Biology subjects

Saccas, M.

Publications and source records attributed to Saccas, M..

4 recordsLinked to original sources

bioRxiv2024

Reconstructing the dynamics of past coral endosymbiotic algae communities using coral ancient DNA (coraDNA)

Most scleractinian corals are drastically threatened due to global changes but some colonies are intriguingly resistant to heat stress. Coral thermal tolerance partly relies on genomic determinism among the cnidarian compartment but also on the physiology of their associated symbiotic algae (Symbiodiniaceae). In fact, some corals can shift and/or shuffle their associated Symbiodiniaceae communities to temporally cope with heat stress. So far coral adjustments of their endosymbiotic algae were mainly observed at short-term evolutionary time scales and we lack a general vision of coral holobiont evolution at broader timescales. We here combined the use of ancient DNA from a coral core and a metabarcoding approach, to retrace past Symbiodiniaceae communities associated with a living colony of Porites lobata from New Caledonia over the last century. We were able to extract ancient DNA along the coral core at 19 time points dating back to the 1870s. Overall, we detected 13 OTUs, nine of which were affiliated to the Symbiodiniaceae Cladocopium clade, one to Azadinium spinosum (Dinophycae); one to the host P. lobata, the two other OTUs remained unidentified. One OTU was largely predominant and was ubiquitous over all samples. The number of OTUs was marginally correlated to the total number of sequences per sample but not to the age of the coraDNA sample. We found a generally stable core microbiota associated with P. lobata, although drastic change in community composition was observed in coraDNA samples corresponding to an extreme hot winter temperature event. More generally, this study paves the way for further investigations on the evolutionary dynamics of coral holobionts at the colony level over large temporal scales.

evolutionary biology↗

bioRxiv2023

Epigenetic then genetic variations underpin rapid adaptation of oyster populations (Crassostrea gigas) to Pacific Oyster Mortality Syndrome (POMS)

Disease emergence is accelerating in response to human activity-induced global changes. Understanding the mechanisms by which host populations can rapidly adapt to this threat will be crucial for developing future management practices. Pacific Oyster Mortality Syndrome (POMS) imposes a substantial and recurrent selective pressure on oyster populations (Crassostrea gigas). Rapid adaptation to this disease may arise through both genetic and epigenetic mechanisms. In this study, we used a combination of whole exome capture of bisulfite-converted DNA, next-generation sequencing, and (epi)genome-wide association mapping, to show that natural oyster populations differentially exposed to POMS displayed signatures of selection both in their genome (single nucleotide polymorphisms) and epigenome (CG-context DNA methylation). Consistent with higher resistance to POMS, the genes targeted by genetic and epigenetic variations were mainly related to host immunity. By combining correlation analyses, DNA methylation quantitative trait loci, and variance partitioning, we revealed that a third of the observed phenotypic variation was explained by interactions between the genetic sequence and epigenetic information, [~]14% by the genetic sequence, and up to 25% by the epigenome alone. Thus, as well as genetic adaptation, epigenetic mechanisms governing immune responses contribute significantly to the rapid adaptation of hosts to emerging infectious diseases.

evolutionary biology↗

bioRxiv2022

The crosstalk between DNA-PK and cGAS drives tumor immunogenicity

Cytosolic DNAs promote inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been thus suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that lack cGAS to question whether alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex drives cGAS independent inflammatory responses but that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment, a process that impaired early tumorigenesis but correlated with poor outcome. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.

cancer biology↗

bioRxiv2020

Control of polyunsaturated fatty acids desaturation by Sting regulates inflammatory responses

Inflammatory disorders are major health issues in which immune function and metabolic homeostasis are concertedly altered. Yet, the molecular mechanisms coordinating innate and metabolic pathways in homeostatic conditions are poorly understood. Here, we unveil a negative regulatory feedback loop involving the Stimulator of interferon genes (Sting) and the Fatty acid desaturase 2 (Fads2). At steady state, Sting regulates FA metabolism by repressing the activity of the Fads2 enzyme responsible for the desaturation of polyunsaturated FAs (PUFAs). Importantly, Sting activation increased Fads2 activity, while antagonizing Fads2 enhanced Sting activation, promoting the establishment of an anti-viral state. Remarkably, the cross-regulation between Sting and Fads2 is mediated by the cyclic GMP-AMP (cGAMP) Sting agonist and PUFAs. Indeed, we found that PUFAs inhibit Sting activation, while Sting agonists bind Fads2. Thus, our study identifies Sting as a master regulator of FA metabolism, and PUFAs as modulators of Sting-dependent inflammation. The interplay between Fads2 and Sting determines the fine-tuning of inflammatory responses, but comes at the expense of metabolic alterations, which are critical to consider in human pathologies associated with aberrant Sting activation.

immunology↗