74 research outputs found

    Hunger Artists: Yeast Adapted to Carbon Limitation Show Trade-Offs under Carbon Sufficiency

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    As organisms adaptively evolve to a new environment, selection results in the improvement of certain traits, bringing about an increase in fitness. Trade-offs may result from this process if function in other traits is reduced in alternative environments either by the adaptive mutations themselves or by the accumulation of neutral mutations elsewhere in the genome. Though the cost of adaptation has long been a fundamental premise in evolutionary biology, the existence of and molecular basis for trade-offs in alternative environments are not well-established. Here, we show that yeast evolved under aerobic glucose limitation show surprisingly few trade-offs when cultured in other carbon-limited environments, under either aerobic or anaerobic conditions. However, while adaptive clones consistently outperform their common ancestor under carbon limiting conditions, in some cases they perform less well than their ancestor in aerobic, carbon-rich environments, indicating that trade-offs can appear when resources are non-limiting. To more deeply understand how adaptation to one condition affects performance in others, we determined steady-state transcript abundance of adaptive clones grown under diverse conditions and performed whole-genome sequencing to identify mutations that distinguish them from one another and from their common ancestor. We identified mutations in genes involved in glucose sensing, signaling, and transport, which, when considered in the context of the expression data, help explain their adaptation to carbon poor environments. However, different sets of mutations in each independently evolved clone indicate that multiple mutational paths lead to the adaptive phenotype. We conclude that yeasts that evolve high fitness under one resource-limiting condition also become more fit under other resource-limiting conditions, but may pay a fitness cost when those same resources are abundant

    Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines

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    The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    A refined chronology for the Gravettian sequence of Abri Pataud

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    Abri Pataud (France) is the type site in studies focusing on the appearance of modern humans and the development of classic Upper Paleolithic technocomplexes in Europe. It contains important evidence of successful adaptation strategies of modern humans to new territories and in response to sharply changing climatic conditions that characterized Marine Isotope Stages 3 and 2. Despite being for decades one of the best excavated and most studied Paleolithic sites, the chronology of Abri Pataud has lacked precision and revealed large discrepancies. The chronology of the lowermost part of the sequence (Levels 14–5) was refined in 2011 with the publication of 32 new radiocarbon determinations, mainly from the Aurignacian levels. In contrast, the Gravettian levels (Levels 5–2) remained poorly dated until now. Here, we present 18 new radiocarbon dates on cut-marked animal bones from the Gravettian part of the site, which complete the dating of this important sequence. The determinations are analyzed using Bayesian statistical modeling, and the results allow us to place the start of the Gravettian at the site between ∼33,000 and 32,000 cal BP (∼29,000–28,000 BP). We discuss the succession of the Gravettian facies across the sequence (Bayacian, Noaillian, Rayssian), as well as the likely duration of each archaeological level. With a total of more than 50 radiocarbon determinations, Abri Pataud offers secure information for the appearance and development of the technocomplexes linked with early modern humans and their establishment in western Europe. Based on published genetic data, it appears that it is the Gravettian hunter-gatherers and subsequent human groups, rather than the earlier Aurignacian and pre-Aurignacian groups, that contributed to the genetic signature of later and living Europeans. Hence, elucidating the precise timing of the Gravettian appearance has broad implications in our understanding of late human evolution across Europe. © 2020 Elsevier Ltd1. Introduction 1.1. Sedimentary context and natural evolution of Abri Pataud 1.2. Gravettian archaeological sequence Level 5: Early Gravettian Level 4: Middle Gravettian (or Noaillian/Rayssian) Level 3: Recent Gravettian Level 2: Final Gravettian 1.3. Previous chronology 2. Materials and methods 2.1. Radiocarbon dating 2.2. Bayesian modeling 3. Results 4. Discussion 4.1. Span and duration of the Gravettian at Abri Pataud 4.2. The Aurignacian to Gravettian transition at Abri Pataud and in western Europe 4.3. Level 5 and the earliest Gravettian of Abri Pataud 4.4. Comparison of Abri Pataud Level 5 with other Early Gravettian sequences 4.5. The Middle Gravettian occupation of Level 4 4.6. Observations on the Recent Gravettian (Level 3) and the Final Gravettian (Level 2) 4.7. The Gravettian genetic legacy 5. Conclusion

    Desert Pavement Disturbance and Artifact Taphonomy: A Case Study from the Eastern Libyan Plateau, Egypt

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    International audienceAccretionary desert pavements on the eastern Libyan Plateau of central Egyptsupport a rich Middle and Upper Paleolithic artifact assemblage exhibiting in-tensive blank production and minimal tool production. These assemblages ap-pear to be in primary context with numerous examples of lithic refits showingon-site lithic production. However, the smallest (length≤2.5 cm) archaeolog-ical fragments are recovered at a much lower rate on this desert pavementsurface than expected given comparable data from lithic assemblages in caveand shelter contexts in France. Excavation of archaeological contexts on theLibyan Plateau reveals the loss of small artifact fragments into the subsur-face due to aeolian accumulation of silts, whereas geomorphic examination ofdesert pavement surfaces suggests a potential for relatively isolated bioturba-tion as a source of lateral and vertical disturbance of desert pavement surfacesover small areas. Archaeologists should be aware of the potential for long-termassemblage stability as well as small artifact burial in surficial desert pavementcontexts.C©2013 Wiley Periodicals, Inc
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