Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI

SUMAC: Constructing Phylogenetic Supermatrices and Assessing Partially Decisive Taxon Coverage

The amount of phylogenetically informative sequence data in GenBank is growing at an exponential rate, and large phylogenetic trees are increasingly used in research. Tools are needed to construct phylogenetic sequence matrices from GenBank data and evaluate the effect of missing data. Supermatrix Constructor (SUMAC) is a tool to data-mine GenBank, construct phylogenetic supermatrices, and assess the phylogenetic decisiveness of a matrix given the pattern of missing sequence data. SUMAC calculates a novel metric, Missing Sequence Decisiveness Scores (MSDS), which measures how much each individual missing sequence contributes to the decisiveness of the matrix. MSDS can be used to compare supermatrices and prioritize the acquisition of new sequence data. SUMAC constructs supermatrices either through an exploratory clustering of all GenBank sequences within a taxonomic group or by using guide sequences to build homologous clusters in a more targeted manner. SUMAC assembles supermatrices for any taxonomic group recognized in GenBank and is optimized to run on multicore computer systems by parallelizing multiple stages of operation. SUMAC is implemented as a Python package that can run as a stand-alone command-line program, or its modules and objects can be incorporated within other programs. SUMAC is released under the open source GPLv3 license and is available at https://github.com/wf8/sumac

Freyman_Onagraceae

This zip file contains all data and scripts used to perform the analyses in Freyman, W.A. and S. Höhna (2018) "Stochastic character mapping of state-dependent diversification reveals the tempo of evolutionary decline in self-compatible lineages

Data from: Stochastic character mapping of state-dependent diversification reveals the tempo of evolutionary decline in self-compatible Onagraceae lineages

A major goal of evolutionary biology is to identify key evolutionary transitions that correspond with shifts in speciation and extinction rates. Stochastic character mapping has become the primary method used to infer the timing, nature, and number of character state transitions along the branches of a phylogeny. The method is widely employed for standard substitution models of character evolution. However, current approaches cannot be used for models that specifically test the association of character state transitions with shifts in diversification rates such as state-dependent speciation and extinction (SSE) models. Here we introduce a new stochastic character mapping algorithm that overcomes these limitations, and apply it to study mating system evolution over a time-calibrated phylogeny of the plant family Onagraceae. Utilizing a hidden state SSE model we tested the association of the loss of self-incompatibility with shifts in diversification rates. Confirming long standing theory, we found that self-compatible lineages have higher extinction rates and lower net diversification rates compared to self-incompatible lineages. Furthermore, these results provide empirical evidence for the "senescing" diversification rates predicted in highly selfing lineages: our mapped character histories show that the loss of self-incompatibility is followed by a short-term spike in speciation rates, which declines after a time lag of several million years resulting in negative net diversification. Lineages that have long been self-compatible such as Fuchsia and Clarkia are in a previously unrecognized and ongoing evolutionary decline. Our results demonstrate that stochastic character mapping of SSE models is a powerful tool for examining the timing and nature of both character state transitions and shifts in diversification rates over the phylogeny

Data from: Cladogenetic and anagenetic models of chromosome number evolution: a Bayesian model averaging approach

Chromosome number is a key feature of the higher-order organization of the genome, and changes in chromosome number play a fundamental role in evolution. Dysploid gains and losses in chromosome number, as well as polyploidization events, may drive reproductive isolation and lineage diversification. The recent development of probabilistic models of chromosome number evolution in the groundbreaking work by Mayrose et al. (2010, ChromEvol) have enabled the inference of ancestral chromosome numbers over molecular phylogenies and generated new interest in studying the role of chromosome changes in evolution. However, the ChromEvol approach assumes all changes occur anagenetically (along branches), and does not model events that are specifically cladogenetic. Cladogenetic changes may be expected if chromosome changes result in reproductive isolation. Here we present a new class of models of chromosome number evolution (called ChromoSSE) that incorporate both anagenetic and cladogenetic change. The ChromoSSE models allow us to determine the mode of chromosome number evolution; is chromosome evolution occurring primarily within lineages, primarily at lineage splitting, or in clade-specific combinations of both? Furthermore, we can estimate the location and timing of possible chromosome speciation events over the phylogeny. We implemented ChromoSSE in a Bayesian statistical framework, specifically in the software RevBayes, to accommodate uncertainty in parameter estimates while leveraging the full power of likelihood based methods. We tested ChromoSSE's accuracy with simulations and re-examined chromosomal evolution in Aristolochia, Carex section Spirostachyae, Helianthus, Mimulus sensu lato (s.l.), and Primula section Aleuritia, finding evidence for clade-specific combinations of anagenetic and cladogenetic dysploid and polyploid modes of chromosome evolution

Data from: Retracing the Hawaiian silversword radiation despite phylogenetic, biogeographic, and paleogeographic uncertainty

