Biology subjects

Senevirathne, G.

Publications and source records attributed to Senevirathne, G..

7 recordsLinked to original sources

bioRxiv2026

Evolutionary trade-offs between growth and reproduction under obesogenic conditions: sex-biased skeletal and gonadal maturation in mice

Adolescence is a brief period during which finite energy resources are reallocated from linear growth toward reproductive maturation. Rising childhood obesity and earlier onset of puberty suggest that modern, energy rich diets may distort these evolved energy allocation rules, but causal mechanisms remain unclear. Here, we expose male and female wild-type and leptin receptor deficient (Db/Db) to either high fat or normal chow diets. We longitudinally analyze metabolic, skeletal, gonadal, endocrine and insulin-receptor phenotypes from 4-10 weeks of age (sexual maturation window in mice). In WT males, HFDs increased adiposity and impaired glucose tolerance, and selectively remodeled joint morphology, advanced gonadal maturation, and shifted insulin receptor expression from growth plates to testes. Together, these changes indicate a rebalancing of energy use toward reproduction at the expense of skeletal and metabolic health. WT females showed subtler systemic metabolic disruption but clear diet-responsive changes in growth plate and ovarian maturation. Our findings indicate that energy-rich diets during adolescence shift evolved allocation rules to prioritize reproductive readiness over skeletal robustness in a sex-dependent manner, with potential consequences for precocious puberty and bone health in humans.

evolutionary biology↗

bioRxiv2024

Leveraging single cell multiomic analyses to identify factors that drive human chondrocyte cell fate

Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. To better understand how human cartilage develops in vivo, we jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femurs at 2 fetal timepoints. We used these multiomic data to identify transcription factors expressed in distinct chondrocyte subtypes, link accessible regulatory elements with gene expression, and predict transcription factor-based regulatory networks that are important for growth plate or epiphyseal chondrocyte differentiation. We developed a human pluripotent stem cell platform for interrogating the function of predicted transcription factors during chondrocyte differentiation and used it to test NFATC2. We expect new regulatory networks we uncovered using multiomic data to be important for promoting cartilage health and treating disease, and our platform to be a useful tool for studying cartilage development in vitro. Statement of SignificanceThe identity and integrity of the articular cartilage lining our joints are crucial to pain-free activities of daily living. Here we identified a gene regulatory landscape of human chondrogenesis at single cell resolution, which is expected to open new avenues of research aimed at mitigating cartilage diseases that affect hundreds of millions of individuals world-wide.

developmental biology↗

bioRxiv2023

A frog adaptive radiation: Ecomorphological evolution in Old-World shrub frogs (Rhacophoridae: Pseudophilautus)

Ecomorphs result from divergent natural selection, leading to species-rich adaptive radiations. Identifying ecomorphs and the resulting adaptive radiations in frogs is challenging due to conserved morphology and high species diversity. In this study, we demonstrate the ecological and climate specializations that have driven the diversification of shrub frogs of the genus Pseudophilautus in Sri Lanka, a tropical continental island. We use a time-calibrated phylogeny, morphometric analyses, and climate-niche evolution, and identify five ecomorphological categories, including Tree-shrub, Rock-boulder, Leaf-litter, Habitat Generalists, and Canopy forms, and describe their evolution. Body size is the primary factor separating species, and specific body features correlate with habitat type. Ecomorphs likely evolved multiple times in disparate lineages, and in different regions and altitudes, during cold climatic periods owing to monsoon cycles resulting from the Himalayan-Tibetan orogeny. The common ancestor was a medium-sized, wet-adapted, tree-shrub habitat specialist which originated in the late Oligocene. Extreme size classes (diminutive leaf litter forms and large canopy forms) evolved recently and suggest that morphological disparity arose late in diversification, possibly aided by favorable climates. This work will facilitate understanding of adaptive radiations in frogs, which possibly will help uncover the prevalence of subtle adaptive radiations in frogs, just as in tailed-vertebrates.

evolutionary biology↗

bioRxiv2021

Molecular Basis of Urostyle Development: Genes and Gene Regulation Underlying an Evolutionary Novelty

Evolutionary novelties entail the origin of morphologies that enable new functions. These features can arise through changes to gene function and regulation. One important novelty is the fused rod at the end of the vertebral column in anurans, the urostyle. This feature is composed of a coccyx and an ossifying hypochord, and both structures ossify during metamorphosis. We used Laser Capture Micro-dissection of these identified tissues and subjected them to RNA-seq and ATAC-seq analyses at three developmental stages in tadpoles of Xenopus tropicalis. These experiments reveal that the coccyx and hypochord have two different molecular signatures. ATAC-seq data reveals potential regulatory regions that are observed in proximity to candidate genes identified from RNA-seq. Neuronal (TUBB3) and muscle markers (MYH3) are upregulated in coccygeal tissues, whereas T-box genes (TBXT, TBXT.2), corticosteroid stress hormones (CRCH.1), and matrix metallopeptidases (MMP1, MMP8, MMP13) are upregulated in the hypochord. Even though an ossifying hypochord is only present in anurans, this ossification between the vertebral column and the notochord appears to resemble a congenital vertebral anomaly seen prenatally in humans, caused by an ectopic expression of the TBXT/TBXT.2 gene. This work opens the way to functional studies that help us better elucidate anuran bauplan evolution.

