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Pervasive fitness trade-offs revealed by rapid adaptation to shifting population densities in large experimental populations of Drosophila melanogaster.

Trade-offs are an inherent feature of organismal biology that are expected play a fundamental role in the evolution of natural populations. Efforts to quantify trade-offs are largely confined to phenotypic measurements and the identification of negative genetic-correlations among fitness-relevant traits. Here, we use time-series genomic data collected during experimental evolution in large, genetically diverse populations of Drosophila melanogaster to directly measure the manifestation of trade-offs in response to fluctuating selection on ecological timescales. Specifically, we first conducted a lab-based selection experiment to quantify a genome-wide signal of antagonistic pleiotropy elicited in response to shifting population densities and associated with reproduction and stress tolerance selection. In doing so, we identified a putative role of two cosmopolitan inversions in these trade-offs. We then conducted an independent experiment to show that a simple manipulation of increasing population density under controlled lab-based conditions identified loci that are relevant to selection during population expansion and collapse in a complex, semi-natural setting. In concert, our results reveal how adaptation in complex, natural environments can be coarse-grained in such a manner to drive repeatable and predictable patterns of genomic variation, and further add credence to models positing a role of generic fitness trade-offs in the maintenance of variation in natural populations.

Drosophila melanogaster

A graph analysis of the relationship between population density and social pathology.

This article deals with systematic variables--population density and pathological effects--at the level of a community or organizational system. Existing studies of the relationship between population density and social pathology (e.g., mortality, mental illness) in humans have failed to determine a strictly causal relationship between density and pathology in a linear model. They have not established a direct link between density and pathology in a simple two-variable, linear causal approach. Eliminating other variables by statistical control has obscured the conditions of a complex phenomenon. By incorporating socioeconomic variables into a general system model, this paper suggests that the total configuration of social organization, adaptation, previous group experience, and environment determine the effects of population density. Using a method of graph analysis, a model is presented of the relationship between population density and social pathology which has a high degree of isomorphism with the empirical situation.

Adrenocorticotropic Hormone

The effects of genotype frequency and population density on fitness differentials in Escherichia coli.

Two strains of Escherichia coli K-12, a lac+ wild type and a lac- auxotroph, were grown both as pure and mixed cultures, using a serial transfer procedure. Four different growth media were employed, consisting of the same minimal salts solution, but different total concentrations of the sugars lactose, arabinose, and glucose (in proportions 5:4:1). Population densities and genotypic frequencies were assayed every 48 hours, at the time of transfer. Population density of the pure lac+ culture was greater than that of the pure lac- culture for all media; this was expected, since the latter cannot utilize lactose. Mixed cultures quickly approached the same density as the corresponding lac+ controls, and the frequency of the lac+ genotype increased steadily for all media. Trajectories of lambda = log (P divided by Q) were strictly nonlinear, indicating a dependence of the selective differential on population density and genotypic frequency. The rate of substitution decreased slightly with increasing sugar concentration, contrary to theoretical expectation. It was speculated that either the generation interval was longer for denser cultures (higher substrate concentrations) of that buildup of organic by-products reduced the selective differential in denser cultures. For a single medium, however, the behavior of completing genotypic strains was reasonably well predicted by theoretical models of frequency and density-dependent selection, the parameters of which may be related to the experimental inputs.

Culture Media

Chinese hamster ovary cell population density affects intracellular concentrations of calcium-dependent regulator and ability of regulator to inhibit adenylate cyclase activity.

The adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of crude Chinese hamster ovary cell membranes was inhibited 30-40% by low concentrations (6-600 ng/ml) of calcium-dependent regulator (CDR). This inhibitory effect was lost at concentrations of CDR above 600 ng/ml. The adenylate cyclase activity of membranes prepared from low population density Chinese hamster ovary cells was not appreciably altered by CDR. However, with increasing cell population density there was a significant increase in the ability of CDR to inhibit cyclic AMP formation. Further, the intracellular levels of CDR determined in the 12,000 x g supernatant and particulate fractions varied inversely with increasing cell population density. As cell number increased from 2 x 10(6) to 10 x 10(6) cells per dish the CDR concentration present in the supernatant fraction increased from 0.4 to 0.8 mug of CDR per mg of protein, while the amount of endogenous CDR associated with the particulate fraction decreased from 0.6 to 0.4 mug of CDR per mg of protein. This suggests that possible changes in the distribution of CDR between the supernatant and membrane fractions might serve as a regulatory mechanism for activities under CDR control.

3',5'-Cyclic-AMP Phosphodiesterases

The estimation of neuronal population density by a robust distance method.

A new "nearest-neighbour" or "distance" method of estimating neurone population density is introduced. The method was originally developed for ecological studies but can be imported into histology without significant modification; changes in population density can be estimated by inverting the measure of area per unit cell (the so-called mean area). Its advantages include tests of randomness for the spatial distribution of the cells at issue and a robustness which can tolerate some departure from a random distribution pattern. To illustrate how the method is applied estimates of neurone density, in terms of "mean area" per cell-point, are made on a montage tracing of the human cerebellar dentate nucleus.

Cell Count

Fucolipid metabolism as a function of cell population density in normal and murine sarcoma virus-transformed rat cells.

