant and animal species.

Schizophrenia: initiation and development.

According to a recent theory, schizophrenia is confined to people with a particular genetic predisposition and the disorder arises from a specific breakdown in the central part of the system that controls growth (Burch 1964, 1968). We call diseases of this general class autoaggressive. Their pathogenesis has two distinctive phases: initiation and development. Initiation, which is a purely random process, entails a form of spontaneous somatic gene mutation in growth-control stem cells.