Biology subjects

Parsons, T.

Publications and source records attributed to Parsons, T..

8 recordsLinked to original sources

bioRxiv2026

Geomorphic evolution of a Caribbean biological hotspot

Continental shelf archipelagos offer rare opportunities to test island biogeography in a time-resolved, non-equilibrium setting because postglacial sea-level rise drives datable changes in both island area and isolation. Yet most near-shore systems still lack reconstructions that integrate spatial changes in island configuration with duration-weighted histories of fragmentation. Such information is essential for interpreting modern genomic and biodiversity patterns and for evaluating responses to fragmentation such as extinction debt, immigration lag and adaptive responses over time. Here we reconstruct the land-sea geomorphic history of the Bocas del Toro Archipelago, Panama, combining high-resolution bathymetry and topography with a sea-level model corrected for sedimentation and tectonic movement. From this, we quantify multi-scale isolation, historical fragmentation dynamics, and composite metrics that integrate space and time. We show that present-day islands became isolated sequentially from 9.5 to 2.9 ka, with post-isolation area contraction rates varying 20-fold among islands. Over the same interval, shallow marine habitat (0-10 m depth) expanded ninefold as shelf flooding created space for reefs, seagrass, and mangroves. Extending the analyses through the Pleistocene reveals the modern archipelago is atypical and for much of the last million years, the region existed as continuous coastal lowland rather than discrete islands. Projections under moderate emissions scenarios predict [~]5% terrestrial habitat loss but [~]50% expansion of shallow marine habitat by 2150, though whether degraded Caribbean reefs can exploit this expansion remains uncertain. Exploratory correlations between species richness of terrestrial vertebrate groups and geomorphometric predictors reveal that island area, maximum elevation, and cumulative habitat availability since isolation are the strongest correlates of diversity, whilst buffer-zone isolation indices are confounded by covariation between island size and surrounding landmass in this continental shelf context. Overall, Bocas del Toro provides a time-calibrated natural experiment for testing how dynamic connectivity and isolation shaped island and coastal biodiversity.

evolutionary biology↗

bioRxiv2025

JARID2 Inhibition Reprograms Human Hematopoietic Progenitor Cells To Enhance Bone Marrow Transplantation

Hematopoietic stem cell transplantation is a common treatment for many blood disorders and can be a life-saving therapy for patients with leukemias, lymphomas and multiple myeloma. Umbilical cord blood (UCB) serves as a valuable source of hematopoietic stem and progenitor cells (HSPCs) for transplantation, particularly for patients lacking a matched donor. However, the limited number of repopulating cells in UCB units restricts its clinical utility. Our prior studies showed that genetic deletion of the polycomb repressive complex 2 (PRC2) co-factor Jarid2 in mouse multipotent progenitors (MPPs) conveyed ectopic self-renewal capacity. Here, we hypothesized that the function of human HSPCs could be enhanced through JARID2 inhibition. In this study, we demonstrate that both constitutive and transient knockdown of JARID2 increases the number and enhances the functionality of human HSPCs both in vitro and in vivo. This phenotype was distinct from inhibition of EZH2 in UCB cells, suggesting the mechanism was independent of PRC2 co-factor activity of JARID2. Mechanistically, JARID2 knockdown promotes a quiescent, long-term self-renewal gene expression program governed by upregulating STAT1 and characterized by an MHC class II immunophenotype. Analogous to mice, these mechanisms conferred HSC-like potential to human MPPs in vivo. Taken together, these findings highlight JARID2 inhibition as a novel and reversible approach to expand functional UCB-derived HSPCs ex vivo, potentially improving access to stem cell transplantation for a wider patient population. One Sentence SummaryGenetic inhibition of JARID2 enhances repopulating activity of human hematopoietic stem and progenitor cells in vivo via STAT1 upregulation.

developmental biology↗

bioRxiv2024

Relaxed selection can speed the evolution of complex adaptations

Natural selection drives adaptive evolution and removes deleterious mutations; these effects are countervailing when a complex adaptation requires mutations that are initially deleterious when they arise, but beneficial in combination. While many models of this dynamic consider how genetic drift or other influences can aid valley crossing by weakening selection, we lack a general, analytical treatment of when relaxed selection might speed this type of adaptation. Here we use simulation and analysis to show that relaxed selection is generally favorable for valley-crossing when adaptive pathways require more than a single deleterious step. We also demonstrate that spatial heterogeneity in selection pressures could, by relaxing selection, allow populations to cross valleys much more rapidly than expected. These results relate to several applications of evolutionary theory to complex systems ranging from host-pathogen evolution to search algorithms in computer science.

