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Evidence for selection by male mating success in natural populations of Drosophila pseudoobscura.

Gene arrangement frequencies were determined at two stages in the life history of Drosophila pseudoobscura taken from nature. Three populations in the central highlands of Mexico were each sampled twice during 1976. Gene arrangement frequencies were measured in adult males and in larvae that were the offspring of females collected at the same time. The adult males were in all likelihood a representative sample of those who fathered the larvae produced by the wild females. Differences in gene arrangement frequency between these two life stages should indicate the operation of natural selection. One-third of our comparisons of common gene arrangement frequencies in males and in larvae from the next generation were statistically significant, as were one-third of our comparisons of total frequency arrays in the two life stages. We consider the components of selection that could produce such frequency changes and reason that male mating success must be the major one. Gene arrangement frequencies in the Mexican populations fluctuate within wide bounds. Selection must act to retain the polymorphism in the face of this flux in gene arrangement frequencies, and we suggest that male mating success plays an important role.

Animals

Genetic drift in a cline.

A model is developed of genetic drift in a cline maintained by spatially varying natural selection and local dispersal of individuals. The model is analyzed by an approximation scheme which is valid for weak selection and small migration rates. The results, which are based on numerical iterations of the approximate equations, are that the cline is less steep than predicted on the basis of the deterministic theory but that for weak selection the correlation between random fluctuations in neighboring colonies is approximately the same as in models of migration and drift in the absence of selection.

Biological Evolution

Finlay-Wilkinson random regression for yield and yield stability prediction in cereals.

Year-to-year climate variability poses a challenge for agriculture by increasing crop yield variability; therefore, there is a need to identify genotypes that can withstand these fluctuations. With the right selection criteria, genotypes with yield stability across variable environmental conditions can be selected. Methods such as Finlay-Wilkinson random regression (FWRR) may allow us to use sparse datasets-common in plant breeding pipelines-and incorporate genomic data to leverage phenotypic information from related genotypes to predict yield stability. Our objective was to examine how the number of environments and the variance among those environments affect stability predictions. We also integrate FWRR as a genomic prediction tool for characterizing yield stability, comparing it to the traditional genomic prediction models as a reference. We used three datasets: one highly unbalanced dataset for oats (Avena sativa L.) and two completely balanced datasets with different numbers of environments for barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.). We fit standard Finlay-Wilkinson (FW) and FWRR models to estimate grain yield and stability under various scenarios. We found that the estimated stability values obtained were similar using balanced datasets for FW or FWRR. FWRR also achieved moderate predictive ability for stability using unbalanced datasets under 10-fold cross-validation (CV1) with new genotypes. In terms of environmental representation, selecting the right set of environments for inclusion in the model was more important than adding more environments. Our results suggest the possibility of using FWRR to select stable genotypes earlier in line development, as well as to design resource-efficient stability-testing schemes.

Hordeum

Interactions of Folch-Lees proteolipid apoprotein with planar lipid bilayers.

Water-soluble Folch-Lees proteolipid apoprotein from bovine CNS white matter induces a voltage-dependent conductance in black lipid membranes. Na+ is required for the induced conductance change but the established conductance has very low ionic selectivity. The induced conductance fluctuates with a minimum amplitude of 10(-11)--10(-10) mho. The magnitude of the conductivity change is dependent on protein concentration and on the composition of lipid bilayers. At a fixed voltage the induced conductance of a phosphatidylcholine-cholesterol membrane is proportional to the sixth power of the protein concentration and the first power of Na+ concentration. The interactions between the apoprotein and the lipids are both electrostatic and hydrophobic, but the interaction leading to the conductance increase appears to be mainly hydrophobic. Both the increase in conductance and the current fluctuations remain after extensive washing of the chambers to remove the protein. Furthermore, pronase or glutaraldehyde added to either the cis or trans side of the membrane does not affect the apoprotein-established conductance. However, if the bilayer is formed in the presence of both the apoprotein and pronase or if the apoprotein is treated with pronase prior to its addition to the chamber, no conductance change is observed. The association of the apoprotein with the membrane thus appears to render the protein inaccessible to proteolytic digestion, suggesting that the apoprotein is at least partially imbedded in the membrane interior.

Animals

Evolutionary processes and evolutionary noise at the molecular level. II. A selectionist model for random fixations in proteins.

