Chromosome-scale selective sweeps shape Caenorhabditis elegans genomic diversity

The nematode Caenorhabditis elegans is central to research in molecular, cell and developmental biology, but nearly all of this research has been conducted on a single strain of C. elegans. Little is known about the population genomic and evolutionary history of this species. We characterized C. elegans genetic variation using high-throughput selective sequencing of a worldwide collection of 200 wild strains and identified 41,188 SNPs. Notably, C. elegans genome variation is dominated by a set of commonly shared haplotypes on four of its six chromosomes, each spanning many megabases. Population genetic modeling showed that this pattern was generated by chromosome-scale selective sweeps that have reduced variation worldwide; at least one of these sweeps probably occurred in the last few hundred years. These sweeps, which we hypothesize to be a result of human activity, have drastically reshaped the global C. elegans population in the recent past.     

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.     

Single-copy insertion of transgenes in Caenorhabditis elegans

At present, transgenes in Caenorhabditis elegans are generated by injecting DNA into the germline. The DNA assembles into a semistable extrachromosomal array composed of many copies of injected DNA. These transgenes are typically overexpressed in somatic cells and silenced in the germline. We have developed a method that inserts a single copy of a transgene into a defined site. Mobilization of a Mos1 transposon generates a double-strand break in noncoding DNA. The break is repaired by copying DNA from an extrachromosomal template into the chromosomal site. Homozygous single-copy insertions can be obtained in less than 2 weeks by injecting approximately 20 worms. We have successfully inserted transgenes as long as 9 kb and verified that single copies are inserted at the targeted site. Single-copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines.     

Exploiting Spillovers to Forecast Crashes

We develop Hawkes models in which events are triggered through self‐excitation as well as cross‐excitation. We examine whether incorporating cross‐excitation improves the forecasts of extremes in asset returns compared to only self‐excitation. The models are applied to US stocks, bonds and dollar exchange rates. We predict the probability of crashes in the series and the value at risk (VaR) over a period that includes the financial crisis of 2008 using a moving window. A Lagrange multiplier test suggests the presence of cross‐excitation for these series. Out‐of‐sample, we find that the models that include spillover effects forecast crashes and the VaR significantly more accurately than the models without these effects. Copyright © 2016 John Wiley & Sons, Ltd.     

Carl du Prel (1839–1899): explorer of dreams, the soul, and the cosmos

Nineteenth-century spiritism was a blend of religious elements, the philosophy of mind, science and popular science and contacts with extraterrestrials were a commonplace phenomenon during spiritistic séances. Using the example of Carl du Prel (1839–1899) I show how his comprehensive mystic philosophy originated in a theory of extraterrestrial life. Carl du Prel used a Darwinian and monistic framework, theories of the unconscious and a Neo-Kantian epistemology to formulate a philosophy of astronomy and extraterrestrial life. He claimed that the mechanism of Darwinian selection is responsible for the distribution of stars and the orbits of the planets. In his speculations on the nature of extraterrestrial life he used the concept of organ projection to argue that technical solutions on earth will be realized organically on other planets and claimed that superior extraterrestrials have quantitatively and qualitatively different senses and thus different forms of intuition. A comparison with Camille Flammarion, spiritist and populariser of astronomy, demonstrates the contextual complexities of spiritism. In contrast to du Prel’s sober Neo-Kantian philosophical speculations, Flammarion was a late proponent of a French esoteric tradition that was rooted in romantic socialism, painted grand cosmological vistas and emphasized reincarnation. I put forward the hypothesis that current discourses on extraterrestrial life are affected by the spiritist tradition mainly through the ‘Golden Age’ science fiction literature of the 1940s and 50s and its successors. However, neither Carl du Prel nor Camille Flammarion contributed significantly to this tradition, which is mainly shaped by the psychical research of J. B. Rhine.     

Generation time and temporal scaling of bird population dynamics

Theoretical studies have shown that variation in density regulation strongly influences population dynamics, yet our understanding of factors influencing the strength of density dependence in natural populations still is limited. Consequently, few general hypotheses have been advanced to explain the large differences between species in the magnitude of population fluctuations. One reason for this is that the detection of density regulation in population time series is complicated by time lags induced by the life history of species that make it difficult to separate the relative contributions of intrinsic and extrinsic factors to the population dynamics. Here we use population time series for 23 bird species to estimate parameters of a stochastic density-dependent age-structured model. We show that both the strength of total density dependence in the life history and the magnitude of environmental stochasticity, including transient fluctuations in age structure, increase with generation time. These results indicate that the relationships between demographic and life-history traits in birds translate into distinct population dynamical patterns that are apparent only on a scale of generations.     

Mapping determinants of human gene expression by regional and genome-wide association

To study the genetic basis of natural variation in gene expression, we previously carried out genome-wide linkage analysis and mapped the determinants of approximately 1,000 expression phenotypes. In the present study, we carried out association analysis with dense sets of single-nucleotide polymorphism (SNP) markers from the International HapMap Project. For 374 phenotypes, the association study was performed with markers only from regions with strong linkage evidence; these regions all mapped close to the expressed gene. For a subset of 27 phenotypes, analysis of genome-wide association was performed with >770,000 markers. The association analysis with markers under the linkage peaks confirmed the linkage results and narrowed the candidate regulatory regions for many phenotypes with strong linkage evidence. The genome-wide association analysis yielded highly significant results that point to the same locations as the genome scans for about 50% of the phenotypes. For one candidate determinant, we carried out functional analyses and confirmed the variation in cis-acting regulatory activity. Our findings suggest that association studies with dense SNP maps will identify susceptibility loci or other determinants for some complex traits or diseases.     

Mapping the Hawaiian plume conduit with converted seismic waves

The volcanic edifice of the Hawaiian islands and seamounts, as well as the surrounding area of shallow sea floor known as the Hawaiian swell, are believed to result from the passage of the oceanic lithosphere over a mantle hotspot. Although geochemical and gravity observations indicate the existence of a mantle thermal plume beneath Hawaii, no direct seismic evidence for such a plume in the upper mantle has yet been found. Here we present an analysis of compressional-to-shear (P-to-S) converted seismic phases, recorded on seismograph stations on the Hawaiian islands, that indicate a zone of very low shear-wave velocity (< 4 km s(-1)) starting at 130-140 km depth beneath the central part of the island of Hawaii and extending deeper into the upper mantle. We also find that the upper-mantle transition zone (410-660 km depth) appears to be thinned by up to 40-50 km to the south-southwest of the island of Hawaii. We interpret these observations as localized effects of the Hawaiian plume conduit in the asthenosphere and mantle transition zone with excess temperature of approximately 300 degrees C. Large variations in the transition-zone thickness suggest a lower-mantle origin of the Hawaiian plume similar to the Iceland plume, but our results indicate a 100 degrees C higher temperature for the Hawaiian plume.     

Kinetics of BRCA1 regulation in response to UVC radiation

To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed an increase in BRCA1 protein levels above 78 J/m². This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1 after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4 h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene. Received 6 April 2000; received after revision 23 May 2000; accepted 23 May 2000