We propose a molecular mechanism for the intra-cellular measurement of the ratio of the number of X chromosomes to the number of sets of autosomes, a process central to both sex determination and dosage compensation inDrosophila melanogaster. In addition to the two loci,da andSxl, which have been shown by Cline(Genetics, 90, 683, 1978)and others to be involved in these processes, we postulate two other loci, one autosomal (Ω) and the other, X-linked (π). The product of the autosomal locusda stimulates Ω and initiates synthesis of a limited quantity of repressor.Sxl and π ,both of which are X-linked, compete for this repressor as well as for RNA polymerase. It is assumed thatSxl has lower affinity than π for repressor as well as polymerase and that the binding of polymerase to one of these sites modulates the binding affinity of the other site for the enzyme. It can be shown that as a result of these postulated interactions transcription from theSxl site is proportional to the X/A ratio such that the levels ofSxl⁺ product are low in males, high in females and intermediate in the intersexes. If, as proposed by Cline, theSxl^- product is an inhibitor of X chromosome activity, this would result in dosage compensation. The model leads to the conclusion that high levels ofSxl⁺ product promote a female phenotype and low levels, a male phenotype. One interesting consequence of the assumptions on which the model is based is that the level ofSxl⁺ product in the cell, when examined as a function of increasing repressor concentration, first goes up and then decreases, yielding a bell-shaped curve. This feature of the model provides an explanation for some of the remarkable interactions among mutants at theSxl, da andmle loci and leads to several predictions. The proposed mechanism may also have relevance to certain other problems, such as size regulation during development, which seem to involve measurement of ratios at the cellular level.

Free-living amoebae of the cellular slime mouldDictyostelium discoideum aggregate when starved and give rise to a long and thin multicellular structure, the slug. The slug resembles a metazoan embryo, and as with other embryos it is possible to specify a fate map. In the case ofDictyostelium discoideum the map is especially simple: cells in the anterior fifth of the slug die and form a stalk while the majority of those in the posterior differentiate into spores. The genesis of this anterior-posterior distinction is the subject of our review. In particular, we ask: what are the relative roles of individual pre-aggregative predispositions and post-aggregative position in determining cell fate? We review the literature on the subject and conclude that both factors are important. Variations in nutritional status, or in cell cycle phase at starvation, can bias the probability that an amoeba differentiates into a stalk cell or a spore. On the other hand, isolates, or slug fragments, consisting of only prestalk cells or only prespore cells can regulate so as to result in a normal range of both cell types. We identify three levels of control, each being responsible for guiding patterning in normal development: (i) ‘coin tossing’, whereby a cell autonomously exhibits a preference for developing along either the stalk or the spore pathway with relative probabilities that can be influenced by the environment; (ii) ‘chemical kinetics’, whereby prestalk and prespore cells originate from undifferentiated amoebae on a probabilistic basis but, having originated, interact (e.g. via positive and negative feedbacks), and the interaction influences the possibility of conversion of one cell type into the other; and (iii) ‘positional information’, in which the spatial distribution of morphogens in the slug influences the pathway of differentiation. In the case of possibilities (i) and (ii), sorting out of like cell types leads to the final spatial pattern. In the case of possibility (iii), the pattern arisesin situ

We have shown previously that the Ca²⁺-specific fluorescent dyes chlortetracycline (CTC) and indo-1/AM can be used to distinguish between prestalk and prespore cells inDictyostelium discoideum at a very early stage. In the present study, pre-and post-aggregative amoebae ofDictyostelium discoideum were labelled with CTC or indo-1 and their fluorescence monitored after being drawn into a fine glass capillary. The cells rapidly form two zones of Ca²⁺-CTC or Ca²⁺-indo-1 fluorescence. Anterior (air side) cells display a high level of fluorescence; the level drops in the middle portion of the capillary and rises again to a lesser extent in the posteriormost cells (oil side). When bounded by air on both sides, the cells display high fluorescence at both ends. When oil is present at both ends of the capillary, there is little fluorescence except for small regions at the ends. These outcomes are evident within a couple of minutes of the start of the experiment and the fluorescence pattern intensifies over the course of time. By using the indicator neutral red, as well as with CTC and indo-1, we show that a band displaying strong fluorescence moves away from the anterior end before stabilizing at the anterior-posterior boundary. We discuss our findings in relation to the role of Ca²⁺ in cell-type differentiation inDictyostelium discoideum.

