Average Mutation Rate Research Articles

Probability Distribution of Drug-Resistant Mutants in Unselected Populations of Mycobacterium tuberculosis

The fluctuation test shows that Mycobacterium tuberculosis mutates to resistance to isoniazid, streptomycin, ethambutol and rifampin spontaneously and at random. The average mutation rates for the drugs, in the same order, were calculated to be 2.56 x 10(-8), 2.95 x 10(-8), 10(-7), and 2.25 x 10(-10) mutation per bacterium per generation. The relatively high mutation rate to ethambutol resistance and the low mutation rate to rifampin resistance were confirmed by analyzing the increase in the proportion of mutants with time in a growing population of the tubercle bacilli. The highest proportions of mutants to be expected in unselected populations of the tubercle bacilli were calculated from the results of fluctuation tests.

DETERMINATION OF RADIATION-INDUCED MUTATION RATES OF RECESSIVE LETHAL ALLELES IN SACCHAROMYCES.

COMPARING X-ray inactivation curves of haploid and diploid strains of Saccharomyces, Latarjet and Ephrussi1 were the first to suggest that radiation inactivation of yeast cells may be caused by an induction of recessive and dominant lethal mutations. The first evidence of X-ray-induced recessive and dominant lethal mutations was obtained by Mortimer2 by means of tetrad analysis and specific mating experiments respectively. Recently the number of loci which may be induced by ultra-violet or X-rays to mutate to corresponding recessive lethal alleles as well as the average mutation rate of these loci has repeatedly been estimated after taking into consideration inactivation by dominant lethal mutations and other lethal effects3,4. Although the mean mutation rates determined in different laboratories do show a good correspondence, they are much higher than ultra-violet or X-ray-induced mutation rates from auxotrophic to prototrophic conditions or vice versa4,5. This striking difference in mutation rates demands a new independent investigation of the frequencies of radiation-induced recessive lethal mutations. If the estimated high mean mutation rates of recessive lethal mutations do correspond with reality, an investigation of specific mutation rates of a number of individual loci should reveal certain loci exhibiting high mutation rates.

A note on deaf mutism.

SummaryThe congenital deaf mute (HD) population of Northern Ireland, reported by Stevenson & Cheeseman, appears by maximum likelihood segregation analysis and the theory of detrimental equivalents to consist of three types.1. Autosomal recessives, complete penetrance, 68% of all HD cases, at least several loci, average mutation rate 1 × 10‐5 per locus, carrier frequency 0–080 per gamete.2. Autosomal dominants, high but not complete penetrance, 22 % of all HD cases, at least two loci, total mutation rate 5 × 10_5 per gamete.(a) Genes inherited from affected parents, 7 % of all cases.(b) New mutants inherited from normal parents, 15 % of all cases.3. Sporadic cases, due to unrecognized infection or more complex genetic mechanisms, 9 % of all cases.On the evidence, the hypothesis that the (non‐significant) excess of affected boys is due to sex‐linkage can neither be proven nor excluded. Ex hypothesi, sex‐linked cases account for less than 2 % of all HD cases, with a mutation rate of 2 × 10‐6 per X chromosome per generation.The hypotheses of heterozygote advantage, absence of dominant cases, synergistic effect of nonallelic recessive genes, and hypotruncate selection are shown to be inconsistent with the data. Studies on deaf mutism in other populations do not disagree with these conclusions.The theory of detrimental equivalents is extended to rare traits with retrospective ascertainment of consanguinity, giving estimates of carrier frequencies, number of loci, and mutation rates for recessive genes.

Genetic response ofAntirrhinum majus to acute and chronic plant irradiation

Clonal lines ofAntirrhinum majus heterozygous for flower color have been used to study somatic mutations induced by irradiating plants with chronic gamma rays from cobalt-60 and acute X rays. Pink or white flecks and sectors of various sizes on the purple flowers are interpreted as resulting from mutational events at different times in flower development. Acute X-ray treatment of pre-flowering stages caused no visible change in flowers opening prior to the 15th day thereafter. On the 16th to 19th days there was dense mottling, and by the 20th or 21st day numerous eight-cell mutant spots could be counted. The number of spots induced by 1,000 r of X rays was used to obtain a preliminary estimate of an average mutation rate for the three genes studied of 6.33×10−6 per cell per roentgen. Chronic irradiation in a gamma radiation field and greenhouse showed a linear response of mutation rate to daily dose rate, the actual rate being subject to seasonal variation. There were occasional indications of non-linearity but further tests have failed to show any significantly higher mutagenic efficiency of dose rates below 6 r/day. In plants removed from chronic gamma irradiation the frequency of mutation spots returns to the spontaneous level after about six weeks. The appearance, however, of mutant sectors on plants several months after exposure to both acute and chronic radiation indicates the induction of persistent genetic changes. Progeny tests of seeds and cuttings are planned to test the nature of these genetic events.

CHROMOSOME TRANSLOCATIONS INDUCED IN TRITICUM X AGROPYRON HYBRIDS BY X RAYS, PHOSPHORUS32, AND SULFUR33

THE PRESENT STUDY was intended both to measure cytogenetic effects of various radiation treatments on certain members of the Gramineae and to produce agronomically useful derivatives, if possible. The cytological facets are recorded here, while the practical aspects-the attempted translocation of desirable Agropyron genes onto synapsing Triticum chromosomes-are being transcribed for publication elsewhere. A few relative papers may be mentioned. Ehrenberg et al. (1949) placed kernels of barley and 4x and 6x wheat in 5' ml. of P32 solution, at 0.02 to 25.0 yc/grain, for 3 davs. A dose of 5 ,uc was generally lethal and yielded cytogenetic disturbances comparable to those from 25,000 r of X rays. Arnason et al. (1948) placed dormant kernels of 6x wheat, one per test-tube, in 0.1 ml. of Knop's solution with either 0.18 1tc or 0.018 ,uc of p32, for 13 days. Both concentrations were effective in causing chromosome breakage and rearrangements. This same group (Spinks et al., 1948) treated 6x wheat with p32 by sprouting the grains in water 48 hr. and then putting them (one per container) in test-tubes with either 0.18 or 1.8 Mc in 0.1 ml. of solution for 2 to 4 days. The higher dose was lethal; with 80 per cent uptake (measured), each seedling received ca. 1.4 tc. Similar tests with other genera showed that 1.8 yc Of p32 or Sr90 consistently killed or severely inhibited seedlings. Barley caryopses were soaked by Thompson et al. (1950) for 96 hr. in Petri dishes containing 0.625 to 10.0 Mc Of p32 and 0.1 ml. of water per grain. One pc of absorbed p32 was found to give the same average mutation rate as 19,500 r of X rays, and it was concluded: Radiophosphorus is highly mutagenic [and] is expected to become very useful in mutation work and plant breeding . Shebeski and Lawrence (1954) administered P32 to caryopses, seedlings, and pre-meiotic plants of