Biology subjects

X, M.

Publications and source records attributed to X, M..

8 recordsLinked to original sources

bioRxiv2026

Cave adaptation drives coordinated transcriptional remodeling across diverse cell types in the brain of a teleost fish

Adaptation of organisms to extreme environments requires dramatic phenotypic changes. Studying these changes can elucidate mechanisms underlying phenotypic differences in the context of both evolution and human disease. The Mexican tetra, Astyanax mexicanus, is a powerful model of extreme adaptation over a short evolutionary time scale. This fish species includes surface- and cave-dwelling ecotypes, with cavefish displaying many adaptations to subterranean life, including behavioral changes such as sleep loss, increased appetite, and reduced aggression. Unraveling the mechanisms underlying these changes has been challenging, presumably because they are complex traits that required coordinated changes across multiple cell types to evolve. Here, we present a spatially integrated comparative cell atlas of whole adult brains of surface and cavefish. After establishing the molecular signatures of 35 cell types, we show that cave colonization drove canalized regulatory changes to gene expression across diverse cell types. Cavefish brains show shifts in cell-type composition compared to their surface counterparts, as well as complex regulatory changes to pathways governing hypoxia response and circadian rhythm. Microglia in the cavefish brain underwent extensive transcriptional remodelling, including changes in senescence and AMPK pathways. Further, cell-cell communication analysis identified a cave-enriched ligand-receptor communication pattern centered on signals sent from glial cells to diverse populations of neurons. This atlas identifies genetic changes associated with neural and behavioral evolution and provides a resource for mechanistic studies examining brain evolution.

genomics↗

bioRxiv2026

A comparative brain atlas of Mexican cavefish identifies naturally-occurring changes in cellular composition and gene expression

Understanding how naturally occurring genetic variation shapes human health and disease is critical for improving diagnosis and treatment strategies. The Mexican cavefish, Astyanax mexicanus, represents a powerful system for evolutionary medicine, enabling investigation of naturally evolved mechanisms of resilience to disease-related traits including diabetes, obesity, insomnia, and eye loss. Larval A. mexicanus, like zebrafish, are transparent, allowing whole-brain imaging, circuit mapping, and the generation of computationally derived atlases that precisely quantify neuroanatomical differences between surface and cave populations. Developing a molecular map of brain cell types provides a foundation for identifying evolved differences in neural circuits and physiology. Here, we present a single-cell atlas of the larval cavefish brain that reveals widespread divergence in the abundance and molecular signatures of neurons and glia. Our cell type map validates known neuroanatomical differences, including a reduction of the optic tectum and expansion of the pineal gland in cavefish. We uncover substantial changes in multiple glial cell classes that are linked to neural regulation of behavior, including microglia. Analysis of differential gene expression between surface and cavefish microglia revealed enhanced genes associated with synaptic pruning and clearance of neural debris, suggesting cavefish increased microglia activity to shape brain development. We also analyzed cell types that did not classify as canonical neurons or glia and identified notable divergence in transcriptomes and cell composition, including reduced meningeal fibroblasts in cavefish and substantial transcriptional changes related to phototransduction in non-visual photoreceptors within the pineal gland. Together, these findings provide a comprehensive atlas of cell type-specific gene expression differences between A. mexicanus surface and cavefish, establishing a platform for dissecting the molecular and cellular basis of evolved disease resilience in cavefish