On account, notably, of a competition between different component functions for individual sites in polypeptide chains, each protein molecule represents a functional compromise, with some functions optimized, but the overall state of the molecule "suboptimal". The proposal is made that the selection coefficient relating to a protein molecule under given conditions can in principle be broken down into partial selection coefficients relevant to the different functions that the molecule carries out. At general-function sites, each fixation improves some function, while others deteriorate, at first nonsignificantly, and the overall adaptive state of the molecule fluctuates around its maximum. A selective mechanism is described whereby kaleidoscopic changes in primary structure at variable sites are indefinitely promoted, independently of any environmental changes and with the molecule remaining close to a state of maximal overall adaptation. The paradoxical aspect of this proposal is analyzed. The implication of specific functions in substitutions at general-function sites is noted. Further, it is shown that a certain category of changes in the internal environment of the organism can be integrated into the constant-environmental model for selection. Genetic sufficiency is considered a notion more adequate than genetic optimality for describing biological fitness and for providing a basis for the present model. On this basis selection occurs without genetic load. Multipolymorphism is one of the consequences. Several lines of evidence, in particular observations on polymorphism in deep sea organisms, seem to support the model. It is pointed out that it provides a theoretical foundation for a molecular evolutionary clock. The theoretical constancy of the clock depends on the constancy of functional density. The question of the evolution of functional density is examined. Comparisons of observed substitution frequencies with values expected on a random basis are rejected as a measure of the contribution to evolution of nondetermination. They are considered to reflect a hierarchy in the resistance of the molecules to different amino acid residues as substituents. A limited component of "true" randomness, again accompanied by selection, is on the other hand provided by the model. Most amino acid substitutions are considered evolutionary noise, even though noise compatible with selection. It is proposed that evolutionary significant substitutions may be identified by monitoring changes in functional density and weighted functional density.

Alleles

Genetic characterization of hydroxyurea-resistance in Chinese hamster ovary cells.

Hydroxyurea is an excellent selective agent for obtaining drug-resistant mutants. At a frequency of approximately 1 X 10(-5) it was possible to select, in a single step, colonies that exhibited significant resistance to the cytotoxic effects of the drug. These hydroxyurea-resistant cell lines maintained their resistant phenotype after extensive cultivation in the absence of the drug. Reconstruction experiments indicated that the expression of hydroxyurea-resistance and the frequency of drug-resistant colonies was independent of cell densities up to 5 X 10(5) cells per 100-mm selection plate. Luria-Delbrück fluctuation analyses indicated that the appearance of hydroxyurea-resistant cells in wild type populations occurred spontaneously and at a rate of 4.8 X 10(-6) per cell per generation in the presence of 0.33 mM drug. Studies with the mutagen, ethyl methane sulfonate indicated that it was capable of increasing the frequency of hydroxyurea-resistant cells by a factor of approximately 10. Also, cell-cell hybridization experiments showed that hydroxyurea-resistance behaves as a dominant or codominant trait and that hydroxyurea-resistance was a useful new genetic marker for selection of somatic cell hybrids. Furthermore, similar to many other drug-resistant cell lines hydroxyurea-resistant cells were found to exhibit an altered sensitivity to a number of non-selective agents (guanazole, N-carbamoyloxyurea, formamidoxime, and hydroxyurethane). Except for guanazole these compounds are structurally very similar to hydroxyurea and may be expected to have similar modes of action. The results presented in this paper support the view that hydroxyurea-resistance is expressed as a normal genetic trait and is a useful genetic marker for somatic cell genetic studies.

Animals

Long-term mortality study of steelworkers. IX. Mortality patterns among sheet and tin mill workers.

