Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1137985 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29896633.fastq.gz | Fastqsanger.gz | |||
| SRR29896634.fastq.gz | Fastqsanger.gz | |||
| SRR29896635.fastq.gz | Fastqsanger.gz | |||
| SRR29896636.fastq.gz | Fastqsanger.gz | |||
| SRR29896637.fastq.gz | Fastqsanger.gz |
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Project description:Dysregulation of sleep has widespread health consequences and represents an enormous health burden. Short-sleeping individuals are predisposed to the effects of neurodegeneration, suggesting a critical role for sleep in the maintenance of neuronal health. While the effects of sleep on cellular function are not completely understood, growing evidence has identified an association between sleep loss and DNA damage, raising the possibility that sleep facilitates efficient DNA repair. The Mexican tetra fish,Astyanax mexicanusprovides a model to investigate the evolutionary basis for changes in sleep and the consequences of sleep loss. Multiple cave-adapted populations of these fish have evolved to sleep for substantially less time compared to surface populations of the same species without identifiable impacts on healthspan or longevity. To investigate whether the evolved sleep loss is associated with DNA damage and cellular stress, we compared the DNA Damage Response (DDR) and oxidative stress levels betweenA. mexicanuspopulations. We measured markers of chronic sleep loss and discovered elevated levels of the DNA damage marker γH2AX in the brain, and increased oxidative stress in the gut of cavefish, consistent with chronic sleep deprivation. Notably, we found that acute UV-induced DNA damage elicited an increase in sleep in surface fish but not in cavefish. On a transcriptional level, only the surface fish activated the photoreactivation repair pathway following UV damage. These findings suggest a reduction of the DDR in cavefish compared to surface fish that coincides with elevated DNA damage in cavefish. To examine DDR pathways at a cellular level, we created an embryonic fibroblast cell line from the two populations ofA. mexicanus. We observed that both the DDR and DNA repair were diminished in the cavefish cells, corroborating thein vivofindings and suggesting that the acute response to DNA damage is lost in cavefish. To investigate the long-term impact of these changes, we compared the transcriptome in the brain and gut of aged surface fish and cavefish. Strikingly, many genes that are differentially expressed between young and old surface fish do not transcriptionally vary by age in cavefish. Taken together, these findings suggest that have developed resilience to sleep loss, despite possessing cellular hallmarks of chronic sleep deprivation.
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Project description:Circadian rhythm disruption is associated with skeletal muscle dysfunction within the blind Mexican Cavefish
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Project description:We report the shift in skeletal muscle investment strategies of the Mexican cavefish following cave colonization
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Project description:Circadian disruption underlies skeletal muscle dysfunction within the Mexican Cavefish
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Project description:Interactions between sleep and feeding behaviors are critical for adaptive fitness. Diverse species suppress sleep when food is scarce to increase the time spent foraging. Postprandial 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 the effects of feeding on sleep in larval and adult surface fish, and in 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, which 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.
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Project description:This study seeks to investigate genome-wide, circadian-regulated gene expression within the skeletal muscle of the Astyanax mexicanus – comprised of the river-dwelling surface fish and troglobitic cavefish – providing novel insights into the evolutionary consequence of circadian disruption on skeletal muscle physiology
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Project description:Reduced parasitic infection rates in the developed world are suspected to underlie the rising prevalence of autoimmune disorders. However, the long-term evolutionary consequences of decreased parasite exposure on an immune system are not well understood. We used the Mexican tetra Astyanax mexicanus to understand how loss of parasite diversity influences the evolutionary trajectory of the vertebrate immune system, by comparing river with cave morphotypes. Here, we present field data affirming a strong reduction in parasite diversity in the cave ecosystem, and show that cavefish immune cells display a more sensitive pro-inflammatory response towards bacterial endotoxins. Surprisingly, other innate cellular immune responses, such as phagocytosis, are drastically decreased in cavefish. Using two independent single-cell approaches, we identified a shift in the overall immune cell composition in cavefish as the underlying cellular mechanism, indicating strong differences in the immune investment strategy. While surface fish invest evenly into the innate and adaptive immune systems, cavefish shifted immune investment to the adaptive immune system, and here, mainly towards specific T-cell populations that promote homeostasis. Additionally, inflammatory responses and immunopathological phenotypes in visceral adipose tissue are drastically reduced in cavefish. Our data indicate that long-term adaptation to low parasite diversity coincides with a more sensitive immune system in cavefish, which is accompanied by a reduction in the immune cells that play a role in mediating the pro-inflammatory response.
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Project description:We found higher substitution rates in cavefish compared with surface fish, in accordance with a smaller cavefish population size which has allowed more rapid fixation of derived alleles present in the ancestral population. This result also implies that the Pachn cave population is much younger than previously estimated. The comparison of these data with simulations suggests that the Pachn cavefish population has probably been underground less than 30,000 years. This new time frame, together with other evidence, indicate that the evolution of cave phenotypes mainly involves the fixation of cryptic genetic variants present in surface fish populations within a short period of time.
2016-06-27 | E-MTAB-5142 | biostudies-arrayexpress
Project description:To test wheather cavefish have higher lipogenesis capability than surface fish, we used liver sample from fasted and refed fish to do RNA-seq to compare their transcriptome responding to feeding in surface fish and Pachón cavefish. Moreover, we did the Pparγ ChIP-seq with liver from fed surface fish and Pachón cavefish. We amied to test whether Pparγ in Pachón cavefish have more biding sites and higher binding peaks than surface fish.
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