Biology subjects

Edsinger, E.

Publications and source records attributed to Edsinger, E..

8 recordsLinked to original sources

bioRxiv2024

Genomic Hotspots: Localized chromosome gene expansions identify lineage-specific innovations as targets for functional biodiversity and predictions of stress resilience.

1Functional and biodiversity genomics is essential for assessment and monitoring of planetary health and species-specific management in changing ecosystems. However, experimental knowledge of gene functions is limited to a few species, and dependencies on distantly related models. Combined with unrecognized degrees of lineage-specific gene family expansion, this means that traditional comparative methods are insufficient. Here, we clarify definitions of homology and genomic dark matter and introduce the concept of a hotspot, defined as innovations underlying the evolution of lineage-specific biology. We illustrate hotspots using molluscs having chromosome-scale genome assemblies and focus on heat-sensing TRPM channels and species living in environments of extreme heat stress (e.g., high intertidal and hydrothermal vent gastropods and bivalves). Integrating gene family, orthogroup, and domain-based methods with genomic hotspots (local paralog expansions on chromosomes), we show that conventional approaches overlook substantial amounts of species-specific gene family diversity due to limitations of distant homology detection. In contrast, local segmental duplications are often recent, lineage-specific genetic innovations reflecting emerging adaptions and can be identified for any genome. Revealed TRPM gene family diversification highlights unique neural and behavioral mechanisms that could be beneficial in predicting species resilience to heat stress. In summary, the identification of hotspots and their integration with other types of analyses illuminate evolutionary (neuro)genomic strategies that do not depend on knowledge from model organisms and unbiasedly reveal evolutionarily recent lineage-specific adaptations. This strategy enables discoveries of biological innovations across species as prospective targets for modeling, management, and biodiversity conservation.

evolutionary biology↗

bioRxiv2021

Epigenetic machinery is functionally conserved in cephalopods

Epigenetic regulatory mechanisms are divergent across the animal kingdom, yet little is known about the epigenome in non-model organisms. Unique features of cephalopods make them attractive for investigating behavioral, sensory, developmental and regenerative processes, but using molecular approaches in such studies is hindered by the lack of knowledge about genome organization and gene regulation in these animals. We combined bioinformatic and molecular analysis of Octopus bimaculoides to identify gene expression signatures for 12 adult tissues and a hatchling, and investigate the presence and pattern of DNA methylation and histone methylation marks across tissues. This revealed a dynamic gene expression profile encoding several epigenetic regulators, including DNA methylation maintenance factors that were highly conserved and functional in cephalopods, as shown by detection of 5-methyl-cytosine in multiple tissues of octopus, squid and bobtail squid. WGBS of octopus brain and RRBS from a hatchling revealed that less than 10% of CpGs are methylated, highlighting a non-random distribution in the genome of all tissues, with enrichment in the bodies of a subset of 14,000 genes and absence from transposons. Each DNA methylation pattern encompassed genes with distinct functions and, strikingly, many of these genes showed similar expression levels across tissues. In contrast to the static pattern of DNA methylation, the histone marks H3K27me3, H3K9me3 and H3K4me3 were detected at different levels in diverse cephalopod tissues. This suggests the methylome and histone code cooperate to regulate tissue specific gene expression in a way that may be unique to cephalopods.

genomics↗

bioRxiv2021

Numerous expansions in TRP ion channel diversity highlight widespread evolution of molecular sensors in animal diversification.

Transient Potential Receptor (TRP) ion channels are a diverse superfamily of multimodal molecular sensors that respond to a wide variety of stimuli, including mechanical, chemical, and thermal. TRP channels are present in most eukaryotes but best understood in mammalian, worm, and fly genetic models, where they are expressed in diverse cell-types and commonly associated with the nervous system. Here, we characterized TRP superfamily gene and genome evolution to better understand origins and evolution of molecular sensors, brains, and behavior in animals and help advance development of novel genetic technologies, like sonogenetics. We developed a flexible push-button bioinformatic and phylogenomic pipeline, GIGANTIC, that generated genome-based gene and species trees and enabled phylogenetic characterization of challenging remote homologs and distantly-related organisms deep in evolution. We identified complete sets of TRP superfamily ion channels, with over 3000 genes in 22 animal phyla and 70 species having publicly-available sequenced genomes, including 3 unicellular outgroups. We then identified clusters of TRP family members in genomes, evaluated gene models per cluster, and repaired split gene models. We also produced whole-organism PacBio transcriptomes for five species to independently validate our gene model assessment and model repairs. We find that many TRP families exhibited numerous and often extensive expansions in different phyla. Some expansions represent local clusters on respective genomes, a trend that is likely undercounted due to varied quality in genome assemblies and annotations of non-model organisms. Our work expands known TRP diversity across animals, including addition of previously uncharacterized phyla and identification of unrecognized homologs in previously characterized species.