evolutionary biology↗

bioRxiv2020

Evolution in Sinocyclocheilus cavefish is marked by rate shifts, reversals and origin of novel traits

Epitomized by the well-studied Astyanax mexicanus, cavefishes provide important model organisms to understand adaptations in response to divergent natural selection. However, the spectacular Sinocyclocheilus diversification of China, the most diverse cavefish clade in the world harboring nearly 75 species, demonstrate evolutionary convergence for many traits, yet remain poorly understood in terms of their morphological evolution. Here, using a broad sample of 49 species representative of this diversification, we analyze patterns of Sinocylocheilus evolution in a phylogenetic context. We categorized species into morphs based on eye-related condition: Blind, Micro-eyed (small-eyed), and Normal-eyed and we also considered three habitat types (Troglodytic - cave-restricted; Troglophilic - cave-associated; Surface - outside of caves). Geometric morphometric analyses show Normal-eyed morphs with fusiform shapes being segregated from Blind/Micro-eyed (Eye-regressed) morphs with deeper bodies along the first principal component ("PC") axis. The second PC axis accounts for shape complexity related to the presence of horns. Ancestral character reconstructions of morphs suggest at least three independent origins of Blind morphs, each with different levels of modification in relation to the typical morphology of ancestral Normal-eyed morphs. Interestingly, only some Blind or Micro-eyed morphs bear horns and they are restricted to a single clade (Clade B) and arising from a Troglodytic ancestral species. Our geophylogeny shows an east-to-west diversification spanning the Pliocene and the Pleistocene, with Troglodytic species dominating karstic subterranean habitats of the plains whereas predominantly Surface species inhabit streams and pools in hills to the west (perhaps due to the scarcity of caves). Integration of morphology, phylogeny and geography suggests Sinocyclocheilus are pre-adapted for cave dwelling. Analyses of evolutionary rates suggest that lineages leading to Blind morphs were characterized by significant rate shifts, such as a slowdown in body size evolution and a 3.3 to 12.5 fold increase in the evolutionary rate of eye regression. Furthermore, body size and eye size have undergone reversals, but horns have not, a trait that seem to require substantial evolutionary time to form. These results, compared to the Astyanax model system, indicate Sinocyclocheilus fishes demonstrate extraordinary morphological diversity and variation, offering an invaluable model system to explore evolutionary novelty.

evolutionary biology↗

bioRxiv2020

The West African lungfish provides insights into the evolution of tetrapod tail regeneration

Salamanders, frog tadpoles, and diverse lizards have the remarkable ability to regenerate tails. Paleontological data suggests that this capacity is plesiomorphic, yet when the developmental and genetic architecture of tail regeneration arose is poorly understood. Here we show morphological and molecular hallmarks of tetrapod tail regeneration in the West African lungfish Protopterus annectens, a living representative of the sister group of tetrapods. As in salamanders, lungfish tail regeneration occurs via formation of a proliferative blastema and restores original structures, including muscle, skeleton and spinal cord. In contrast to lizards and similar to salamanders and frogs, lungfish regenerate spinal cord neurons and reconstitute dorsoventral patterning of the tail. Similar to salamander and frog tadpoles, Shh is required for lungfish tail regeneration. Through RNA-seq analysis of uninjured and regenerating tail blastema, we show that the genetic program deployed during lungfish tail regeneration maintains extensive overlap with that of tetrapods, with the upregulation of genes and signaling pathways previously implicated in amphibian and lizard tail regeneration. Furthermore, the lungfish tail blastema showed marked upregulation of genes encoding post-transcriptional RNA processing components and transposon-derived genes. Our results show that developmental processes and genetic program of tetrapod tail regeneration were present at least near the base of the sarcopterygian clade and establish the lungfish as a valuable research system for regenerative biology.

evolutionary biology↗

bioRxiv2019

The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids

Appendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centered on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level. The condition in finned vertebrates is not understood. To address this gap in knowledge, we investigated the development of muscles and nerves in unpaired and paired fins of skates and compared them to those of chain catsharks. During skate and shark embryogenesis, cell populations of muscle precursors and associated spinal nerves at the same axial level contribute to both appendages and body wall, perhaps representing an ancestral condition of gnathostome appendicular neuromuscular systems. Remarkably in skates, this neuromuscular bifurcation as well as colinear Hox expression extend posteriorly to pattern a broad paired fin domain. In addition, we identified migratory muscle precursors (MMPs), which are known to develop into paired appendage muscles with Pax3 and Lbx1 gene expression, in the dorsal fins of skates. Our results suggest that muscles of paired fins have evolved via redeployment of the genetic program of MMPs that were already involved in dorsal fin development. Appendicular neuromuscular systems most likely have emerged as side branches of body wall neuromusculature and have been modified to adapt to distinct aquatic and terrestrial habitats.

evolutionary biology↗