Showing papers on "Mutation (genetic algorithm) published in 1970"

Achondroplasia—a genetic and statistical survey

Abstract: Achondroplasia is the commonest form of skeletal dysplasia leading to dwarfism. The clinical features of short stature, large head, long trunk and stubby limbs are familiar to all. The designation achondroplasia was proposed by Parrot in 1878, although he was not the first to distinguish this disorder from rickets. Estimates of the frequency of achondroplasia differ widely. March (1941) found that in Denmark there was approximately one case in every 10,000 livebirths. Of these he believed SO% died within the first year of life giving a frequency of 20 per million in the general population of Denmark. As pointed out by Slatis (1956), this estimate is probably high as there is some confusion regarding the diagnostic criteria used and there appear to have been some recessive disorders and individuals with spondylo-epiphyseal dysplasia included (Silverman & Brunner, 1967). The incidence in the U.S. has been estimated to be 15 per million (Potter & Coverstone, 1948) and in Northern Ireland 28 per million (Stevenson, 1967). The primary defect in achondroplmia is unknown but is thought to result in inhibition of interstitial chondroblastic activity in the growth plate (Rubin, 1964). Only endochondral bone is involved, membranous bone formation continuing in the normal manner. Thus in the skull, the endochondral bone of the base is severely affected while the membranous bone of the vault is relatively uninvolved. This leads to the characteristic appearance of high forehead with frontal bossing and ‘scooped out ’ face. The dwarfism is of the short-limbed variety and of rhizomelic type ; that is, the upper arms and legs are shortened comparatively more than the distal segments. The spine is lordotic and the sacral tilt leads to prominence of the buttocks. This tilt, accompanied by the flat-roofed acetabula and the bowed legs leads to a duck-like walk. Although the hands are short and stubby, they appear large in comparison to the more abbreviated limbs. There is a characteristic space between the third and fourth digits which, together with the wide proximal phalanges, leads to difficulty in opposing the fingers, giving the characteristic three-pronged hand, the main en trident of Marie (1900). A new mutation is thought to be the cause of over 80 yo of cases, less than 20 yo being familial. Those achondroplasics who survive the first year of life have comparatively good health, although about half are thought to have self-limiting hydrocephalus in infancy. This may be due both to the small foramen magnum and to true megencephaly which is found as a non-skeletal effect of the achondroplasia gene (Dennis, Rosenberg & Alvord, 1961). The narrowed spinal canal enclosing a relatively normal spinal cord predisposes to neurological disorders caused by compression of the cord and nerve roots by osteophytes, prolapsed intervertebral discs, or deformity of the vertebral bodies (Vogl, 1962).

Mutation rate in Duchenne type of muscular dystrophy.

Abstract: The mutation rate in the Duchenne type of muscular dystrophy has generally been estimated by the indirect method of Haldane (1935) using his formula for X-linked recessive traits U=1/3 (l-f)x where U is the mutation rate, f the effective fertility of affected males, and x the incidence of affected individuals in the male population. Since the effective fertility of males with this disorder is zero, the mutation rate amounts to 1/3 of the incidence among males. Estimates on this basis have varied from 4-3 x 10-5 (Walton, 1955) to 9 5 x 10-5 per gene per generation (Stephens and Tyler, 1951). Perhaps the most satisfactory population study was that of Stevenson (1958) whose figures give a mutation rate of 6-0 x 10-5. Morton and Chung (1959) used the technique of segregation analysis of sporadic cases to obtain a figure of 8 9 x 10-5, but they appear to have included some cases of the benign X-linked (Becker) type of muscular dystrophy in their calculations, which invalidate the result obtained. Carrier detection techniques provide a basis for more direct estimation. The serum creatine kinase level is now well established as the most useful index of the carrier state. Results of surveys from many centres show that over-all about 75% of known carriers can be detected (Walton and GardnerMedwin, 1969). Investigation of large series of mothers of isolated cases of muscular dystrophy shows that relatively few of them are detected as carriers (Thompson, Murphy, and McAlpine, 1967; Gardner-Medwin, 1969). Most of the remainder are presumably the non-carrier mothers of those cases which have arisen by new mutation. A considerable problem, however, is posed by the possibility that some cases of 'Duchenne' muscular

Genetic locations of uvrD and pol genes of E. coli.

Abstract: SummaryUvrD maps between metE and ilv genes, and pol maps near metE, between metE and rha genes.

