Extreme Scale De Novo Metagenome Assembly

Metagenome assembly is the process of transforming a set of short, overlapping, and potentially erroneous DNA segments from environmental samples into the accurate representation of the underlying microbiomes's genomes. State-of-the-art tools require big shared memory machines and cannot handle contemporary metagenome datasets that exceed Terabytes in size. In this paper, we introduce the MetaHipMer pipeline, a high-quality and high-performance metagenome assembler that employs an iterative de Bruijn graph approach. MetaHipMer leverages a specialized scaffolding algorithm that produces long scaffolds and accommodates the idiosyncrasies of metagenomes. MetaHipMer is end-to-end parallelized using the Unified Parallel C language and therefore can run seamlessly on shared and distributed-memory systems. Experimental results show that MetaHipMer matches or outperforms the state-of-the-art tools in terms of accuracy. Moreover, MetaHipMer scales efficiently to large concurrencies and is able to assemble previously intractable grand challenge metagenomes. We demonstrate the unprecedented capability of MetaHipMer by computing the first full assembly of the Twitchell Wetlands dataset, consisting of 7.5 billion reads - size 2.6 TBytes.Comment: Accepted to SC1

Substitution Patterns Are Under Different Influences in Primates and Rodents

There are large-scale variations of the GC-content along mammalian chromosomes that have been called isochore structures. Primates and rodents have different isochore structures, which suggests that these lineages exhibit different modes of GC-content evolution. It has been shown that, in the human lineage, GC-biased gene conversion (gBGC), a neutral process associated with meiotic recombination, acts on GC-content evolution by influencing A or T to G or C substitution rates. We computed genome-wide substitution patterns in the mouse lineage from multiple alignments and compared them with substitution patterns in the human lineage. We found that in the mouse lineage, gBGC is active but weaker than in the human lineage and that male-specific recombination better predicts GC-content evolution than female-specific recombination. Furthermore, we were able to show that G or C to A or T substitution rates are predicted by a combination of different factors in both lineages. A or T to G or C substitution rates are most strongly predicted by meiotic recombination in the human lineage but by CpG odds ratio (the observed CpG frequency normalized by the expected CpG frequency) in the mouse lineage, suggesting that substitution patterns are under different influences in primates and rodents

The Impact of Recombination on Nucleotide Substitutions in the Human Genome

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue for detecting selection within sequences. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We analyzed the pattern of neutral substitutions in 1 Gb of primate non-coding regions. We show that the GC-content toward which sequences are evolving is strongly negatively correlated to the distance to telomeres and positively correlated to the rate of crossovers (R2 = 47%). This demonstrates that recombination has a major impact on substitution patterns in human, driving the evolution of GC-content. The evolution of GC-content correlates much more strongly with male than with female crossover rate, which rules out selectionist models for the evolution of isochores. This effect of recombination is most probably a consequence of the neutral process of biased gene conversion (BGC) occurring within recombination hotspots. We show that the predictions of this model fit very well with the observed substitution patterns in the human genome. This model notably explains the positive correlation between substitution rate and recombination rate. Theoretical calculations indicate that variations in population size or density in recombination hotspots can have a very strong impact on the evolution of base composition. Furthermore, recombination hotspots can create strong substitution hotspots. This molecular drive affects both coding and non-coding regions. We therefore conclude that along with mutation, selection and drift, BGC is one of the major factors driving genome evolution. Our results also shed light on variations in the rate of crossover relative to non-crossover events, along chromosomes and according to sex, and also on the conservation of hotspot density between human and chimp

The Sex-Specific Impact of Meiotic Recombination on Nucleotide Composition

Meiotic recombination is an important evolutionary force shaping the nucleotide landscape of genomes. For most vertebrates, the frequency of recombination varies slightly or considerably between the sexes (heterochiasmy). In humans, male, rather than female, recombination rate has been found to be more highly correlated with the guanine and cytosine (GC) content across the genome. In the present study, we review the results in human and extend the examination of the evolutionary impact of heterochiasmy beyond primates to include four additional eutherian mammals (mouse, dog, pig, and sheep), a metatherian mammal (opossum), and a bird (chicken). Specifically, we compared sex-specific recombination rates (RRs) with nucleotide substitution patterns evaluated in transposable elements. Our results, based on a comparative approach, reveal a great diversity in the relationship between heterochiasmy and nucleotide composition. We find that the stronger male impact on this relationship is a conserved feature of human, mouse, dog, and sheep. In contrast, variation in genomic GC content in pig and opossum is more strongly correlated with female, rather than male, RR. Moreover, we show that the sex-differential impact of recombination is mainly driven by the chromosomal localization of recombination events. Independent of sex, the higher the RR in a genomic region and the longer this recombination activity is conserved in time, the stronger the bias in nucleotide substitution pattern, through such mechanisms as biased gene conversion. Over time, this bias will increase the local GC content of the region

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Overview of the Role of Environmental Factors in Neurodevelopmental Disorders

Evidence implicates environmental factors in the pathogenesis of diverse complex neurodevelopmental disorders. However, the identity of specific environmental chemicals that confer risk for these disorders, and the mechanisms by which environmental chemicals interact with genetic susceptibilities to influence adverse neurodevelopmental outcomes remain significant gaps in our understanding of the etiology of most neurodevelopmental disorders. It is likely that many environmental chemicals contribute to the etiology of neurodevelopmental disorders but their influence depends on the genetic substrate of the individual. Research into the pathophysiology and genetics of neurodevelopmental disorders may inform the identification of environmental susceptibility factors that promote adverse outcomes in brain development. Conversely, understanding how low-level chemical exposures influence molecular, cellular, and behavioral outcomes relevant to neurodevelopmental disorders will provide insight regarding gene-environment interactions and possibly yield novel intervention strategies

A Two-Step Theory and Test of Democratic Waves *

Abstract Scholars, observing clustering in transitions to democracy, argue that democratization diffuses across borders as citizens in autocracies demand the same reforms they witness in neighboring states. We disagree. The present paper asserts that the diffusion of democracy literature rests on weak theoretical foundations and does not properly test for diffusion. We advance an alternative two-step argument to explain clustering of democratization: (1) economic shocks, which are clustered spatially and temporally, induce the breakdown of authoritarian regimes; then (2) democratic diffusion, in turn, influences whether a fallen dictatorship will be replaced by a democracy or a new autocracy. Diffusion, despite playing an important role, is insufficient to explain the clustering of transitions, notably because it cannot account for the timing of the waves. Using data on 125 autocracies from 1875 to 2004, we show that economic crises trigger authoritarian breakdowns, while diffusion determines whether the new regime is democratic or authoritarian. * Thanks t