Insights about variation in meiosis from 31,228 human sperm genomes, bioRxiv, 2019-05-02
AbstractMeiosis, while critical for reproduction, is also highly variable and error prone crossover rates vary among humans and individual gametes, and chromosome nondisjunction leads to aneuploidy, a leading cause of miscarriage. To study variation in meiotic outcomes within and across individuals, we developed a way to sequence many individual sperm genomes at once. We used this method to sequence the genomes of 31,228 gametes from 20 sperm donors, identifying 813,122 crossovers, 787 aneuploid chromosomes, and unexpected genomic anomalies. Different sperm donors varied four-fold in the frequency of aneuploid sperm, and aneuploid chromosomes gained in meiosis I had 36% fewer crossovers than corresponding non-aneuploid chromosomes. Diverse recombination phenotypes were surprisingly coordinated donors with high average crossover rates also made a larger fraction of their crossovers in centromere-proximal regions and placed their crossovers closer together. These same relationships were also evident in the variation among individual gametes from the same donor sperm with more crossovers tended to have made crossovers closer together and in centromere-proximal regions. Variation in the physical compaction of chromosomes could help explain this coordination of meiotic variation across chromosomes, gametes, and individuals.
biorxiv genomics 100-200-users 2019Matryoshka RNA virus 1 a novel RNA virus associated with Plasmodium parasites in human malaria, bioRxiv, 2019-05-01
AbstractParasites of the genus Plasmodium cause human malaria. Yet nothing is known about the viruses that infect these divergent eukaryotes. We investigated the Plasmodium virome by performing a meta-transcriptomic analysis of blood samples from malaria patients infected with P. vivax, P. falciparum or P. knowlesi. This revealed a novel bi-segmented narna-like RNA virus restricted to P. vivax and named Matryoshka RNA virus 1 (MaRNAV-1) to reflect its “Russian doll” nature a virus, infecting a parasite, infecting an animal. MaRNAV-1 was abundant in geographically diverse P. vivax from humans and mosquitoes. Notably, a related virus (MaRNAV-2) was identified in Australian birds infected with a Leucocytozoon - eukaryotic parasites that group with Plasmodium in the Apicomplexa subclass hematozoa. This is the first report of a Plasmodium virus. As well as broadening our understanding of the eukaryotic virosphere, the restriction to P. vivax may help understand P. vivax-specific biology in humans and mosquitoes.
biorxiv evolutionary-biology 100-200-users 2019Co-reviewing and ghostwriting by early career researchers in the peer review of manuscripts, bioRxiv, 2019-04-27
AbstractThe goal of this study is to shed light on the involvement of early career researchers (ECRs) during peer review of manuscripts for publication in journals. In particular, we sought to better understand how commonly ECRs contribute ideas andor text to peer review reports when they are not the invited reviewer (“co-review”), and how commonly ECRs do not receive named credit to the journal editorial staff for these scholarly efforts (“ghostwrite”). First, we evaluated 1,952 publications in the peer-reviewed literature generated by exhaustive search terms that combined synonyms of “early career researcher” and “peer review” and found no previous studies about ECRs ghostwriting peer review reports. We then surveyed 498 researchers about their experiences with, and opinions about, co-reviewing and ghostwriting as ECRs. Three quarters of those surveyed have co-reviewed and most find it to be a beneficial (95% agree) and ethical (73% agree) form of training in peer review. Co-reviewing is the second most commonly reported form of training in peer review besides receiving reviews on one’s own papers. Half of survey respondents have ghostwritten a peer review report, despite the 45ths majority opinion that ghostwriting is unethical. Survey respondents report that the three major barriers to including co-reviewer names on peer review reports are a lack of communication between PIs and ECRs; a false belief that co-authorship is for manuscripts but not peer review reports; and prohibitive journal policies that are out of alignment with current practice and opinions about best practice. We therefore propose recommendations for changing this status quo, to discourage unethical ghostwriting of peer review reports and encourage quality co-reviewing experiences as normal training in peer review.
biorxiv scientific-communication-and-education 100-200-users 2019Assembly-free single-molecule nanopore sequencing recovers complete virus genomes from natural microbial communities, bioRxiv, 2019-04-26
AbstractViruses are the most abundant biological entities on Earth, and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule nanopore sequencing approach enabling direct recovery of high-quality viral genome sequences from environmental samples. Our method yielded over a thousand high quality, full-length draft virus genome sequences that could not be fully recovered using short read assembly approaches applied to the same samples. Additionally, novel DNA sequences were discovered whose repeat structures, gene contents and concatemer lengths suggested that they represent phage-inducible chromosomal islands that were packaged as concatemers within phage particles. Our new approach provided novel insight into genome structures, population biology, and ecology of naturally occurring viruses and viral parasites.
biorxiv microbiology 100-200-users 2019Rapid, Low-Cost Detection of Water Contaminants Using Regulated In Vitro Transcription, bioRxiv, 2019-04-26
ABSTRACTSynthetic biology has enabled the development of powerful nucleic acid diagnostic technologies for detecting pathogens and human health biomarkers. Here we expand the reach of synthetic biology-enabled diagnostics by developing a cell-free biosensing platform that uses RNA output sensors activated by ligand induction (ROSALIND) to detect harmful contaminants in aqueous samples. ROSALIND consists of three programmable components highly-processive RNA polymerases, allosteric transcription factors, and synthetic DNA transcription templates. Together, these components allosterically regulate the in vitro transcription of a fluorescence-activating RNA aptamer in the absence of a target compound, transcription is blocked, while in its presence a fluorescent signal is produced. We demonstrate that ROSALIND can be configured to detect a range of water contaminants, including antibiotics, toxic small molecules, and metals. Our cell-free biosensing platform, which can be freeze-dried for field deployment, creates a new capability for point-of-use monitoring of molecular species to address growing global crises in water quality and human health.
biorxiv synthetic-biology 100-200-users 2019