The incorporation of isotopically labeled fucose into the lipids of normal and murine sarcoma virus-transformed rat cells as a function of cell population density was examined. When normal cells were seeded at low cell density, the levels of the major fucolipids, i.e., fucolipids III and IV, were substantially reduced, but then they increased as the cells approached confluency. This variation in synthesis of fucolipids III and IV appeared to be primarily related to cell density and not to cell growth. Chase experiments revealed that the reduced level of fucolipids III and IV in sparse normal cells is due to decreased synthesis rather than to increased catabolism. In contrast to the observations with normal rat cells, the high level of fucolipid III and the low level of fucolipid IV in murine sarcoma virus-transformed rat cells was shown to be independent of cell population density.

Animals

Mast cell population density, blood vessel density and histamine content in normal human skin.

Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites. Mast cell and blood vessel counts were made in 1--1.5 micrometer thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorimetric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject.

Adult

Population density as a factor in the evolution of neoplastic cell lines.

The influence of population density in the progression from the nonneoplastic to the neoplastic state has been reassessed. Two twice-cloned, nonneoplastic mouse lines, NCTC 7914 and 7915, were transferred each 3 to 4 days at inoculum sizes selected to minimize or maximize cell-cell contact, 1 X 10(5) or 4 X 10(5) cells/T-15, respectively. As tested by in vivo assay, the regime designed to minimize cell-cell contact did not reproducibly delay transformation, and tumor production was observed in all lines, irrespective of inoculum size. Also, results of tumorigenesis assays correlated with blind evaluation of morphological and cytological alterations, growth in agarose, and susceptibility to killing by activated macrophages. Generally higher saturation densities were seen as a function of period in culture, and no significant differences in glucose utilization or lactic acid production were observed between nonneoplastic and neoplastic cell populations.

BCG Vaccine

Mangabey(Cercocebus albigena). Social organization and population density in relation to food use and availability.

Data are presented on the feeding behavior and activities of mangabeys (Cercocebus albigena) in the Ngogo study area, Kibale Forest, Uganda. Mangabeys spend 47% of activity observations feeding, 27% moving, and the remainder of the activity observations is accounted for by grooming, playing, vocalizing, copulating, etc. Feeding on fruit constitutes 58% of feeding records, arthropods 25%, young leaves and flowers 10%, cambium 5% and rare and unidentified items 2%. 29 tree species are used as sources of vegetable food and 31 tree species are used as substrate for arthropod search. Mangabeys move an average distance of 1,299 m per day, and use an average of 28,50 X 50 m quadrats per day. The activity patterns, the types and number of food species, the daily distances traveled, and the number of quadrats used per day, are not significantly different from those found in the literature for mangabeys in the Kanyawara research area, Kibale Forest, Uganda. Mangabey population density in Ngogo is approximately 1.46 times that of the Kanyawara mangabeys. The difference in density is associated with Ngogo exhibiting a greater mangabey food tree density than is found at Kanyawara. The higher mangabey density in Ngogo is associated with an average group size similar to that at Kanyawara, and an increase in the number of groups per unit area. The greater number of groups is accommodated by the mangabey having smaller home ranges, and less home range overlap than do the Kanyawara mangabeys. I suggest that these results are compatible with an interpretation based on disease control via regulation of group size, and social and spatial isolation between groups. The role of food availability in regulation of group size, or determining land tenure systems remains uncertain.

Animals

Degradation of blood group antigens in human colon ecosystems. II. A gene interaction in man that affects the fecal population density of certain enteric bacteria.

The autosomal dominant ABH secretor gene together with the ABO blood type gene control the presence and specificity of A, B, and H blood group antigens in human gut mucin glycoproteins. Certain obligate anaerobes in feces produce extracellular antigen-specific glycoside structures. We estimated the populations of these bacteria in feces of 22 healthy subjects by determining the greatest dilution of feces that yielded A, B, or H blood group-degrading enzyme activity after 24 h incubation in anaerobic cultures. Comparatively small populations of fecal bacteria produce blood group-degrading enzymes; their estimated populations were 10(8) per g or less in 21 subjects. Fecal populations of B-degrading bacteria were stable over time, and their population density averaged 50,000-fold greater in blood group B secretros than in other subjects. We present evidence that the greater fecal populations of B-degrading bacteria in B secretors is due in part to a competitive nutritional advantage gained by their ability to enzymatically cleave the B antigenic determinant alpha-D-galactose from gut mucins of B secretors. Fecal populations of bacteria producing A and H antigen-degrading enzyme activities were comparable in all subjects to the fecal population of B-degrading bacteria in B secretors. The large populations of fecal anaerobes may be an additional source of A antigen substrate for A-degrading bacteria; thus, antigens cross-reacting with A antigen were detected on cell walls of anaerobic bacteria from 3 of 10 cultures inoculated with 10(-10) g feces. Bacteria producing B-degrading activity likely represent a separate population from those producing A- or H-degrading activity since their fecal populations differed numerically in 14 subjects. These findings suggest that adaptation of blood group-degrading enzymes to mucin structures in human colon ecosystems is chiefly by mutation-selection of comparatively small populations of constitutive enzyme-producing strains rather than by substrate induced enzyme synthesis in many strains.

ABO Blood-Group System

A method for the regulation of microbial population density during continuous culture at high growth rates.

A method for the continuous culture of microorganisms is described which employs growth-dependent pH changes to control the rate of addition of fresh medium to a culture vessel. The apparatus (the "phauxostat") supports, at constant pH, long-term continuous culture at rates near or at the maximum of which the organisms are capable. The buffering capacity of the inflowing medium determines the steady-state population density of the culture, but the rate of growth is independent of the buffering capacity. The fundamental theory of operation is tested and some basic parameters of growth are estimated using Escherichia coli B growing continuously in media containing glucose, glycerol or DL-lactate.

Bacteria