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In rapidly adapting asexual populations, including many microbial pathogens and viruses, numerous mutant lineages often compete for dominance within the population.sup.1-5. These complex evolutionary dynamics determine the outcomes of adaptation, but have been difficult to observe directly. Previous studies have used whole-genome sequencing to follow molecular adaptation.sup.6-10; however, these methods have limited resolution in microbial populations. Here we introduce a renewable barcoding system to observe evolutionary dynamics at high resolution in laboratory budding yeast. We find nested patterns of interference and hitchhiking even at low frequencies. These events are driven by the continuous appearance of new mutations that modify the fates of existing lineages before they reach substantial frequencies. We observe how the distribution of fitness within the population changes over time, and find a travelling wave of adaptation that has been predicted by theory.sup.11-17. We show that clonal competition creates a dynamical 'rich-get-richer' effect: fitness advantages that are acquired early in evolution drive clonal expansions, which increase the chances of acquiring future mutations. However, less-fit lineages also routinely leapfrog over strains of higher fitness. Our results demonstrate that this combination of factors, which is not accounted for in existing models of evolutionary dynamics, is critical in determining the rate, predictability and molecular basis of adaptation. A renewable barcoding system reveals the evolutionary dynamics of laboratory budding yeast, showing that fitness changes over time in a travelling wave of adaptation that can fluctuate owing to leapfrogging events., Author(s): Alex N. Nguyen Ba [sup.1] , Ivana Cvijovic [sup.1] [sup.2] [sup.3] [sup.4] , José I. Rojas Echenique [sup.1] , Katherine R. Lawrence [sup.1] [sup.5] , Artur Rego-Costa [sup.1] , [...]

Defining the transcriptomic identity of malignant cells is challenging in the absence of surface markers that distinguish cancer clones from one another, or from admixed non-neoplastic cells. To address this challenge, here we developed Genotyping of Transcriptomes (GoT), a method to integrate genotyping with high-throughput droplet-based single-cell RNA sequencing. We apply GoT to profile 38,290 CD34.sup.+ cells from patients with CALR-mutated myeloproliferative neoplasms to study how somatic mutations corrupt the complex process of human haematopoiesis. High-resolution mapping of malignant versus normal haematopoietic progenitors revealed an increasing fitness advantage with myeloid differentiation of cells with mutated CALR. We identified the unfolded protein response as a predominant outcome of CALR mutations, with a considerable dependency on cell identity, as well as upregulation of the NF-[kappa]B pathway specifically in uncommitted stem cells. We further extended the GoT toolkit to genotype multiple targets and loci that are distant from transcript ends. Together, these findings reveal that the transcriptional output of somatic mutations in myeloproliferative neoplasms is dependent on the native cell identity. Profiling of over 38,000 CD34.sup.+ cells from patients with CALR-mutated myeloproliferative neoplasms, using the 'Genotyping of Transcriptomes' procedure, reveals that the transcriptional output of these mutations depends upon native cell identity., Author(s): Anna S. Nam [sup.1] [sup.2] [sup.3] , Kyu-Tae Kim [sup.2] [sup.3] [sup.4] , Ronan Chaligne [sup.2] [sup.3] [sup.4] , Franco Izzo [sup.2] [sup.3] [sup.4] , Chelston Ang [sup.2] [sup.3] [...]

A method for detecting mutations and measuring gene-expression levels in the same cell has enabled an investigation into the effects of mutations in a specific gene on the emergence of a form of blood cancer. A combined method probes DNA and RNA in blood progenitor cells., Author(s): Siddharth Raju, Chun Jimmie Ye Author Affiliations: How mutations express themselves in blood-cell production The cells that circulate in the bloodstream perform various functions and, in adults, are derived [...]