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Biomedical subjects

Stephen C Pratt

Publications and source records attributed to Stephen C Pratt.

5 recordsLinked to original sources

Global mapping of transposon location.

Transposable genetic elements are ubiquitous, yet their presence or absence at any given position within a genome can vary between individual cells, tissues, or strains. Transposable elements have profound impacts on host genomes by altering gene expression, assisting in genomic rearrangements, causing insertional mutations, and serving as sources of phenotypic variation. Characterizing a genome's full complement of transposons requires whole genome sequencing, precluding simple studies of the impact of transposition on interindividual variation. Here, we describe a global mapping approach for identifying transposon locations in any genome, using a combination of transposon-specific DNA extraction and microarray-based comparative hybridization analysis. We use this approach to map the repertoire of endogenous transposons in different laboratory strains of Saccharomyces cerevisiae and demonstrate that transposons are a source of extensive genomic variation. We also apply this method to mapping bacterial transposon insertion sites in a yeast genomic library. This unique whole genome view of transposon location will facilitate our exploration of transposon dynamics, as well as defining bases for individual differences and adaptive potential.

Chromosome Mapping↗

A tunable algorithm for collective decision-making.

Complex biological systems are increasingly understood in terms of the algorithms that guide the behavior of system components and the information pathways that link them. Much attention has been given to robust algorithms, or those that allow a system to maintain its functions in the face of internal or external perturbations. At the same time, environmental variation imposes a complementary need for algorithm versatility, or the ability to alter system function adaptively as external circumstances change. An important goal of systems biology is thus the identification of biological algorithms that can meet multiple challenges rather than being narrowly specified to particular problems. Here we show that emigrating colonies of the ant Temnothorax curvispinosus tune the parameters of a single decision algorithm to respond adaptively to two distinct problems: rapid abandonment of their old nest in a crisis and deliberative selection of the best available new home when their old nest is still intact. The algorithm uses a stepwise commitment scheme and a quorum rule to integrate information gathered by numerous individual ants visiting several candidate homes. By varying the rates at which they search for and accept these candidates, the ants yield a colony-level response that adaptively emphasizes either speed or accuracy. We propose such general but tunable algorithms as a design feature of complex systems, each algorithm providing elegant solutions to a wide range of problems.

Algorithms↗

Population genomic analysis of outcrossing and recombination in yeast.

The budding yeast Saccharomyces cerevisiae has been used by humans for millennia to make wine, beer and bread. More recently, it became a key model organism for studies of eukaryotic biology and for genomic analysis. However, relatively little is known about the natural lifestyle and population genetics of yeast. One major question is whether genetically diverse yeast strains mate and recombine in the wild. We developed a method to infer the evolutionary history of a species from genome sequences of multiple individuals and applied it to whole-genome sequence data from three strains of Saccharomyces cerevisiae and the sister species Saccharomyces paradoxus. We observed a pattern of sequence variation among yeast strains in which ancestral recombination events lead to a mosaic of segments with shared genealogy. Based on sequence divergence and the inferred median size of shared segments (approximately 2,000 bp), we estimated that although any two strains have undergone approximately 16 million cell divisions since their last common ancestor, only 314 outcrossing events have occurred during this time (roughly one every 50,000 divisions). Local correlations in polymorphism rates indicate that linkage disequilibrium in yeast should extend over kilobases. Our results provide the initial foundation for population studies of association between genotype and phenotype in S. cerevisiae.

Crosses, Genetic↗

Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray.

A central challenge of genomics is to detect, simply and inexpensively, all differences in sequence among the genomes of individual members of a species. We devised a system to detect all single-nucleotide differences between genomes with the use of data from a single hybridization to a whole-genome DNA microarray. This allowed us to detect a variety of spontaneous single-base pair substitutions, insertions, and deletions, and most (>90%) of the approximately 30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae strains. We applied this approach to elucidate the genetic basis of phenotypic variants and to identify the small number of single-base pair changes accumulated during experimental evolution of yeast.

Directed Molecular Evolution↗

Information flow, opinion polling and collective intelligence in house-hunting social insects.

The sharing and collective processing of information by certain insect societies is one of the reasons that they warrant the superlative epithet 'super-organisms' (Franks 1989, Am. Sci. 77, 138-145). We describe a detailed experimental and mathematical analysis of information exchange and decision-making in, arguably, the most difficult collective choices that social insects face: namely, house hunting by complete societies. The key issue is how can a complete colony select the single best nest-site among several alternatives? Individual scouts respond to the diverse information they have personally obtained about the quality of a potential nest-site by producing a recruitment signal. The colony then deliberates over (i.e. integrates) different incoming recruitment signals associated with different potential nest-sites to achieve a well-informed collective decision. We compare this process in honeybees and in the ant Leptothorax albipennis. Notwithstanding many differences - for example, honeybee colonies have 100 times more individuals than L. albipennis colonies - there are certain similarities in the fundamental algorithms these societies appear to employ when they are house hunting. Scout honeybees use the full power of the waggle dance to inform their nest-mates about the distance and direction of a potential nest-site (and they indicate the quality of a nest-site indirectly through the vigour of their dance), and yet individual bees perhaps only rarely make direct comparisons of such sites. By contrast, scouts from L. albipennis colonies often compare nest-sites, but they cannot directly inform one another of their estimation of the quality of a potential site. Instead, they discriminate between sites by initiating recruitment sooner to better ones. Nevertheless, both species do make use of forms of opinion polling. For example, scout bees that have formerly danced for a certain site cease such advertising and monitor the dances of others at random. That is, they act without prejudice. They neither favour nor disdain dancers that advocate the site they had formerly advertised or the alternatives. Thus, in general the bees are less well informed than they would be if they systematically monitored dances for alternative sites rather than spending their time reprocessing information they already have. However, as a result of their lack of prejudice, less time overall will be wasted in endless debate among stubborn and potentially biased bees. Among the ants, the opinions of nest-mates are also pooled effectively when scouts use a threshold population of their nest-mates present in a new nest-site as a cue to switch to more rapid recruitment. Furthermore, the ants' reluctance to begin recruiting to poor nest-sites means that more time is available for the discovery and direct comparison of alternatives. Likewise, the retirement of honeybee scouts from dancing for a given site allows more time for other scouts to find potentially better sites. Thus, both the ants and the bees have time-lags built into their decision-making systems that should facilitate a compromise between thorough surveys for good nest-sites and relatively rapid decisions. We have also been able to show that classical mathematical models can illuminate the processes by which colonies are able to achieve decisions that are relatively swift and very well informed.

Animal Communication↗