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Manivannan, M.

Publications and source records attributed to Manivannan, M..

3 recordsLinked to original sources

A passage through India: the biotic ferry model supports the build-up of Indo-Australian biodiversity of an ancient soil arthropod clade

AimScutigeromorpha is a globally distributed, ancient group of centipedes with at least 400 million years of evolutionary history. We assess the biogeographic history of the order, with a particular focus on the Peninsular Indian Plate (PIP), a Gondwanan fragment. We hypothesize that continental vicariance explains the disjunct distribution of extant scutigeromorphs, that PIP scutigeromorphs are of ancient Gondwanan origins, and that East Gondwana vicariance explains the diversification of the subfamily Thereuoneminae into its Asian and Australian clades. LocationGlobal TaxaCentipedes, Scutigeromorpha MethodsWe use a novel molecular dataset sampled across the PIP and a global sequence database representing the geographic distribution of all families and subfamilies. We employ molecular phylogenetic analyses on two mitochondrial and three nuclear markers, molecular species delimitation and ancestral range estimation to reconstruct biogeographic history. ResultsAncestral scutigeromorphs were likely widely distributed across Gondwana and diverged prior to any continental vicariance. Scutigeromorph biogeography is shaped by continental vicariance, long-distance dispersal and jump dispersal, indicating an ability to colonize areas far from their ancestral range. The PIP emerged as the ancestral range of Thereuoneminae, which started diversifying during the Cretaceous Period. Subsequent in-situ diversification within the PIP and dispersals into Asia, Australia, and the Pacific Islands best explained the extant distribution of Thereuoneminae, more so than East Gondwana vicariance. Main conclusionsThe in-situ diversification of PIP species and their ancient divergence suggest they represent Gondwanan relicts in a landmass whose biota is primarily dispersal-driven. A single dispersal event from the PIP generated most of the extant diversity in Australia, another Gondwanan fragment. Furthermore, the discovery of 11 putative species from the PIP and the Andaman Islands, five times more than was known, highlights the Wallacean and Linnean shortfalls in tropical Asia.

evolutionary biology↗

Single cell mutational profiling delineates clonal trajectories in myeloid malignancies

Myeloid malignancies, including acute myeloid leukemia (AML), arise from the proliferation and expansion of hematopoietic stem and progenitor cells which acquire somatic mutations. Bulk molecular profiling studies on patient samples have suggested that somatic mutations are obtained in a step-wise fashion, where mutant genes with high variant allele frequencies (VAFs) are proposed to occur early in disease development and mutations with lower VAFs are thought to be acquired later in disease progression1-3. Although bulk sequencing informs leukemia biology and prognostication, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity and clone size, or offer definitive evidence of mutational order. To elucidate the clonal framework of myeloid malignancies, we performed single cell mutational profiling on 146 samples from 123 patients. We found AML is most commonly comprised of a small number of dominant clones, which in many cases harbor co-occurring mutations in epigenetic regulators. Conversely, mutations in signaling genes often occur more than once in distinct subclones consistent with increasing clonal diversity. We also used these data to map the clonal trajectory of each patient and found that specific mutation combinations (FLT3-ITD + NPM1c) synergize to promote clonal expansion and dominance. We combined cell surface protein expression with single cell mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our studies of clonal architecture at a single cell level provide novel insights into the pathogenesis of myeloid transformation and how clonal complexity contributes to disease progression.

cancer biology↗

High throughput expression profiling and in situ screening of circular RNAs in tissues

Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for high-throughput screening of circRNAs and their linear counterparts. We also applied padlock probes and in situ sequencing to visualize and determine circRNAs localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results demonstrate the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.

genomics↗