As a result of findings of an earlier report in this series, this study examines the updated cause-specific mortality of men employed in the sheet and tin mill areas of the steel industry. In order to investigate possible relationships between occupational responsibilities or exposures and mortality from specific causes, the sheet and tin mills have been subdivided into 13 mutually exclusive work areas. Detailed analysis is limited primarily to white workers due to the small number of nonwhites in these areas. The most important observations are: 1. Increased overall mortality appears for men employed in 1953 in the sheet finishing and shipping area, confirming the findings of Lloyd, et al. The earlier observation of a significant excess in deaths from vascular lesions of the central nervous system does not hold over time. The previously noted excess for this cause may be related to selective factors or an extreme chance observation. The excess in mortality from all causes of death, which occurs over several disease categories, may not be a result of occupational exposures, but rather some selectivity. 2. Significant excesses in mortality from arteriosclerotic heart disease are noted among men employed in batch pickling and sheet dryer operations, which is in agreement with the earlier findings. Increased risks of dying from hypertensive heart disease are seen in the coating area. 3. Cancer of the lymphatic and hematopoietic tissues is found to be a significant source of excess mortality for workers in the heat treating and forging and tin finishing and shipping work areas. 4. Steelworkers employed in the annealing-normalizing work area show an excess in deaths from nonmalignant respiratory diseases, primarily pneumonia. Further study in these areas should attempt to investigate whether factors in the work environment may be responsible for the observed excess mortalities. More specifically, work should be done to find out whether men employed in heat treating and forging and tin finishing and shipping work in close proximity to chemicals or radiation exposure and whether workers employed in the annealing-normalizing area are exposed to any kind of oil, vapor, or chemical which might be irritating or infectious to the respiratory system. A similar analysis for men working in the batch pickling and sheet dryers and coating areas would also be worthwhile. The main emphasis of any future study should lie upon investigating whether the observed excess mortalities are due to any environmental factor, selection for health, or random fluctuation.

Alloys

Fluctuations in buoyant density during the cell cycle of Escherichia coli K12: significance for the preparation of synchronous cultures by age selection.

The buoyant densities of Escherichia coli K12 were investigated by isopycnic centrifugation in gradients of colloidal silica (Ludox) and polyvinylpyrrolidone. Bacteria from an exponential culture in a defined medium supplemented with hydrolysed casein banded at densities between 1-060 and 1-115 g ml-1; the mean density was 1-081 g ml-1. At the higher densities, two populations of cells were present: smaller cells were approximately twice as numerous as, and half the modal volume of, the population of larger cells. A homogeneous population of cells of intermediate volume equilibrated in the least dense region of the density band. Synchronous cultures were established by inoculating cells selected from the most or least dense regions of the band into spent growth medium. The results are consistent with a fluctuation between maximal density at cell birth and division, and minimal density near the middle of the cell cycle. In synchronous cultures prepared by continuous-flow age selection, the first division occurred after a period that was significantly shorter than the length of subsequent cell cycles. Cells selected by this procedure were of similar mean density to those in the exponential culture but were more homogeneous with respect to size. The possibility that the smallest (and densest) cells in an exponential culture are retained in the rotor, and are thus excluded from the synchronous culture, is discussed.

Cell Division

Cellular autolytic activity in synchronized populations of Streptococcus faecium.

The autolytic capacity of Streptococcus faecium (S. faecalis ATCC 9790) varied during synchronous cell division. This phenomenon was initially observed in rapidly dividing populations (TD=30 to 33 min) synchronized by a combination of induction and size selection techniques. To minimize the problems inherent in studies of cells containing overlapping chromosome cycles and possible artifacts generated by induction techniques, the autolytic capacities of slowly dividing populations (TD=60 to 110 min) synchronized by selection only were examined. Although the overall level of cellular autolytic capacity was observed to decline with decreasing growth rate, sharp, periodic fluctuations in cellular autolytic capacity were seen during synchronous growth at all growth rates examined. On the basis of similar patterns of cyclic fluctuations in autolytic capacity of cultures synchronized by (i) selection, (ii) amino acid starvation followed by size selection, and (iii) amino acid starvation followed by inhibition of DNA synthesis, a link of such fluctuations with the cell division cycle has been postulated.

Amino Acids

Interactions between intrinsic membrane protein and electric field. An approach to studying nerve excitability.

We have approached the problem of nerve excitability through three questions: (a) What is the diagram for a channel? That is, what conformational states can the protein assume, and what transitions between these conformations are permitted? (b) What is the channel conductance associated with each conformation the channel can assume? (c) How do the rates for conformational transition depend upon membrane potential? These three questions arise from a standard statistical mechanical treatment of a nerve membrane containing several classes of identical, independent channels. Gating of channels, in this view, is associated with conformational changes of the channel protein, and it is assumed these conformations are distinct. The precise formulation of these questions is presented in terms of the theoretical treatment, and the approaches we have taken to answer the questions are indicated. Our present results indicate: Transition rates should depend exponentially on membrane potential over a limited voltage range, but probably will show a more complex dependence for extremes of the range; channels probably can take on only two conductances, open and shut, but more complicated situations are not entirely excluded; the diagram for a channel cannot be determined from standard voltage clamp data alone, but by studying gating currents and conductance fluctuations, it should be possible to select between alternative plausible physical mechanisms.