The Evolution of Dominance

Abstract: R. A. Fisher in 1928 introduced his theory of the evolution of dominance. In bare outline the theory states simply that if an unfavourable gene is continuously being produced by mutation, other genes which modify the action of this gene will eventually be selected which will give individuals carrying the gene a phenotype resembling the favoured wild-type phenotype. Since the gene occurs initially to a large extent in the heterozygous rather than homozygous state, it is the heterozygote which is principally subject to this modification. The process is expected to be a very slow one, since the fraction of the population which is exposed to this selection is very small.

A multisite-mutation map of the leucine operon of Salmonella typhimurium.

Abstract: LEUCINE is synthesized in Salmonella typhimurium by the pathway shown in Figure 3 (BURNS, UMBARGER and GROSS 1963). The genes specifying the leucine-forming enzymes are clustered in one region of the genome between ara and azi and comprise an operon (MARGOLIN 1963; BURNS, CALVO, MARGOLIN and UMBARGER 1966; CALVO, MARGOLIN and UMBARGER 1969). We describe here the isolation and characterization of a large number of leucine auxotrophs and the construction of a detailed multisite-mutation map of the leucine operon.

A bacterial mutation which affects recognition of the N gene product of bacteriophage lambda.

Abstract: In bacteriophage ~, the expression of most viral functions is dependent on the positive regulatory action of gene N (Thomas, 1966; Skalka et al., 1967; Radding and Echols, 1968). However, the mechanism of action of the N protein remains unknown. This paper deals with a new bacterial mutat ion which might be relevant to this problem. This mutat ion (ton, for recognition of N) which is very closely linked to the locus for rifamyein resistance, prevents growth of phages harbouring an alteration in gene N, even though this alteration remains undected in ton + strains. This situation suggests a direct interaction between the product of the bacterial gene ron and the /V protein. Our original aim was the isolation of mutations which would interfere with the expression of nonsense suppressors. For this purpose, we selected survivors following infection of a nitrosoguanidine-mutagenized culture of E. coli strain E213 (a su3 derivative of H / r P 4 X ) with phage 2 c I~0~5 sus N~; since N mutants do not kill upon infection, one expects tha t bacterial mutants in which the amber suppressor is not expressed will survive infection with this phage. Among those survivors which are not simply 2-resistant, a majori ty have the suppressor gene su 3 itself partially or completely inactivated. In one strain, however, the suppressor is still present and yet 2 sus N~ does not plate. This strain is referred to as X 15 and the mutat ion it carries, as ton. The ron mutat ion is 18% eotransducible with mets and maps in the region between arg]t and purD. This region contains rifamycin resistance mutations known to alter RNA polymerase (Tocehinl-Valentinl et al., 1968). Linkage of the ron mutat ion to the ri/-r locus was studied by phage P 1 transduction. Donor phage grown on a prototrophic X15 derivative was used to transduce a arg]~ ri/-r p u t D strain. Ri]-r and ton phenotypes were scored among the arg + or put+ t ransductants; only 2,2% of the arg+ t ransductants are ri/-s ron + recombinants and 1,8% of the pur+ t ransductants are ri / .r ron reeombinants. These findings establish a very close linkage of the two mutations. We prepared a set of ton strains, isogenic except for the amber suppressors (sul, su2 , su3 or su6) . I t was found tha t 2 sus ~V 7 does not grow on these strains, whatever the suppressor present. Among 32 other 2 sus mutants tested, two

Cryptic mutants of bacteriophage T4.

Abstract: HE apparent mutation rate depends upon a number of contingencies: the Tprimary error rate, the probability o€ repair, error avoidance by the apparatus of DNA replication, and the probability of detection. The probability of detection of those base pair substitutions which produce an amino acid substitution appears to be highly variable, and presumably reflects the sensitivity of polypeptide functions to small variations in primary structure. Fine-scale mapping has often revealed a highly nonrandom distribution of mutations among sites. In the T4rZZ system, for instance, 809 of the first 1609 independently isolated mutants were observed to map into only two sites (BENZER 1961). Genetic data indicate that the number of rZZ sites capable of mutation by base pair substitution is about 1700 (EDGAR et al. 1962; STAHL, EDGAR and STEINBERG 1964), and this estimate is supported by quasi-chemical measurements (GOLDBERG 1966). When frameshift mutations are excluded from consideration, however, fewer than 3% of these potential sites have been identified (FREESE 1959; BENZER 1961; ORGEL and BRENNER 1961; see Chapter 5 of DRAKE 1970). What then is the nature of the apparently immutable sites? Two possible answers deserve serious consideration: many sites are extremely weakly mutable, or else many amino acid substitutions are undetected in standard screening systems because they fail to exert significantly deleterious effects upon protein function. The first possibility is supported by the observation that TbZZ amber and ochre mutations, which are likely to be detected with uniformly high efficiencies, nevertheless appear at very different frequencies at different sites during the course of hydroxylamine mutagenesis (BRENNER, STRETTON and KAPLAN 1965). The second possibility is supported by the observation that a disproportionately large fraction of T4rZZ base pair substitution mutants contain amber codons, compared to the fraction expected from random base pair substitutions (BENZER and CHAMPE 1961; CHAMPE and BENZER 1962). The second possibility is also supported by the observation that approximately one-quarter of the beginning of the rZZB cistron is dispensable (DRAKE 1963). Furthermore, the rZZ function is overproduced by the (possibly trivial) criteria of the standard screening system, since many rZZ ochre mutants are well suppressed even though the efficiency of chain propagation is well below 10% (BRENNER and BECKWITH 1965). We have approached the problem of the missing sites by designing procedures to increase the efficiency of detection of leaky mutants. It was already clear that temperature-sensitive ( t s ) mutations of the rZZ region are readily obtained