evolutionary biology↗

bioRxiv2026

Novel mechanisms of chemosensory adaptation to the cave environment

Smell allows animals to find food, avoid danger, and communicate through the binding of odorants to chemosensory receptors on olfactory sensory neurons. The vision-priority hypothesis predicts an antagonistic relationship between olfaction and vision, in which olfactory ability increases as visual acuity decreases along evolutionary lineages, a tradeoff that often occurs through expansion and contraction of chemosensory receptor gene families. The Mexican tetra (Astyanax mexicanus), a fish species with both sighted surface-dwelling and blind cave-dwelling populations, presents an ideal model for exploring the mechanisms underlying this tradeoff. Here we show that although cavefish can sense odorants at lower concentrations than surface fish, they do not have an expanded repertoire of chemosensory receptors, increased sensory neuron number or density, or enhanced expression of receptors compared to surface fish. Instead, cavefish have physiological adaptations to the olfactory epithelium, including more motile cilia and decreased flow rate through the olfactory pits. Pharmacological attenuation of flow rate in the olfactory pits in surface fish increased visits to the odorant source, suggesting that the reduced flow rate in cavefish is an adaptation leading to better foraging. This unexpected evolutionary path to enhanced olfaction as a compensation for loss of vision underscores the need for mechanistic understanding of comparative genomics.

evolutionary biology↗

bioRxiv2025

A pangenome framework uncovers the role of deletions in repeated evolution of cave-derived traits

Structural variants (SVs) are increasingly recognized as key contributors to adaptive evolution, yet they remain underexplored compared to single-nucleotide variation. To understand how large-scale genomic changes shape repeated evolution, we leveraged multiple levels of sequence data across the powerful evolutionary model system of the Mexican tetra fish (Astyanax mexicanus). Cavefish populations have repeatedly evolved similar and dramatic phenotypes compared to surface fish such as eye loss, pigmentation loss, and sleep loss, suggesting a potential role for loss-of-function variants in cave adaptation. We constructed one of the first pangenome graphs from a naturally evolving vertebrate, enabling comprehensive discovery of SVs among 120 fish from 11 populations. We identified over 2,400 high-confidence cave-specific deletions that are enriched in biological pathways involved in vision, metabolism, and behavior and cluster non-randomly in quantitative trait loci linked to cavefish traits. Strikingly, 67 genes harbor unique deletions between independent cavefish lineages. These reused genes show strong evidence of population-specific selection (99% are under selection, compared to 8-15% in genes lacking SVs), indicating that deletions rose in frequency through repeated positive selection rather than drift. Together, these results reveal that recurrent deletion events have repeatedly contributed to the evolution of cave-adapted phenotypes and highlight deletions as underexplored contributors of adaptive evolution in a system characterized by trait loss.

evolutionary biology↗

bioRxiv2025

Hybridization Reveals Cell Type-Specific Regulatory Variation Driving Brain Transcriptomic Divergence

Gene expression is a molecular trait that can cumulatively contribute to more complex phenotypes. Interspecies hybrids have long been used to study the genetics basis of molecular, morphological and behavioral traits, to dissect interactions between cis- and trans-regulators with parental traits, and to uncover incompatible genetic interactions that drive extreme phenotypes in hybrid progeny. However, it remains unclear how organ functions at molecular level are affected by hybridization. We hypothesize that hybridization incited molecular level changes are cell type specific. To test this, we produced interspecies hybrid progeny from two distantly related fish species, Xiphophorus maculatus and couchianus. They are differing in mating, foraging behavior and likely neural circuits for cognition. We first performed allelic expression and bulk brain transcriptome profiling to identify expression quantitative trait loci (eQTLs) and quantitative transcript traits (QTTs) in order to quantify the scale and identify of loci contributing to gene expression variations in hybrids. It showed that QTT are predominantly influenced by additive eQTLs. Subsequently, we compared QTTs, which exemplify species-specific regulatory effects on gene expression, to cell type markers derived from single-nucleus RNA sequencing (snRNAseq). We identified 14 cell type-specific QTTs with known roles in brain functions. Overall, this study shows that transcriptomic phenotypes under species-specific regulators are associated to specific cell types in hybrids, and indicates the overall organ-level functional change could be driven by particular cell types.

genetics↗

bioRxiv2025

Comparison of Human Melanoma Single Cell Profiles to Evolutionary Medicine Model Xiphophorus Provides Insights In Disease Control

