Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

Developmental and acclimatory contributions to water loss in a desert rodent: investigating the time course of adaptive change

Understanding the evolution of physiological traits requires considering three nonexclusive mechanisms that underlie phenotypes and cause their change over different time scales: acclimation, developmental plasticity, and natural selection for genetically fixed traits. Physiological adjustments to changes in the desiccating potential of the environment were investigated with one subspecies of common desert rodent, Dipodomys merriami merriami (Merriam's kangaroo rat). We raised young whose parents originated from environments that differ in both temperature and humidity. These young were raised under either desiccating or water-abundant conditions, and their water loss was measured at a series of temperatures to determine the effect developmental conditions have on resistance to desiccation. We then determined the contribution of acclimation to desiccation resistance by keeping the differentially raised young in conditions opposite to those during their development and again measuring water loss. We found that developmental plasticity and acclimation can completely account for the existing intraspecific variability in desiccation resistance under certain conditions. In fact, developmental and acclimatory changes can equal genetically based differences of the populations. This phenotypic plasticity can operate relatively quickly and therefore may attenuate the actions of natural selection. Understanding the extent and nature of such flexibility is critical to our understanding intraspecific variability and the consequences of changing climate.     

Nutritional Aspects of Dissimilatory Sulfate Reduction in the Human Large Intestine

In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group.  Experiments with two strains of Desulfovibrio desulfuricans isolated from human feces demonstrated that both were able to reduce sulfite, thiosulfate or nitrate in the absence of sulfate. In addition, one strain (DsvUC1) was able to grow by fermentative metabolism, although the second strain (DsvFD1) showed more restricted fermentative growth. The data indicate that desulfovibrios are ecologically the most significant group of SRB in the human colon, and that colonic isolates belonging to this genus are versatile, in terms of both the electron acceptors and donors that they are able to utilize. Received: 24 March 1997 / Accepted: 10 June 1997     

Infra-red Thermography for High Throughput Field Phenotyping in Solanum tuberosum

The rapid development of genomic technology has made high throughput genotyping widely accessible but the associated high throughput phenotyping is now the major limiting factor in genetic analysis of traits. This paper evaluates the use of thermal imaging for the high throughput field phenotyping of Solanum tuberosum for differences in stomatal behaviour. A large multi-replicated trial of a potato mapping population was used to investigate the consistency in genotypic rankings across different trials and across measurements made at different times of day and on different days. The results confirmed a high degree of consistency between the genotypic rankings based on relative canopy temperature on different occasions. Genotype discrimination was enhanced both through normalising data by expressing genotype temperatures as differences from image means and through the enhanced replication obtained by using overlapping images. A Monte Carlo simulation approach was used to confirm the magnitude of genotypic differences that it is possible to discriminate. The results showed a clear negative association between canopy temperature and final tuber yield for this population, when grown under ample moisture supply. We have therefore established infrared thermography as an easy, rapid and non-destructive screening method for evaluating large population trials for genetic analysis. We also envisage this approach as having great potential for evaluating plant response to stress under field conditions.     

Minimizing Cognitive Errors in Site-Specific Causal Assessments

Interest in causal investigations in aquatic systems has been a natural outgrowth of the increased use of biological monitoring to characterize the condition of resources. Although biological monitoring approaches are critical tools for detecting whether effects are occurring, they do not identify the cause of the observed effects. Formal approaches to causal evaluation can provide a mechanism to build on expert knowledge, increasing the likelihood that remedial efforts will achieve the desired environmental improvement. This paper examines how formal approaches to causal investigations minimize common errors. We reviewed common cognitive errors reported in the literature, and compared them with considerations suggested for strength-of-evidence approaches. Many of the causal considerations are directed toward distinguishing spurious correlations from true causal relationships. However, this is only one type of error; others include hypothesis dependence, confirmation bias, hypothesis tenacity and anchoring. We suggest three general principles for minimizing error in site-specific investigations: (1) Conduct the causal evaluation as a fair, transparent comparison among alternatives; (2) Carefully describe and quantify the conjunction of cause and effect; and (3) Consider that conjunction between cause and effect is spurious, or that a real conjunction was masked.     

Tight linkage of pyruvate kinase (PKLR) and glucocerebrosidase (GBA) genes

Two polymorphisms, one in the liver-type pyruvate kinase gene (PKLR) and one in the glucocerebrosidase gene (GBA), both of which are on band q21 of chromosome 1, were found to be tightly linked. Each of three Gaucher disease mutations in 112 chromosomes studied was associated with a unique haplotype. With a conservative assumption about the length of time that the Gaucher disease mutation has been present in the Jewish population, we deduce that the genetic distance between these two loci is probably under 0.2 centimorgans. Four haplotypes are produced by these polymorphic loci, but two of these are relatively uncommon because the polymorphic sites are in linkage disequilibrium. Nonetheless these markers are potentially useful in the prenatal diagnosis of pyruvate kinase deficiency in families who have at least one affected child and may also be helpful in heterozygote detection in families with Gaucher disease where a specific mutation producing the disease in unknown.