Although reconstruction of the phylogeny of living birds has progressed tremendously in the last decade, the evolutionary history of Neoaves--a clade that encompasses nearly all living bird ...species--remains the greatest unresolved challenge in dinosaur systematics. Here we investigate avian phylogeny with an unprecedented scale of data: >390,000 bases of genomic sequence data from each of 198 species of living birds, representing all major avian lineages, and two crocodilian outgroups. Sequence data were collected using anchored hybrid enrichment, yielding 259 nuclear loci with an average length of 1,523 bases for a total data set of over 7.8 × 10(7) bases. Bayesian and maximum likelihood analyses yielded highly supported and nearly identical phylogenetic trees for all major avian lineages. Five major clades form successive sister groups to the rest of Neoaves: (1) a clade including nightjars, other caprimulgiforms, swifts, and hummingbirds; (2) a clade uniting cuckoos, bustards, and turacos with pigeons, mesites, and sandgrouse; (3) cranes and their relatives; (4) a comprehensive waterbird clade, including all diving, wading, and shorebirds; and (5) a comprehensive landbird clade with the enigmatic hoatzin (Opisthocomus hoazin) as the sister group to the rest. Neither of the two main, recently proposed Neoavian clades--Columbea and Passerea--were supported as monophyletic. The results of our divergence time analyses are congruent with the palaeontological record, supporting a major radiation of crown birds in the wake of the Cretaceous-Palaeogene (K-Pg) mass extinction.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The rapid increase in number of sequenced genomes for species across of the tree of life is revealing a diverse suite of orthologous genes that could potentially be employed to inform molecular ...phylogenetic studies that encompass broader taxonomic sampling. Optimal usage of this diversity of loci requires user-friendly tools to facilitate widespread cost-effective locus prioritization for phylogenetic sampling. The Townsend (2007) phylogenetic informativeness provides a unique empirical metric for guiding marker selection. However, no software or automated methodology to evaluate sequence alignments and estimate the phylogenetic informativeness metric has been available.
Here, we present PhyDesign, a platform-independent online application that implements the Townsend (2007) phylogenetic informativeness analysis, providing a quantitative prediction of the utility of loci to solve specific phylogenetic questions. An easy-to-use interface facilitates uploading of alignments and ultrametric trees to calculate and depict profiles of informativeness over specified time ranges, and provides rankings of locus prioritization for epochs of interest.
By providing these profiles, PhyDesign facilitates locus prioritization increasing the efficiency of sequencing for phylogenetic purposes compared to traditional studies with more laborious and low capacity screening methods, as well as increasing the accuracy of phylogenetic studies. Together with a manual and sample files, the application is freely accessible at http://phydesign.townsend.yale.edu.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the rise of genome-scale data sets, there has been a call for increased data scrutiny and careful selection of loci that are appropriate to use in an attempt to resolve a phylogenetic problem. ...Such loci should maximize phylogenetic information content while minimizing the risk of homoplasy. Theory posits the existence of characters that evolve at an optimum rate, and efforts to determine optimal rates of inference have been a cornerstone of phylogenetic experimental design for over two decades. However, both theoretical and empirical investigations of optimal rates have varied dramatically in their conclusions: spanning no relationship to a tight relationship between the rate of change and phylogenetic utility. Herein, we synthesize these apparently contradictory views, demonstrating both empirical and theoretical conditions under which each is correct. We find that optimal rates of characters—not genes—are generally robust to most experimental design decisions. Moreover, consideration of site rate heterogeneity within a given locus is critical to accurate predictions of utility. Factors such as taxon sampling or the targeted number of characters providing support for a topology are additionally critical to the predictions of phylogenetic utility based on the rate of character change. Further, optimality of rates and predictions of phylogenetic utility are not equivalent, demonstrating the need for further development of comprehensive theory of phylogenetic experimental design.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Changes in gene expression have been hypothesized to play an important role in the evolution of divergent morphologies. To test this hypothesis in a model system, we examined differences in fruiting ...body morphology of five filamentous fungi in the Sordariomycetes, culturing them in a common garden environment and profiling genome-wide gene expression at five developmental stages. We reconstructed ancestral gene expression phenotypes, identifying genes with the largest evolved increases in gene expression across development. Conducting knockouts and performing phenotypic analysis in two divergent species typically demonstrated altered fruiting body development in the species that had evolved increased expression. Our evolutionary approach to finding relevant genes proved far more efficient than other gene deletion studies targeting whole genomes or gene families. Combining gene expression measurements with knockout phenotypes facilitated the refinement of Bayesian networks of the genes underlying fruiting body development, regulation of which is one of the least understood processes of multicellular development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For COVID-19, it is vital to understand if quarantines shorter than 14 days can be equally effective with judiciously deployed testing. Here, we develop a mathematical model that quantifies the ...probability of post-quarantine transmission incorporating testing into travel quarantine, quarantine of traced contacts with an unknown time of infection, and quarantine of cases with a known time of exposure. We find that testing on exit (or entry and exit) can reduce the duration of a 14-day quarantine by 50%, while testing on entry shortens quarantine by at most one day. In a real-world test of our theory applied to offshore oil rig employees, 47 positives were obtained with testing on entry and exit to quarantine, of which 16 had tested negative at entry; preventing an expected nine offshore transmission events that each could have led to outbreaks. We show that appropriately timed testing can make shorter quarantines effective.
