Biology subjects

X, M.

Publications and source records attributed to X, M..

3 recordsLinked to original sources

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↗