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Biomedical subjects

A L Koch

Publications and source records attributed to A L Koch.

At least 127 records · Page 7Linked to original sources
PubMed1974

The pertinence of the periodic selection phenomenon to prokaryote evolution.

A quarter of a century ago, it was pointed out that evolution can act in an important conservative way, in addition to its normal progressive mode. Evolution to a fitter form via changes at one locus means that the descendants of an individual with an improved locus or set of loci will supplant the previous population and carry with them the bulk of the total genotype of that original individual in asexual populations. Inasmuch as that individual is most likely to be wild type at most other loci, neutral and even other positively selected mutations will be reduced or eliminated from the population, if they are rare at the time of the evolutionary advance. In the present paper this problem has been set up for a computer simulation. The computations show the limits within which this effect functions and the conditions under which it does not. The conclusion is that it is likely that evolution at a locus proceeds in the course of many population replacements or revolutions, mostly via the rare occasions when the revolution carries a previously infrequent mutational type into abundance.

Biological Evolution↗
PubMed1974

Unimportance of counterflux in the energetics of "downhill" transport.

Adam Kepes suggested that the cellular transport and hydrolysis of orthonitrophenyl-beta-d-galactopyranoside is powered by the counterflux of the d-galactose resulting from beta-galactosidase action within the cell. His explanation would rationalize the unique insensitivity of this galactoside transport to energy poisons such as azide. But contrary to the predictions of this hypothesis, (i) there is no initial large inhibition that progressively lessens as galactose is produced. This was shown with a double wavelength stopped-flow spectrophotometer developed to eliminate interference from turbidity transients. (ii) The azide sensitivity does not increase with an external concentration of galactose sufficient to reverse the thermodynamic gradient. (iii) Mutation in galactose utilization or growth on highly catabolite-repressing regimens did not increase the azide sensitivity, and induction of galactose transport and metabolism did not decrease azide sensitivity. It was found that Kepes measurements must have contained two artifacts. One is that the control rate of hydrolysis decreases with time as the dense cell suspension becomes anaerobic. The other is that azide causes turbidity changes for some time after its introduction. If the former is avoided by magnetic stirring and the latter by double wavelength spectrophotometry or controls without substrate, the inhibition is constant from the earliest time that can be measured. It is therefore concluded that energy-unstarved cells, exposed to azide, still have adequate energy reserves to couple to the downhill transport, although their potential is not adequate to drive accumulation against a concentration gradient.

Azides↗
PubMed1972

Enzyme evolution. I. The importance of untranslatable intermediates.

The proportion of two allelic mutant forms of a haploid species can be calculated from six quantities, the original proportion, the two effective growth rate constants, the two mutation rate constants for the transition from one to the other, and the elapsed time. With a program for carrying out this calculation in a mini-computer, we set about investigating the rates of exploration of multiple intragene changes in populations of enormous numbers over a large number of cell generations. It seemed evident from the outset that unless in the past very different proportions of the different types of mutational changes occurred, then neither the numbers nor the times could have been of sufficient magnitude to account for enzyme evolution by multiple simultaneous changes within a gene to yield a superior protein. Rather, we propose that the more rapid path of enzyme evolution consisted of the sequence: 1) gene duplication, 2) inactivation of a gene copy by a chain-terminating mutation or other mutational change which suppresses transcription and/or translation, 3) multiple base-pair changes and/or small deletions and additions within the non-functioning gene, and finally, 4) reversion of the mutation which was suppressing translation. It is shown that this path will lead to faster advance, if the selective advantages of different forms are dependent on the function of the gene products at certain times in history, while at other times, although this function may be necessary, it is not limiting for growth.

Alleles↗
PubMed1972

Interaction of maltose transport with the transport of glucose and galactosides.

In cells of Escherichia coli possessing both maltose and galactoside permease, fluxes via one permease are independent of the substrate for the other permease. However, both fluxes are partially inhibited by glucose or alpha-methyl glucoside at low concentrations in cells grown on glucose. Neither maltose nor galactosides have an inhibitory effect on glucose permease function. These observations are consistent with the hypothesis that the number of glucose permease systems on the cell surface of such cells is much larger than the number for maltose or galactosides.

Biological Transport↗
PubMed1971

Temperature-sensitive mutants of Escherichia coli affecting beta-galactoside transport.

Six different temperature-sensitive (ts) mutants have been isolated which have parental beta-galactoside permease levels at low temperatures but have decreased permease levels when grown at high temperatures. These mutants were derived from Escherichia coli ML308 (lacI(-)Y(+)Z(+)A(+)). After N-methyl-N'-nitro-N'-nitro-soguanidine mutagenesis, ampicillin was used to select for cells unable to grow on low lactose concentrations at 42 C. Temperature-sensitive mutants were assayed for galactoside permease activity after growth in casein hydrolysate medium at 25 or 42 C by measuring both radioactive methylthio-beta-d-galactoside uptake and in vivo o-nitrophenyl-beta-d-galactoside hydrolysis. The six conditional isolates have decreased levels of galactoside permease which are correlated with decreased growth rates at elevated temperatures. The low permease levels are not due to a temperature labile lacY gene product but rather to a temperature labile synthesis rate of functional permease. Some of the mutants exhibit a ts increase in permeability as shown by the increased leakage of intracellular beta-galactosidase and by the increased rate of in vivo o-nitrophenyl-beta-d-galactoside hydrolysis via the nonpermease mediated entry mechanism. Preliminary evidence indicates that transport in general is decreased in these mutants, yet there is some specificity in the mutational lesion since glucoside transport is unaffected. All these observations suggest that these mutants have ts alterations in membrane synthesis which results in pleiotropic effects on various membrane functions.

Ampicillin↗