The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, ...we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.
The genomic analyses of pediatric acute lymphoblastic leukemia (ALL) subtypes, particularly T-cell and B-cell lineages, have been pivotal in identifying potential therapeutic targets. Typical genomic ...analyses have directed attention toward the most commonly mutated genes. However, assessing the contribution of mutations to cancer phenotypes is crucial. Therefore, we estimated the cancer effects (scaled selection coefficients) for somatic substitutions in T-cell and B-cell cohorts, revealing key insights into mutation contributions. Cancer effects for well-known, frequently mutated genes like NRAS and KRAS in B-ALL were high, which underscores their importance as therapeutic targets. However, less frequently mutated genes IL7R, XBP1, and TOX also demonstrated high cancer effects, suggesting pivotal roles in the development of leukemia when present. In T-ALL, KRAS and NRAS are less frequently mutated than in B-ALL. However, their cancer effects when present are high in both subtypes. Mutations in PIK3R1 and RPL10 were not at high prevalence, yet exhibited some of the highest cancer effects in individual T-cell ALL patients. Even CDKN2A, with a low prevalence and relatively modest cancer effect, is potentially highly relevant for the epistatic effects that its mutated form exerts on other mutations. Prioritizing investigation into these moderately frequent but potentially high-impact targets not only presents novel personalized therapeutic opportunities but also enhances the understanding of disease mechanisms and advances precision therapeutics for pediatric ALL.
The resolution of four controversial topics in phylogenetic experimental design hinges upon the informativeness of characters about the historical relationships among taxa. These controversies regard ...the power of different classes of phylogenetic character, the relative utility of increased taxonomic versus character sampling, the differentiation between lack of phylogenetic signal and a historical rapid radiation, and the design of taxonomically broad phylogenetic studies optimized by taxonomically sparse genome-scale data. Quantification of the informativeness of characters for resolution of phylogenetic hypotheses during specified historical epochs is key to the resolution of these controversies. Here, such a measure of phylogenetic informativeness is formulated. The optimal rate of evolution of a character to resolve a dated four-taxon polytomy is derived. By scaling the asymptotic informativeness of a character evolving at a nonoptimal rate by the derived asymptotic optimum, and by normalizing so that net phylogenetic informativeness is equivalent for all rates when integrated across all of history, an informativeness profile across history is derived. Calculation of the informativeness per base pair allows estimation of the cost-effectiveness of character sampling. Calculation of the informativeness per million years allows comparison across historical radiations of the utility of a gene for the inference of rapid adaptive radiation. The theory is applied to profile the phylogenetic informativeness of the genes BRCA1, RAG1, GHR, and c-myc from a muroid rodent sequence data set. Bounded integrations of the phylogenetic profile of these genes over four epochs comprising the diversifications of the muroid rodents, the mammals, the lobe-limbed vertebrates, and the early metazoans demonstrate the differential power of these genes to resolve the branching order among ancestral lineages. This measure of phylogenetic informativeness yields a new kind of information for evaluation of phylogenetic experiments. It conveys the utility of the addition of characters a phylogenetic study and it provides a basis for deciding whether appropriate phylogenetic power has been applied to a polytomy that is proposed to be a rapid radiation. Moreover, it provides a quantitative measure of the capacity of a gene to resolve soft polytomies.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Mutational processes in tumors create distinctive patterns of mutations, composed of neutral “passenger” mutations and oncogenic drivers that have quantifiable effects on the proliferation ...and survival of cancer cell lineages. Increases in proliferation and survival are mediated by natural selection, which can be quantified by comparing the frequency at which we detect substitutions to the frequency at which we expect to detect substitutions assuming neutrality. Most of the variants detectable with whole-exome sequencing in tumors are neutral or nearly neutral in effect, and thus the processes generating the majority of mutations may not be the primary sources of the tumorigenic mutations. Across 24 cancer types, we identify the contributions of mutational processes to each oncogenic variant and quantify the degree to which each process contributes to tumorigenesis. We demonstrate that the origination of variants driving melanomas and lung cancers is predominantly attributable to the preventable, exogenous mutational processes associated with ultraviolet light and tobacco exposure, respectively, whereas the origination of selected variants in gliomas and prostate adenocarcinomas is largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and apolipoprotein B mRNA-editing enzyme activity account for a large proportion of the cancer effect within head-and-neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches—revealing the burden of cancer driven by single-nucleotide variants caused by either endogenous or exogenous, nonpreventable, or preventable processes, and crucially inform public health strategies.
Strategies for containing Ebola in West Africa Pandey, Abhishek; Atkins, Katherine E.; Medlock, Jan ...
Science (American Association for the Advancement of Science),
11/2014, Letnik:
346, Številka:
6212
Journal Article
Recenzirano
Odprti dostop
The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. To assess the effectiveness of containment strategies, we developed a stochastic model of Ebola ...transmission between and within the general community, hospitals, and funerals, calibrated to incidence data from Liberia. We find that a combined approach of case isolation, contact-tracing with quarantine, and sanitary funeral practices must be implemented with utmost urgency in order to reverse the growth of the outbreak. As of 19 September, under status quo, our model predicts that the epidemic will continue to spread, generating a predicted 224 (134 to 358) daily cases by 1 December, 280 (184 to 441) by 15 December, and 348 (249 to 545) by 30 December.
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