The Hawaiian silversword alliance (Asteraceae) is an iconic adaptive radiation. However, like many island plant lineages, no fossils have been assigned to the clade. As a result, the clade's age and diversification rate are not known precisely, making it difficult to test biogeographic hypotheses about the radiation. Without fossils, paleogeographically structured biogeographic processes may inform species divergence times; for example, an island must first exist for a clade to radiate upon it. We date the silversword clade and test biogeographic hypotheses about its radiation across the Hawaiian Archipelago by modeling interactions between species relationships, molecular evolution, biogeographic scenarios, divergence times, and island origination times using the Bayesian phylogenetic framework, RevBayes. The ancestor of living silverswords most likely colonized the modern Hawaiian Islands once from the mainland approximately 5.1 Ma, with the most recent common ancestor of extant silversword lineages first appearing approximately 3.5 Ma. Applying an event-based test of the progression rule of island biogeography, we found strong evidence that the dispersal process prefers old-to-young directionality, but strong evidence for diversification continuing unabated into later phases of island ontogeny, particularly for Kauai. This work serves as a general example for how diversification studies benefit from incorporating biogeographic and paleogeographic components

homologizer: Phylogenetic phasing of gene copies into polyploid subgenomes

Abstract Organisms such as allopolyploids and F1 hybrids contain multiple distinct subgenomes, each potentially with its own evolutionary history. These organisms present a challenge for multilocus phylogenetic inference and other analyses since it is not apparent which gene copies from different loci are from the same subgenome and thus share an evolutionary history. Here we introduce homologizer, a flexible Bayesian approach that uses a phylogenetic framework to infer the phasing of gene copies across loci into their respective subgenomes. Through the use of simulation tests, we demonstrate that homologizer is robust to a wide range of factors, such as incomplete lineage sorting and the phylogenetic informativeness of loci. Furthermore, we establish the utility of homologizer on real data, by analysing a multilocus dataset consisting of nine diploids and 19 tetraploids from the fern family Cystopteridaceae. Finally, we describe how homologizer may potentially be used beyond its core phasing functionality to identify non‐homologous sequences, such as hidden paralogs or contaminants

Inferring the evolutionary reduction of corm lobation in Isoëtes using Bayesian model-averaged ancestral state reconstruction.

PREMISE OF THE STUDY:Inferring the evolution of characters in Isoëtes has been problematic, as these plants are morphologically conservative and yet highly variable and homoplasious within that conserved base morphology. However, molecular phylogenies have given us a valuable tool for testing hypotheses of character evolution within the genus, such as the hypothesis of ongoing morphological reductions. METHODS:We examined the reduction in lobe number on the underground trunk, or corm, by combining the most recent molecular phylogeny with morphological descriptions gathered from the literature and observations of living specimens. Ancestral character states were inferred using nonstationary evolutionary models, reversible-jump MCMC, and Bayesian model averaging. KEY RESULTS:Our results support the hypothesis of a directional reduction in lobe number in Isoëtes, with the best-supported model of character evolution being one of irreversible reduction. Furthermore, the most probable ancestral corm lobe number of extant Isoëtes is three, and a reduction to two lobes has occurred at least six times. CONCLUSIONS:From our results, we can infer that corm lobation, like many other traits in Isoëtes, shows a degree of homoplasy, and yet also shows ongoing evolutionary reduction

Phylogenomics of Perityleae (Compositae) provides new insights into morphological and chromosomal evolution of the rock daisies

Rock daisies (Perityleae; Compositae) are a diverse clade of seven genera and ca. 84 minimum-rank taxa that mostly occur as narrow endemics on sheer rock cliffs throughout the southwest United States and northern Mexico. Taxonomy of Perityleae has traditionally been based on morphology and cytogenetics. To test taxonomic hypotheses and utility of characters emphasized in past treatments, we present the first densely sampled molecular phylogenies of Perityleae and reconstruct trait and chromosome evolution. We inferred phylogenetic trees from whole chloroplast genomes, nuclear ribosomal cistrons, and hundreds of low-copy nuclear genes using genome skimming and target capture. Discordance between sources of molecular data suggests an underappreciated history of hybridization in Perityleae. Phylogenies support the monophyly of subtribe Peritylinae, a distinctive group possessing a four-lobed disc corolla; however, all of the phylogenetic trees generated in this study reject the monophyly of the most species-rich genus, Perityle, as well as its sections: Perityle sect. Perityle, Perityle sect. Laphamia, and Perityle sect. Pappothrix. Using reversible jump MCMC, our results suggest that morphological characters traditionally used to classify members of Perityleae have evolved multiple times within the group. A base chromosome number x = 9 gave rise to higher base numbers in subtribe Peritylinae (x = 12, 13, 16, 17, 18, and 19) through polyploidization, followed by ascending or descending dysploidy. Most taxa constitute a monophyletic lineage with a base chromosome number of x = 17, with multiple neo-polyploidization events. These results demonstrate the advantages and obstacles of next-generation sequencing approaches in synantherology while laying the foundation for taxonomic revision and comparative study of the evolutionary ecology of Perityleae