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O'Gorman, M.

Publications and source records attributed to O'Gorman, M..

4 recordsLinked to original sources

Cave evolution on repeat: reuse of the same genomic regions across lineages but not across traits in Astyanax mexicanus

Similar traits repeatedly evolve across independent populations in response to similar environmental conditions. For many repeatedly evolved traits it is unknown if populations evolve similar traits through the same or different genetic mechanisms. To address this question, we leveraged the Mexican tetra fish, Astyanax mexicanus, which has evolved repeatedly through altering many traits including reduced sleep duration, eye degeneration, and metabolic shifts to accommodate limited nutrient availability. We defined whether shared or independent genetic architecture govern the repeated evolution of sleep loss, increased food consumption, early onset adipose deposition, and eye loss in different evolutionary origins of the cavefish phenotype by using Quantitative Trait Locus (QTL) mapping across three cave x surface F2 mapping populations. We found that, among the traits evaluated, eye loss exhibits the most genetic repeatability, with [~]43% of QTL shared across lineages. Sleep loss and metabolic traits (i.e., feeding, adiposity) were genetically less repeatable, with only [~]25-33% of QTL shared across lineages. Next, we explored whether QTL for metabolism, eye loss, and sleep traits in cavefish co-localize in the cavefish genome and could be inherited together to facilitate potential cavefish adaptation. Although these traits have repeatedly co-evolved in cave populations, we did not find evidence for extensive genetic linkage among them. Overall, we found that genetic repeatability is a common feature in the repeated evolution of cave traits, the extent of genetic repeatability varies across cave traits, and that there is little evidence for widespread co-localization of sleep, eye loss, and metabolic traits within the genome. SummaryIndependent populations that evolve similar traits in response to similar environmental conditions provide us with natural replicates for studying what constrains evolutionary change. Iconic examples of repeated trait evolution often involve repeated mutations in the same genes, suggesting there are limits on the type of genes and mutations that can contribute to phenotypic evolution. Here we conduct a multi-trait, multi-population QTL analysis for similar eye loss, sleep loss and metabolic shifts across two lineages of Astyanax mexicanus. Genetic repeatability is present for most traits, but its extent is highly trait dependent and occurs at the level of genomic regions rather than specific genes, highlighting the mosaic of constraint and flexibility involved in genetic repeatability.

evolutionary biology↗

Postprandial sleep in short-sleeping Mexican cavefish

Interaction between sleep and feeding behaviors are critical for adaptive fitness. Diverse species suppress sleep when food is scarce to increase the time spent foraging. Post-prandial sleep, an increase in sleep time following a feeding event, has been documented in vertebrate and invertebrate animals. While interactions between sleep and feeding appear to be highly conserved, the evolution of postprandial sleep in response to changes in food availability remains poorly understood. Multiple populations of the Mexican cavefish, Astyanax mexicanus, have independently evolved sleep loss and increased food consumption compared to surface-dwelling fish of the same species, providing the opportunity to investigate the evolution of interactions between sleep and feeding. Here, we investigate effects of feeding on sleep in larval and adult surface fish, and two parallelly evolved cave populations of A. mexicanus. Larval surface and cave populations of A. mexicanus increase sleep immediately following a meal, providing the first evidence of postprandial sleep in a fish model. The amount of sleep was not correlated to meal size and occurred independently of feeding time. In contrast to larvae, postprandial sleep was not detected in adult surface or cavefish, that can survive for months without food. Together, these findings reveal that postprandial sleep is present in multiple short-sleeping populations of cavefish, suggesting sleep-feeding interactions are retained despite the evolution of sleep loss. These findings raise the possibility that postprandial sleep is critical for energy conservation and survival in larvae that are highly sensitive to food deprivation.

neuroscience↗

Pleiotropic function of the oca2 gene underlies the evolution of sleep loss and albinism in cavefish

Adaptation to novel environments often involves the evolution of multiple morphological, physiological and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems [1,3]. The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Northeast Mexico and ancestral-like surface fish which inhabit the rivers of Mexico and Southern Texas [6]. Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits that are common to cave animals throughout the world, including albinism, eye loss, and alterations to behavior [8-10]. To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found significant differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and many other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism [11-15]. Surface fish with CRISPR-induced mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to different, independently evolved populations of albino cavefish with naturally occurring mutations in oca2, confirming that oca2 contributes to sleep loss. Finally, analysis of the oca2 locus in wild caught cave and surface fish suggests that oca2 is under positive selection in at least three cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of both of albinism and sleep loss.

evolutionary biology↗

Vascular Endothelial Growth Factor as an Immediate-Early Activator of UV-induced Skin Injury

The negative health consequences of acute ultraviolet (UV) exposure are evident, with reports of 30,000 emergency room visits annually to treat the effects of sunburn in the United States alone. Acute effects of sunburn include erythema, edema, and severe pain, and chronic overexposure to UV radiation can lead to skin cancer. While the pain associated with the acute effects of sunburn may be relieved by current interventions, existing post-sunburn treatments are not capable of reversing the cumulative and long-term pathological effects of UV exposure, an unmet clinical need. Here we show that activation of the vascular endothelial growth factor (VEGF) pathway is a direct and immediate consequence of acute UV exposure, and activation of VEGF signaling is necessary for the initiating the acute pathological effects of sunburn. In UV-exposed human subjects, VEGF signaling is activated within hours. Topical delivery of VEGF pathway inhibitors, targeted against the ligand VEGF-A (gold nanoparticles conjugated with anti-VEGF antibodies) and small molecule antagonists of VEGF receptor signaling, prevent the development of erythema and edema in UV-exposed mice. Collectively, these findings suggest targeting VEGF signaling may reduce the subsequent inflammation and pathology associated with UV-induced skin damage, which reveals a new post-exposure therapeutic window to potentially inhibit the known detrimental effects of UV on human skin.

molecular biology↗