evolutionary biology↗

bioRxiv2021

Distinct gene expression dynamics in developing and regenerating limbs

Regenerating animals have the ability to reproduce organs that were originally generated in the embryo and subsequently lost due to injury. Understanding whether the process of regeneration mirrors development is an open question in most regenerative species. Here we take a transcriptomics approach to examine to what extent leg regeneration shows the same temporal patterns of gene expression as leg development in the embryo, in the crustacean Parhyale hawaiensis. We find that leg development in the embryo shows stereotypic temporal patterns of gene expression. In contrast, global patterns of gene expression during leg regeneration show a high degree of variation, related to the physiology of individual animals. A major driver of this variation is the molting cycle. After dissecting the transcriptional signals of individual physiology from regeneration, we obtain temporal signals that mark distinct phases of leg regeneration. Comparing the transcriptional dynamics of development and regeneration we find that, although both processes use largely the same genes, the temporal patterns in which these gene sets are deployed are different and cannot be systematically aligned. HIGHLIGHTSO_LISingle-limb data on transcriptional dynamics of leg development and regeneration C_LIO_LIDeveloping embryonic legs show stereotypic transcriptional profiles C_LIO_LIRegenerating leg transcriptomes show a high degree on individual variation C_LIO_LIRegenerating leg transcriptomes are influenced by adult physiology, especially molting C_LIO_LIRegenerating leg transcriptomes reveal distinct phases of leg regeneration C_LIO_LILeg development and regeneration use overlapping sets of genes in different temporal patterns C_LI

developmental biology↗

bioRxiv2020

Targeted millisecond-scale activation of cells using non-invasive Sonogenetics

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals1-4. However, this approach is limited as it has been challenging to target specific cells within the brain or body5-8. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show that hsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to c-fos expression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate that hsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.

neuroscience↗

bioRxiv2019

Social tolerance in Octopus laqueus - a maximal entropy model

Octopus laqueus is a small tropical octopus found in Okinawa, Japan and the greater Indo-Pacific. Octopus are often viewed as solitary animals but O. laqueus live in close proximity in the wild, and will potentially encounter one another on a regular basis, raising the possibility of sociality in the species. To test for social tolerance and social repulsion in O. laqueus, animals were kept in communal tanks, and the number of dens and sex composition was varied per tank, with a set mixture of sizes and with den occupancy tracked per individual. We found that O. laqueus will socially tolerate other individuals by sharing tanks and dens, including several animals in contact and sharing a den under den-limited conditions, and with typically no loss to cannibalism or escape. However, animals also exhibit significant levels of social repulsion, and individuals often chose a solitary den when given the option. The patterns of den occupancy are observed to be consistent with a maximum entropy model. Overall, the preference to have a den is stronger than the preference to be solitary in O. laqueus, and the animals are socially tolerant of others in the tank and in a den or shelter, a first for octopuses outside mating. The relaxed disposition and social tolerance of O. laqueus make it a promising species to work with in lab, and for development into a genetic model for social behavior in octopuses.

animal behavior and cognition↗

bioRxiv2018

SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides.

ABSTRACTHuman and octopus lineages are separated by over 500 million years of evolution, and show divergent anatomical patterns of brain organization. Moreover, while humans exhibit highly complex social behaviors, octopuses are thought to be largely asocial and solitary. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species, and in many cases enable overlapping functions. Here we provide evidence that, as in humans, the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides, and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.\n\nONE SENTENCE SUMMARYHere we provide evidence that the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) increases acute social approach behaviors in Octopus bimaculoides, a finding that is paralleled by the evolutionary conservation of the SLC6A4 binding site of MDMA.

evolutionary biology↗

bioRxiv2017

Hydrogel encapsulation of living organisms for long-term microscopy

Imaging living organisms at high spatial resolution requires effective and innocuous immobilization. Long-term imaging, across development or behavioral states, places further demands on sample mounting with minimal perturbation of the organism. Here we present a simple and inexpensive method for rapid encapsulation of small animals of any developmental stage within a photocrosslinked polyethylene glycol (PEG) hydrogel, gently restricting movement within their confined spaces. Immobilized animals maintained a normal, uncompressed morphology in a hydrated environment and could be exposed to different aqueous chemicals. We focus in particular on the nematode C. elegans, an organism that is typically viewed with paralyzing reagents, nanobeads, adhesives, or microfluidic traps. The hydrogel is optically clear, non-autofluorescent, and nearly index-matched with water for use with light-sheet microscopy. We captured volumetric images of optogenetically-stimulated responses in multiple sensory neurons over 14 hours using a diSPIM light-sheet microscope, and immobilized worms were recoverable and viable after 24 hours encapsulation. We further imaged living pygmy squid hatchlings to demonstrate size scalability, characterized immobilization quality for various crosslinking parameters and identified paralytic-free conditions suitable for high-resolution single cell imaging. PEG hydrogel encapsulation enables continuous observation for hours of small living organisms, from yeast to zebrafish, and is compatible with multiple microscope mounting geometries.

bioengineering↗