evolutionary biology↗

bioRxiv2023

Large effects and the infinitesimal model

The infinitesimal model of quantitative genetics relies on the Central Limit Theorem to stipulate that under additive models of quantitative traits determined by many loci having similar effect size, the difference between an offsprings genetic trait component and the average of their two parents genetic trait components is Normally distributed and independent of the parents values. Here, we investigate how the assumption of similar effect sizes affects the model: in particular, if the tail of the effect size distribution is polynomial with exponent < 2, then sums of effects should be well-approximated by a "stable distribution", and find tail exponents between 1 and 2 in effect sizes estimated by genome-wide association studies of many human disease-related traits. We show that the independence of offspring trait deviations from parental averages in many cases implies a Gaussian distribution, suggesting that non-Gaussian models of trait evolution must explicitly track the underlying genetics, at least for loci of large effect. We also characterize possible limiting trait distributions of the infinitesimal model with infinitely divisible noise distributions, and compare our results to simulations.

evolutionary biology↗

bioRxiv2020

Microbial community modelling and diversity estimation using the hierarchical Pitman-Yor process

BackgroundThe human microbiome comprises the microorganisms that inhabit the various locales of the human body and plays a vital role in human health. The composition of a microbial population is often quantified through measures of species diversity, which summarize the number of species along with their relative abundances into a single value. In a microbiome sample there will certainly be species missing from the target population which will affect the diversity estimates. MethodsWe employ a model based on the hierarchical Pitman-Yor (HPY) process to model the species abundance distributions over multiple populations. The model parameters are estimated using a Gibbs sampler. We also derive estimates of species diversity, conditional and unconditional on the observed data, as a function of the HPY parameters Finally, we derive a general formula for the Hill numbers in the HPY context. ResultsWe show that the Gibbs sampler for the HPY model performs well in simulations. We also show that the conditional estimates of diversity from the HPY model improve over naive estimates when species are missing. Similarly the conditional HPY estimates tend to perform better than the naive estimates especially when the number of individuals sampled from a population is small.

bioinformatics↗

bioRxiv2019

Estimating Diversity Through Time using Molecular Phylogenies: Old and Species-Poor Frog Families are the Remnants of a Diverse Past

Estimating how the number of species in a given group varied in the deep past is of key interest to evolutionary biologists. However, current phylogenetic approaches for obtaining such estimates have limitations, such as providing unrealistic diversity estimates at the origin of the group. Here we develop a robust probabilistic approach for estimating Diversity-Through-Time (DTT) curves and uncertainty around these estimates from phylogenetic data. We show with simulations that under various realistic scenarios of diversification, this approach performs better than previously proposed approaches. We also characterize the effect of tree size and undersampling on the performance of the approach. We apply our method to understand patterns of species diversity in anurans (frogs and toads). We find that Archaeobatrachia - a species-poor group of old frog clades often found in temperate regions - formerly had much higher diversity and net diversification rate, but the group declined in diversity as younger, nested clades diversified. This diversity decline seems to be linked to a decline in speciation rate rather than an increase in extinction rate. Our approach, implemented in the R package RPANDA, should be useful for evolutionary biologists interested in understanding how past diversity dynamics have shaped present-day diversity. It could also be useful in other contexts, such as for analyzing clade-clade competitive effects or the effect of species richness on phenotypic divergence. [phylogenetic comparative methods; birth-death models; diversity curves; diversification; extinction; anurans]

evolutionary biology↗

bioRxiv2018

Critical Role of Histone Tail Entropy in Nucleosome Unwinding

The nucleosome is the fundamental packaging unit for the genome. It must both remain tightly wound to ensure genome stability while simultaneously being flexible enough to keep the DNA molecule accessible for genome function. The set of physicochemical interactions responsible for the delicate balance between these naturally opposed processes have not been determined due to challenges in resolving partially unwound nucleosome configurations at atomic resolution. Using a near atomistic protein-DNA model and advanced sampling techniques, we calculate the free energy cost of nucleosome DNA unwinding. Our simulations identify a large energetic barrier that decouples the outer and inner DNA unwinding into two separate processes, occurring on different timescales. This dynamical decoupling allows the exposure of outer DNA at a modest cost to ensure accessibility while keeping the inner DNA and the histone core intact to maintain stability. We also reveal that this energetic barrier arises from a delayed loss of contacts between disordered histone tails and the DNA, and is, surprisingly, largely offset by an entropic contribution from these tails. Our study uncovers the balance of energetic and entropic contributions that dictate nucleosome stability, suggesting that tilting this balance may be a previously-unknown mechanism for regulating genome function.

biophysics↗

bioRxiv2017

Pathogen evolution: slow and steady spreads the best

The theory of life history evolution provides a powerful framework to understand the evolutionary dynamics of pathogens in both epidemic and endemic situations. This framework, however, relies on the assumption that pathogen populations are very large and that one can neglect the effects of demographic stochasticity. Here we expand the theory of life history evolution to account for the effects of finite population size on the evolution of pathogen virulence. We show that demographic stochasticity introduces additional evolutionary forces that can qualitatively affect the dynamics and the evolutionary outcome. We discuss the importance of the shape of pathogen fitness landscape and host heterogeneity on the balance between mutation, selection and genetic drift. In particular, we discuss scenarios where finite population size can dramatically affect classical predictions of deterministic models. This analysis reconciles Adaptive Dynamics with population genetics in finite populations and thus provides a new theoretical toolbox to study life-history evolution in realistic ecological scenarios.

evolutionary biology↗