Error-prone polymerase activity causes multinucleotide mutations in humans

About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1,092 human genomes, demonstrating that MNMs become enriched as large numbers of individuals are sampled. We leverage the size of the dataset to deduce new information about the allelic spectrum of MNMs, estimating the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between the affected sites and showing that MNMs exhibit a high percentage of transversions relative to transitions. These findings are reproducible in data from multiple sequencing platforms. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived dinucleotides, with $\textrm{GC}\to \textrm{AA}$, $\textrm{GA}\to \textrm{TT}$ and their reverse complements making up 36% of the total. These same mutations dominate the spectrum of tandem mutations produced by the upregulation of low-fidelity Polymerase $\zeta$ in mutator strains of S. cerevisiae that have impaired DNA excision repair machinery. This suggests that low-fidelity DNA replication by Pol $\zeta$ is at least partly responsible for the MNMs that are segregating in the human population, and that useful information about the biochemistry of MNM can be extracted from ordinary population genomic data. We incorporate our findings into a mathematical model of the multinucleotide mutation process that can be used to correct phylogenetic and population genetic methods for the presence of MNMs

Decoding coalescent hidden Markov models in linear time

In many areas of computational biology, hidden Markov models (HMMs) have been used to model local genomic features. In particular, coalescent HMMs have been used to infer ancient population sizes, migration rates, divergence times, and other parameters such as mutation and recombination rates. As more loci, sequences, and hidden states are added to the model, however, the runtime of coalescent HMMs can quickly become prohibitive. Here we present a new algorithm for reducing the runtime of coalescent HMMs from quadratic in the number of hidden time states to linear, without making any additional approximations. Our algorithm can be incorporated into various coalescent HMMs, including the popular method PSMC for inferring variable effective population sizes. Here we implement this algorithm to speed up our demographic inference method diCal, which is equivalent to PSMC when applied to a sample of two haplotypes. We demonstrate that the linear-time method can reconstruct a population size change history more accurately than the quadratic-time method, given similar computation resources. We also apply the method to data from the 1000 Genomes project, inferring a high-resolution history of size changes in the European population.Comment: 18 pages, 5 figures. To appear in the Proceedings of the 18th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2014). The final publication is available at link.springer.co

Q&A: where did the Neanderthals go?

Abstract Genomic evidence has demonstrated that humans and Neanderthals interbred. Today, the genomes of most individuals outside Africa contain 2–3% Neanderthal DNA. However, it is still hotly debated why the Neanderthals went extinct and if humans contributed to the Neanderthal extinction. In this Q&A we explore what genomic data might have to say about this issue

Spitzer Observations of Spacecraft Target 162173 (1999 JU3)

Near-Earth asteroid 162173 (1999 JU3) is the primary target of the Hayabusa-2 sample return mission, and a potential target of the Marco Polo sample return mission. Earth-based studies of this object are fundamental to these missions. We present a mid-infrared spectrum (5-38 microns) of 1999 JU3 obtained with NASA's Spitzer Space Telescope in May 2008. These observations place new constraints on the surface properties of this asteroid. To fit our spectrum we used the near-Earth asteroid thermal model (NEATM) and the more complex thermophysical model (TPM). However, the position of the spin-pole, which is uncertain, is a crucial input parameter for constraining the thermal inertia with the TPM; hence, we consider two pole orientations. In the extreme case of an equatorial retrograde geometry we derive a lower limit to the thermal inertia of 150 J/m^2/K/s^0.5. If we adopt the pole orientation of Abe et al. (2008a) our best-fit thermal model yields a value for the thermal inertia of 700+/-200 J/m^2/K/s^0.5 and even higher values are allowed by the uncertainty in the spectral shape due to the absolute flux calibration. The lower limit to the thermal inertia, which is unlikely but possible, would be consistent with a fine regolith similar to wthat is found for asteroid 433 Eros. However, the thermal inertia is expected to be higher, possibly similar to or greater than that on asteroid 25143 Itokawa. Accurately determining the spin-pole of asteroid 162173 will narrow the range of possible values for its thermal inertia.Comment: 4 pages, 2 figures; to be published as a Letter in Astronomy and Astrophysic

Cultural Resources Investigations for the Proposed Espada Road Widening Project City of San Antonio Bexar County, Texas