Biological Transport

Haplotype stacking to improve stability of stripe rust resistance in wheat.

Genotype-by-environment interaction analysis and haplotype-level characterisation provide novel insights into the stability of stripe rust resistance. Breeding selection strategies are proposed to achieve rapid and stable genetic gains across environments. This study investigated stripe/yellow rust (YR) responses in the Vavilov wheat diversity panel evaluated across 11 field experiments conducted in Australia and Ethiopia during 2014-2021. Genotype-by-environment interaction (GEI) was analysed using a factor analytic (FA) model. Genotype-level selection was performed with overall performance (OP) and root-mean-square deviation (RMSD), which reflected average performance and stability of YR resistance across environments, respectively. Genomic estimated breeding values (GEBV) for these traits were calculated and compared with those from a multi-trait GBLUP model with average performance represented by the mean GEBV across environments and stability by the standard deviation of GEBV across environments. The FA-based and multi-trait GBLUP GEBV had high correlations. Haplotypes with large effects on OP and RMSD were identified using the local GEBV method. Favourable haplotypes were then used for stacking in breeding simulations, using the Vavilov collection as a base. Compared to truncation selection, optimal haplotype selection (OHS) using an artificial intelligence (AI)-based algorithm achieved longer-term genetic gains for both OP and RMSD (after many generations) by initially selecting founder parents that maximised favourable haplotypes. Simulations using YR responses from diverse environments that mimicked fluctuating environmental conditions across seasons were conducted to evaluate strategies for selection of YR resistance that is stable across years. Strategies which gave most weight to OP, but some weight to RMSD were optimal in these conditions, and substantially reduced variation of performance across years. This study provides useful information for breeding cultivars with both high YR resistance and high stability of resistance across environments.

Triticum

Metabolic niche differentiation and napA evolution stabilize partial denitrification in wastewater ecosystems.

Although partial denitrification (PD) is increasingly applied as a nitrite-supplying strategy for anammox-based nitrogen removal, the ecological distribution, metabolic specialization, and genomic determinants of stable nitrite accumulation remain poorly understood at the ecosystem scale. Here, we reconstructed 516 high-quality metagenome-assembled genomes (MAGs) using high-depth metagenomic sequencing of 107 wastewater treatment plants and classified denitrifiers according to their nitrite production or consumption capacities. Of these genomes, 23% (120 MAGs) were classified as partial denitrifiers, 41% (211 MAGs) as complete denitrifiers, and 36% (185 MAGs) as nitrite-reducing denitrifiers, revealing pronounced functional partitioning rather than dominance by complete denitrification pathways. Comparative genomics showed that partial denitrifiers possess metabolic architectures favoring rapid carbon oxidation and NADH generation while exhibiting constrained NADPH production and biosynthetic investment, thereby promoting nitrate-to-nitrite conversion but limiting subsequent nitrite reduction. Nitrite accumulation does not result from incomplete denitrification pathways but from metabolic niche differentiation. These metabolic trade-offs were further associated with the evolutionary divergence of the periplasmic nitrate reductase gene, napA, which displayed distinct sequence characteristics and genomic contexts between partial and complete denitrifiers. Integration of carbohydrate-active enzyme repertoires further revealed metabolic complementarity between partial denitrifiers and anammox bacteria, supporting efficient carbon handoff without direct substrate competition. From an engineering perspective, operating conditions that impose moderate electron limitation, such as low or fluctuating C/N ratios and intermittent carbon feeding, may selectively enrich partial denitrifiers and enhance a stable nitrite supply for PD-anammox systems. Together, these findings identify PD as a predictable ecological state shaped by genome-encoded metabolic specialization and provide a mechanistic basis for designing robust, low-carbon nitrogen-removal processes.

Anammox

Absence of selection of HIV-1 variants in vivo based on transcription/transactivation during progression to AIDS.

The activity of the human immunodeficiency virus type 1 (HIV-1) transactivation protagonists tat and TAR has been analyzed from sequential primary material. The sequences were amplified from uncultured peripheral blood mononuclear cells. Despite fluctuations within the tat and TAR quasispecies there was no obvious selection for a variant encoding more powerful transactivation components either in vivo or ex vivo, indicating that this system is not exploited during disease progression. The basal levels of the natural promoters were, depending on the cell line, two- to fourfold higher than that of the reference promoter, itself derived from ex vivo adapted HIV-1 Lai.

Acquired Immunodeficiency Syndrome

Multilocus behavior in random environments. I. Random Levene models.

