Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings, bioRxiv, 2019-05-13
AbstractRecent super-resolution microscopy studies have unveiled a periodic scaffold of actin rings regularly spaced by spectrins under the plasma membrane of axons. However, ultrastructural details are unknown, limiting a molecular and mechanistic understanding of these enigmatic structures. Here, we combine platinum-replica electron and optical super-resolution micros-copy to investigate the cortical cytoskeleton of axons at the ultrastructural level. We resolve actin rings as braids made of two long, intertwined actin filaments connected by a dense mesh of aligned spectrins. This molecular arrangement contrasts with the currently assumed model of actin rings made of short, capped actin filaments. We propose that braided rings explain the stability of the actin-spectrin scaffold and ultimately help preserving the axon integrity.
biorxiv cell-biology 200-500-users 2019A comparison of eDNA to camera trapping for assessment of terrestrial mammal diversity, bioRxiv, 2019-05-11
AbstractEnvironmental DNA (eDNA) is one of the most promising approaches to meet the demand for the fast and frequent monitoring of ecosystems needed to tackle the current decline in biodiversity. However, before eDNA can establish itself as a robust alternative for mammal monitoring, comparison with existing approaches is necessary, yet has not been done. Moreover, much is unknown regarding the nature, spread and persistence of DNA shed by animals into terrestrial environments, or the optimal experimental design for understanding these potential biases.To address some of these challenges, we compared the detection of terrestrial mammals using eDNA analysis of soil samples against confirmed species observations from a long-term (∼9-yr) camera trapping study. At the same time, we considered multiple experimental parameters, including two sampling designs, two DNA extraction kits and two metabarcodes of different sizes.All mammals consistently recorded with cameras were detected in eDNA. In addition, eDNA reported many small mammals not recorded by camera traps, but whose presence in the study area is otherwise documented. A long metabarcode (≈220bp) offering a high taxonomic resolution, achieved a similar efficiency as a shorter one (≈70bp) and a phosphate buffer-based extraction gave similar results as a total DNA extraction method for a fraction of the price. Our results support that eDNA-based monitoring should become a valuable part of terrestrial mammal surveys. Yet, the lack of coverage of mammal mitochondrial genomes in public databases must be addressed before eDNA can be used to its full potential.
biorxiv ecology 200-500-users 2019Dsuite - fast D-statistics and related admixture evidence from VCF files, bioRxiv, 2019-05-11
AbstractSummaryThe D-statistic, also known as the ABBA-BABA statistic, and related statistics are commonly used to assess evidence of gene flow between populations or closely related species. While the calculations are not computationally intensive, currently available implementations require custom file formats and are impractical to evaluate all gene flow hypotheses across datasets that include many populations or species. Dsuite is a fast C++ implementation, allowing genome scale calculations of the D-statistic across all combinations of tens or even hundreds of populations or species directly from a variant call format (VCF) file. Furthermore, the program can estimate the admixture fraction and provide evidence of whether introgression is confined to specific loci. Thus Dsuite facilitates assessment of gene flow across large genomic datasets.Availability and implementationSource code and documentation are available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsgithub.commillanekDsuite>httpsgithub.commillanekDsuite<jatsext-link>
biorxiv genomics 0-100-users 2019Fine-scale haplotype structure reveals strong signatures of positive selection in a recombining bacterial pathogen, bioRxiv, 2019-05-11
ABSTRACTIdentifying the forces that create and shape ecologically meaningful variation in bacteria remains an important challenge. For recombining bacteria, the sign and strength of linkage provide a unique lens into ongoing selection. We show derived alleles less than 300bp apart in Neisseria gonorrhoeae exhibit more coupling linkage than repulsion linkage, a pattern that cannot be explained by limited recombination or neutrality as these couplings are significantly stronger for nonsynonymous alleles compared to synonymous alleles. While linkage is shaped by many evolutionary processes, extensive simulations show only two distinct forms of positive selection can drive an excess of coupling linkage between neighboring nonsynonymous alleles directional selection on introgressed alleles or selection that maintains distinct haplotypes in the presence of recombination. Our results establish a framework for identifying patterns of selection in fine-scale haplotype structure that indicate specific ecological processes in species that recombine with distantly related lineages or possess coexisting adaptive haplotypes.
biorxiv evolutionary-biology 0-100-users 2019Improved assembly and variant detection of a haploid human genome using single-molecule, high-fidelity long reads, bioRxiv, 2019-05-11
AbstractThe sequence and assembly of human genomes using long-read sequencing technologies has revolutionized our understanding of structural variation and genome organization. We compared the accuracy, continuity, and gene annotation of genome assemblies generated from either high-fidelity (HiFi) or continuous long-read (CLR) datasets from the same complete hydatidiform mole human genome. We find that the HiFi sequence data assemble an additional 10% of duplicated regions and more accurately represent the structure of tandem repeats, as validated with orthogonal analyses. As a result, an additional 5 Mbp of pericentromeric sequences are recovered in the HiFi assembly, resulting in a 2.5-fold increase in the NG50 within 1 Mbp of the centromere (HiFi 480.6 kbp, CLR 191.5 kbp). Additionally, the HiFi genome assembly was generated in significantly less time with fewer computational resources than the CLR assembly. Although the HiFi assembly has significantly improved continuity and accuracy in many complex regions of the genome, it still falls short of the assembly of centromeric DNA and the largest regions of segmental duplication using existing assemblers. Despite these shortcomings, our results suggest that HiFi may be the most effective stand-alone technology for de novo assembly of human genomes.
biorxiv genomics 0-100-users 2019Jumping To Conclusions, General Intelligence, And Psychosis Liability Findings From The Multi-Centre EU-GEI Case-Control Study, bioRxiv, 2019-05-11
AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of casecontrol differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI −0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= −1.7, 95% CI −2.8 to −0.5, p=0.006), but did not relate to delusions in patients.Conclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.
biorxiv neuroscience 0-100-users 2019