Genetical theory and the "inborn errors of metabolism".

Abstract: In recent years considerable advances have been made in our understanding of how the genetic constitution of an individual determines the enzymes and proteins that he makes; and how abnormal genes which have arisen from specific mutations in earlier generations may, because they result in the abnormal synthesis of a specific enzyme or protein, lead to the occurrence of a characteristic form of disease. The central idea is that the primary sequence of amino-acids in each of the distinctive polypeptide chains that may occur in an enzyme or protein is coded in the sequence of purine and pyramidine bases in the deoxyribonucleic acid (D.N.A.) of a corresponding gene. It can be conveniently expressed by the simple formula:

Natural selection and the origin of life.

Abstract: At least four conferences on the origin of life have been convened and the proceedings published in the last fifteen years [1-4], yet central and difficult questions remain unanswered [5]. Those who explain the event in terms of known phenomena believe either in unrealistic quantities of time and reagents, or in unspecified constraints that limited random reactions to a small and appropriate range. Solutions proposed for one set of problems often raise new problems of equal or greater magnitude. If the probability of life's origin is low according to present concepts, this foUows chiefly from the apparent need of the first form of life for a self-copying mechanism, which caUs in turn for a highly specialized macromolecule. These requirements could be bypassed if reproduction by the environment could take the place of reproduction by self. Reproduction by the environment can, in fact, be postulated in a form that satisfies the elementary requirements of natural selection. Such selection could, therefore, have guided evolution during the development of more complicated genetic mechanisms. My first purpose is to review and to integrate some earlier proposals for the origin oflife that can be interpreted as reproduction by the environment [6-9]. This is not enough, because when self-copying is avoided in this fashion, two capacities essential in organic evolution appear also to be bypassed: the capacity to mutate and the capacity to accumulate biological information. My second purpose is to explain how these two capacities may exist in the absence ofcopying. This thesis admittedly conflicts with what many geneticists regard as self-evident truth. It wiU also be necessary to indicate how evolution could proceed along a continuous path from such beginnings to more familiar forms. FinaUy, I shaU urge a new direction for research into the origin of life.

Hin- und Rücksegregation eines außerkaryotischen Gens bei Chalamydomonas reinhardii

Abstract: Streptomycin-sensitive revertants (=prim. ss) result from the streptomycin-dependent mutant sd3 with a frequency of 10-7 to 10-6 by mutation. The newly formed ss-revertants have besides ss-genes also sd-genes. Therefore, most of the revertants are able to segregate sd-cells (=sec. sd) on streptomycin-medium up to a frequency of 10-2. With increasing time of cultivation on streptomycin-free medium the number of the sd-genes decreases continuously until the power of segregation expires.

Developing Genetic Algorithm Library Using Java for CFG Induction

Abstract: Grammar Induction is the process of learning grammar from training data of the positive (S+) and negative (S-) strings of the language. The paper discusses the approach to develop a library for inducing the context free grammar using Genetic Algorithms. Genetic Algorithm used for the induction library produces successive generations of individuals‟ chromosome, computes their fitness value in every step of generation and finally select the best out of the total number of generation or when the termination condition (threshold) is meet. The library also deals with the issues in implementation of the algorithm, chromosome representation, evaluation, selection and replacement strategy and the genetic operators for crossover and mutation. The paper also addresses the solution of the problem like useless production, left recursion, left factor, and unit production etc. The library has been implemented and the results obtained for the set of various problems like balanced parenthesis, two symbol palindromes and equal number of 0s and 1s are presented.

Genetic location in Escherichia coli K-12 of the ultraviolet-sensitive mutation uvrD3.

Abstract: A host cell reactivation-negative mutation, uvrD3, in Escherichia coli K-12 is located between ilv and metE.