Biology subjects

Ferrufino, E.

Publications and source records attributed to Ferrufino, E..

3 recordsLinked to original sources

bioRxiv2025

CRISPR screening reveals genetic regulators associated with the evolution of eye degeneration

Determining the genetic factors contributing to trait evolution is critical for understanding how and why traits evolve; however, establishing which genes underlie the evolution of complex traits remains challenging. The freshwater fish Astyanax mexicanus, a species that includes blind, cave-dwelling and eyed, surface-dwelling fish, is a powerful model for evolutionary genetics. While genetic mapping studies in this species previously identified genomic regions associated with cave-derived traits, few causative genes and genetic changes have been identified. Here, we develop methods to identify and rapidly functionally assess candidate genes in A. mexicanus, focusing on a defining trait of cave animals, eye loss. Candidate genes were identified based on whether they fell within an eye-related quantitative trait locus, were differentially expressed between surface and cave eyes, and showed evidence of positive selection in cavefish. Single-nucleus RNA-sequencing revealed that these candidate genes were expressed in multiple cell types during development, including those in different tissues of the eye. CRISPR-Cas9-based mutagenesis demonstrated that disruption of nine of these candidate genes in surface fish resulted in altered eye size. Perturbation of one of these genes, fibulin-7 (fbln7), revealed changes in eye size across multiple stages of eye development. Together, this work identified multiple genes associated with the evolution of eye degeneration in A. mexicanus. Further, this study represents a roadmap for rapid identification and functional assessment of candidate genes implicated in the evolution of traits in cavefish that can be applied to other evolutionary genetic models.

genetics↗

bioRxiv2020

A chromosome level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution.

Identifying the genetic factors that underlie complex traits is central to understanding the mechanistic underpinnings of evolution. In nature, adaptation to severe environmental change, such as encountered following colonization of caves, has dramatically altered genomes of species over varied time spans. Genomic sequencing approaches have identified mutations associated with troglomorphic trait evolution, but the functional impacts of these mutations remain poorly understood. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, and also inhabits at least 30 different caves in the region. Cave-dwelling A. mexicanus morphs are well adapted to subterranean life and many populations appear to have evolved troglomorphic traits independently, while the surface-dwelling populations can be used as a proxy for the ancestral form. Here we present a high-resolution, chromosome-level surface fish genome, enabling the first genome-wide comparison between surface fish and cavefish populations. Using this resource, we performed quantitative trait locus (QTL) mapping analyses for pigmentation and eye size and found new candidate genes for eye loss such as dusp26. We used CRISPR gene editing in A. mexicanus to confirm the essential role of a gene within an eye size QTL, rx3, in eye formation. We also generated the first genome-wide evaluation of deletion variability that includes an analysis of the impact on protein-coding genes across cavefish populations to gain insight into this potential source of cave adaptation. The new surface fish genome reference now provides a more complete resource for comparative, functional, developmental and genetic studies of drastic trait differences within a species.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genomics↗

bioRxiv2020

Repeated evolution of circadian clock dysregulation in cavefish populations

Circadian rhythms are nearly ubiquitous throughout nature, suggesting they are critical for survival in diverse environments. Organisms inhabiting environments with arrhythmic days, such as caves, offer a unique opportunity to study the evolution of circadian rhythms in response to changing ecological pressures. Here we demonstrate that the cave environment has led to the repeated disruption of the biological clock across multiple populations of Mexican cavefish, with the circadian transcriptome showing widespread reductions in rhythmicity and changes to the timing of the activation/repression of genes in the core pacemaker. Then, we investigate the function of two genes with decreased rhythmic expression in cavefish. Mutants of these genes phenocopy reductions in sleep seen in multiple cave populations, suggesting a link between circadian dysregulation and sleep reduction. Altogether, our results reveal that evolution in an arrhythmic environment has resulted in dysregulation to the biological clock across multiple populations by diverse molecular mechanisms.

evolutionary biology↗