In a screen for calcium-regulated gene expression during growth and development ofDictyostelium discoideum we have identified an asparaginyl tRNA synthetase (ddAsnRS) gene, the second tRNA synthetase gene identified in this organism. TheddAsnRS gene shows many unique features. One, it is repressed by lowering cellular calcium, making it the first known calcium-regulated tRNA synthetase. Two, despite the calcium-dependence, its expression is unaltered during the cell cycle, making this the firstD. discoideum gene to show a calcium-dependent but cell cycle phase-independent expression. Finally, the N-terminal domain of the predicted ddAsnRS protein shows higher sequence similarity to Glutaminyl tRNA synthetases than to other Asn tRNA synthetases. These unique features of theAsnRS from this primitive eukaryote not only point to a novel mechanism regulating the components of translation machinery and gene expression by calcium, but also hint at a link between the evolution ofGlnRS andAsnRS in eukaryotes.

In the trishanku (triA⁻) mutant of the social amoeba Dictyostelium discoideum, aggregates are smaller than usual and the spore mass is located mid-way up the stalk, not at the apex. We have monitored aggregate territory size, spore allocation and fruiting body morphology in chimaeric groups of (quasi-wild-type) Ax2 and triA⁻ cells. Developmental canalisation breaks down in chimaeras and leads to an increase in phenotypic variation. A minority of triA⁻ cells causes largely Ax2 aggregation streams to break up; the effect is not due to the counting factor. Most chimaeric fruiting bodies resemble those ofAx2 or triA⁻. Others are double-deckers with a single stalk and two spore masses, one each at the terminus and midway along the stalk. The relative number of spores belonging to the two genotypes depends both on the mixing ratio and on the fruiting body morphology. In double-deckers formed from 1:1 chimaeras, the upper spore mass has more Ax2 spores, and the lower spore mass more triA⁻ spores, than expected. Thus, the traits under study depend partly on the cells’ own genotype and partly on the phenotypes, and so genotypes, of other cells: they are both autonomous and non-autonomous. These findings strengthen the parallels between multicellular development and behaviour in social groups. Besides that, they reinforce the point that a trait can be associated with a genotype only in a specified context.

Groups exhibit properties that either are not perceived to exist, or perhaps cannot exist, at the individual level. Such `emergent’ properties depend on how individuals interact, both among themselves and with their surroundings. The world of everyday objects consists of material entities. These are, ultimately, groups of elementary particles that organize themselves into atoms and molecules, occupy space, and so on. It turns out that an explanation of even the most commonplace features of this world requires relativistic quantum field theory and the fact that Planck’s constant is discrete, not zero. Groups of molecules in solution, in particular polymers (`sols’), can form viscous clusters that behave like elastic solids (`gels’). Sol-gel transitions are examples of cooperative phenomena. Their occurrence is explained by modelling the statistics of inter-unit interactions: the likelihood of either state varies sharply as a critical parameter crosses a threshold value. Group behaviour among cells or organisms is often heritable and therefore can evolve. This permits an additional, typically biological, explanation for it in terms of reproductive advantage, whether of the individual or of the group. There is no general agreement on the appropriate explanatory framework for understanding group-level phenomena in biology.

In Dictyostelium discoideum, cells that become part of the stalk or basal disc display behaviour that can be interpreted asaltruistic. Atzmony et al. (Curr Sci 72:142–145, 1997) had hypothesised that this behaviour could be the outcome of anadaptive strategy based on differing intrinsic quality as reflected by phenotypes that indicate differences in potential forsurvival and reproduction, followed by intercellular competition among amoebae of differing qualities. Low-qualityamoebae would have a poor chance of succeeding in the competition to form spores; they could enhance their chances ofsurvival by adopting a presumptive stalk strategy. Here we extend the hypothesis by making use of recent findings. Ourapproach is based on the view that an evolutionary explanation for the apparent altruism of stalk cells in D. discoideummust apply broadly to other cellular slime moulds (CSMs) that exhibit stalk cell death. Further, it must be capable of beingmodified to cover social behaviour in CSMs with an extracellular stalk, as well as in sorocarpic amoebae whose stalk cellsare viable. With regard to D. discoideum, we suggest that (a) differentiation-inducing factor, thought of as a signal thatinhibits amoebae from forming spores and induces them to differentiate into basal disc cells, is better viewed as a mediatorof competition among post-aggregation amoebae and (b) the products of the ‘recognition genes’, tgrB and tgrC, allow anamoeba to assess its quality relative to that of its neighbours and move to a position within the aggregate that optimises itsreproductive fitness. From this perspective, all cells behave in a manner that is ‘selfish’ rather than ‘altruistic’, albeit withdifferent expectations of success.