In this paper the consequences of natural selection acting on several loci simultaneously in a spatially fluctuating environment are described. The fitnesses of the genotypes are assumed to be additive both within and between loci. The environment is assumed to be made up of a very large (effectively infinite) number of patches in which fitnesses are assigned at random. The resulting deterministic model is called a Random Levene Model and its properties are approximate by a system of differential equations. The main equilibrium properites are that (1) the linkage disequilibrium is zero and (2) the correlations in fitness between alleles at different loci are the principle determinants of the dynamic inter-locus interactions. Although there is no epistasis as conventionally defined, the equilibrium state at the two loci are highly interdependent, the governing principle being that two alleles at different loci whose fitness are negatively correlated across environments have a higher overall fitness due to the reduction in their variance in fitness through the negative correlation. When a large number of loci are considered, they naturally fall into correlation groupings which lead to an enhanced likelihood for polymorphism over that predicted by single-locus theory.

Biological Evolution

The variability of innate darkness preference in mice: an evaluation of Ungar's design.

This study attempted to elucidate the controversy surrounding the experiments of Ungar examining the effects of scotophobin on dark preference in mice. The behavior of 45 noninjected mice in the type of maze described by Ungar was examined. Seven subsequent tests were conducted for dark box time (DBT) and motor activity. In general, the results indicated that DBT in all subpopulations of mice selected according to different criteria on the preference test fluctuated during the course of experimentation. Further, on the basis of the present data, the problem of summation effects from combined probabilities in the series of independent comparisons was readily apparent, so that the probability of obtaining significant differences between groups was increased as the results of Ungar's data analysis. A strong relationship between motor activity and DBT was also obtained, suggesting that other, nonspecific factors may influence motor activity and shorten the elevation of DBT.

Animals

[The influence of bemegride on frog spinal cord root potentials].

The effect of the convulsant bemegride (beta-ethyl-beta-methyl-glutharimide) on the electronic potentials in the frog spinal roots was investigated in situ. Intravenous injection of the bemegride subconvulsant doses (6.8 +/- 2.7 mg/kg) depressed rapidly the electrotonic dorsal root potentials (DRP) evoked by a stimulation of the adjacent dorsal root (DR) or the ventral root (VR). They were reduced by 55--67% 3-6 min after the bemegride injection. The effect of bemegride was reversible and the DRP amplitude restored its initial value within an hour. Ventral root potentials after bemegride injection revealed only greater amplitude fluctuations. A conclusion is made that bemegride is a selective and potent depressor of the primary afferent depolarization in the frog spinal cord.

Animals

Acne vulgaris. Current concepts of pathogenesis and treatment.

Although the basic cause of acne vulgaris remains unknown, considerable data that concern its pathogenesis and that have been accumulated in recent years allow a rational and therapeutically successful approach to the management of this disorder. To date, there is no single treatment for acne. Therapy must be individualized, with appropriate variations and modifications as the degree or severity of this disorder fluctuates. Today, this goal can be achieved by proper selection of available medications, coupled with the cooperation of the patient, and the knowledge, continued interest, and enthusiasm of the physician and his staff.

Acne Vulgaris

The influence of corticotherapy on mitogen induced lymphocytotoxicity in bronchial asthma.

In a previous study the hyperreactive lymphocytes in bronchial asthma (BA) have been documented by mitogen induced cell-mediated cytotoxicity (MICC). Since MICC was considerably low in patients receiving substantial doses of steroids, further investigation was conducted. BA patients were divided into three groups: the first was given daily steroids, the second was given steroids on alternate days and the third consisted of a longitudinal follow-up study on the same individual being on different doses of steroids. Mixture of blood lymphocytes, phytohemagglutinin and Cr51 labeled target cells (P815/DBA2) were incubated in ratio 10:1 for 12 hours. Subsequently the cytotoxic potential of effector lymphocytes was detected by measuring the Cr51 in the supernatant of reacting cells. It was observed that cytotoxic correction index (CCI = Patient/Control Cytotoxic Index) was significantly lower among those in the first group and when the dose of Prednisone or its equivalent exceeded 40 mg/day. Comparison of the CCI between patients from the first and second groups supports alternate day corticotherapy in BA. Considerable fluctuation of CCI was apparent in the third group. Selected high doses of steroids suppressed MICC. This effect is reversible and offers a new practical in vitro guidance for monitoring an adequate dose of steroids in vivo.

Adrenal Cortex Hormones