Melanoma remains one of the deadliest forms of cancer. Despite recent therapeutic advances including immune checkpoint inhibitors and small-molecule kinase inhibitors, patients frequently develop treatment resistance. Novel models are needed to devise strategies that overcome resistance and further reduce melanoma-related mortality. Interspecies hybrid fish from the Xiphophorus lineage develop mutant Epidermal Growth Factor Receptor (EGFR)-driven melanomas that display morphology, bulk gene expression, disease initiation and progression processes mimicking those of human melanomas. These similarities have enabled their comparative use in evaluating why human melanomas exhibit cancer cell plasticity, including dynamic transitions between proliferative and invasive states. However, it remains unclear whether Xiphophorus melanomas recapitulate some or all of these features. To address this, we performed single-nucleus RNA sequencing (snRNAseq) analysis of Xiphophorus melanomas. Multiple cancer cell types mirroring the human melanoma cell populations were identified, including proliferative cancer cells, dedifferentiated neural crest-like cells, mesenchymal-like cancer cells in addition to fibroblast, endothelial, and immune cells. Employing comparative analyses with results from human melanoma studies, it is demonstrated that Xiphophorus melanomas faithfully mimic the cellular heterogeneity observed in human melanoma.

genetics↗

bioRxiv2023

Astyanax mexicanus surface and cavefish chromosome-scale assemblies for trait variation discovery

The ability of organisms to adapt to sudden extreme environmental changes produces some of the most drastic examples of rapid phenotypic evolution. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, but repeated colonizations of cave environments have resulted in the independent evolution of troglomorphic phenotypes in several populations. Here, we present three chromosome-scale assemblies of this species, for one surface and two cave populations, enabling the first whole-genome comparisons between independently evolved cave populations to evaluate the genetic basis for the evolution of adaptation to the cave environment. Our assemblies represent the highest quality of sequence completeness with predicted protein-coding and non-coding gene metrics far surpassing prior resources and, to our knowledge, all long-read assembled teleost genomes, including zebrafish. Whole genome synteny alignments show highly conserved gene order among cave forms in contrast to a higher number of chromosomal rearrangements when compared to other phylogenetically close or distant teleost species. By phylogenetically assessing gene orthology across distant branches of amniotes, we discover gene orthogroups unique to A. mexicanus. When compared to a representative surface fish genome, we find a rich amount of structural sequence diversity, defined here as the number and size of insertions and deletions as well as expanding and contracting repeats across cave forms. These new more complete genomic resources ensure higher trait resolution for comparative, functional, developmental, and genetic studies of drastic trait differences within a species.

genomics↗

bioRxiv2023

Candidate Genes Associated with Parity Mode Evolution are Under Selection in Oviparous and Viviparous Snakes

Over 100 divergent lineages of squamates are viviparous (live-bearing) while others are oviparous (egg-laying). Estimated origins of oviparity and viviparity across the squamate phylogeny are a subject of scientific debate. Identifying genomic changes that influence parity mode evolution can provide insights on the adaptive nature of both parity modes. Using BUSTED in the HyPhy suite and whole genomes of 27 species of snakes, I test for gene-wide episodic diversifying selection (EDS) in 1,587 candidate genes. The genomes represent 14 viviparous and 13 oviparous species across four families (Viperidae, Elapidae, Natricidae, and Pythonidae), including eight new genomes from Lachesis muta, Lachesis stenophrys, Agkistrodon contortrix, Trimeresurus albolabris, Gloydius halys, Ophryacus undulatus, Ovophis monticola, and Calloselasma rhodostoma. Candidate genes were chosen based on evidence for their involvement of seven physiological processes expected to change during evolutionary transitions between parity modes. EDS was measured across candidate gene trees under different foreground branch tests: 1) all viviparous branches, 2) viviparous Viperidae branches, 3) viviparous Elapidae and Natricidae branches, 4) all oviparous branches, and 5) oviparous Viperidae branches (estimated reversals). Over 16% of tests found evidence for EDS, translating to 533 genes with EDS associated with parity mode. Some genes had significant EDS in multiple tests. However, the all oviparous test identified a 2.8 to 5.9-fold increase in the number of unique genes with EDS compared to other foreground tests. These results suggest that EDS may influence the evolution of both oviparity and viviparity. Future research using population-level data from snakes may further elucidate the role of selection in parity mode evolution.

evolutionary biology↗