Biology subjects

Boswell, W.

Publications and source records attributed to Boswell, W..

5 recordsLinked to original sources

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

The Growth of Xiphophorus hellerii is Negatively Correlated with Colony Density

Xiphophorus fishes serve as important animal models in biomedical research. To investigate colony density influence on growth, we compared 6-, 9-, and 12-month-old fish raised in low- (1 fish/2L), mid- (1 fish/L), and high-density (2 fish/L) in re-circulating aquariums. As expected, the results indicate that fish reared in low-density aquariums exhibit the greatest growth, and fish reared in high-density aquariums result in the least growth.

zoology↗

bioRxiv2025

A Recessive oca2 Mutation Underlies Albinism in Xiphophorus fish

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by impaired melanin production, leading to reduced pigmentation in the skin, hair, and eyes. Xiphophorus, a genus of small freshwater fish, has been a pivotal model organism in pigmentation disorder research, providing key findings in the genetic pathways governing physiological and pathological pigment cell biology. Leveraging the well-established research framework provided by Xiphophorus, we have identified a spontaneously occurring albinism phenotype in swordtail fish Xiphophorus hellerii. Genetic mapping of albino fish showed that albinism is associated with a recessive mutation in the oca2 gene. This discovery provides a novel opportunity to explore functions of oca2 gene in pigment cell differentiation, pigment synthesis, melanosome assembly and transportation function and amelanotic melanoma development.

genetics↗

bioRxiv2024

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility. SignificanceThe Dobzhansky-Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky-Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.

genetics↗

bioRxiv2022

Transcriptional background effects on a tumor driver gene in a transgenic medaka melanoma model

The Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka, but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect, and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk-driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk-driven tumors, and compared (1) genes that are co-expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell type-specific transcriptomes. Melanoma tumors exhibited gene signatures that are relevant to proliferation and invasion while xanthoerythrophoroma tumors are characterized by expression profiles related metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell-type specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.

genetics↗