Between February 2014 and October 2015, Atkins North America, Inc. (Atkins), conducted cultural resources investigations for the City of San Antonio’s (COSA’s) proposed Espada Road Widening Project. The project area extends from Southeast Interstate Loop 410 to approximately 137 meters (450 feet) west of the intersection of East Ashley Road and Espada Road, a distance of approximately 1.6 kilometers (1.0 mile), comprising 7.99 acres (3.2 hectares). The project area was subjected to an intensive pedestrian survey, which was supplemented by mechanical trenching. In total, 27 shovel tests and 9 backhoe trenches were placed in locations across the Area of Potential Effects (APE), with particular emphasis on areas potentially containing remnants of distribution laterals extending from the Espada Acequia. Although the locations of a few of the acequia laterals were visible from the surface, most have been backfilled and affected by modern disturbances. Mechanical trenching was employed in an attempt to catch the acequia laterals in cross-section, but no such features were observed. No new archaeological resources were identified during the survey. An archival review hypothesized the presence of three acequia laterals extending into the parcel immediately south of Rilling Road. Because the property currently houses a construction yard and no excavation was possible, the parcel could not be examined at the time of the surveys. Therefore, Atkins recommends that any construction within that section of the APE be monitored by a qualified archaeologist. Atkins also recommends monitoring the property at the northern end of Espada Road, where an outfall will be located. Due to the APE’s proximity to existing archaeological site 41BX260 at that location, excavation within that portion of the APE should be monitored as well

Optical fiber tips functionalized with semiconductor photonic crystal cavities

We demonstrate a simple and rapid epoxy-based method for transferring photonic crystal cavities to the facets of optical fibers. Passive Si cavities were measured via fiber taper coupling as well as direct transmission from the fiber facet. Active quantum dot containing GaAs cavities showed photoluminescence that was collected both in free space and back through the original fiber. Cavities maintain a high quality factor (2000-4000) in both material systems. This new design architecture provides a practical mechanically stable platform for the integration of photonic crystal cavities with macroscale optics and opens the door for novel research on fiber-coupled cavity devices.Comment: 10 pages, 5 figure

Formation of atypical podosomes in extravillous trophoblasts regulates extracellular matrix degradation

Throughout pregnancy the cytotrophoblast, the stem cell of the placenta, gives rise to the differentiated forms of trophoblasts. The two main cell lineages are the syncytiotrophoblast and the invading extravillous trophoblast. A successful pregnancy requires extravillous trophoblasts to migrate and invade through the decidua and then remodel the maternal spiral arteries. Many invasive cells use specialised cellular structures called invadopodia or podosomes in order to degrade extracellular matrix. Despite being highly invasive cells, the presence of invadapodia or podosomes has not previously been investigated in trophoblasts. In this study these structures have been identified and characterised in extravillous trophoblasts. The role of specialised invasive structures in trophoblasts in the degradation of the extracellular matrix was compared with well characterised podosomes and invadopodia in other invasive cells and the trophoblast specific structures were characterised by using a sensitive matrix degradation assay which enabled visualisation of the structures and their dynamics. We show trophoblasts form actin rich protrusive structures which have the ability to degrade the extracellular matrix during invasion. The degradation ability and dynamics of the structures closely resemble podosomes, but have unique characteristics that have not previously been described in other cell types. The composition of these structures does not conform to the classic podosome structure, with no distinct ring of plaque proteins such as paxillin or vinculin. In addition, trophoblast podosomes protrude more deeply into the extracellular matrix than established podosomes, resembling invadopodia in this regard. We also show several significant pathways such as Src kinase, MAPK kinase and PKC along with MMP-2 and 9 as key regulators of extracellular matrix degradation activity in trophoblasts, while podosome activity was regulated by the rigidity of the extracellular matrix

Library Staff Salary Survey Report: A First Thursday Presentation

This presentation was given by the Salary Task Force (STF) members, Jamie Rogers, Annia Gonzalez, and Kelley Rowan at an FIU Libraries First Thursday\u27s Forum. Members of the task force presented the results from two surveys, including cost of living research and SUS salary analysis and comparisons. Afterwards, attendees were invited to ask questions and express their concerns before the task force publishes the final report. The research in this presentation is based on surveys and research conducted by all Salary Task Force members