Kapatral, V. | bioRxiv Science

bioRxiv2025

Epigenomic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan

Giant tortoises exhibit exceptional longevity, often exceeding the human lifespan. To understand the genomic and epigenomic basis of their longevity, awe analyzed the DNA sequence and methylome of Jonathan, an Aldabra giant tortoise (Aldabrachelys gigantea), estimated to be 192 years old. Relative to other giant tortoises (Aldabrachelys gigantea and Chelonoidis abingdonii), we found Jonathan has gene variants in pathways associated with aging, including DNA repair and telomere regulation. Consistent with his advanced age, Jonathan has significant age-related changes in DNA methylation and methylation entropy, compared with a 5-year-old Aldabra individual. Notably, we found that low entropy regions in Jonathans methylome were enriched for genes involved in the electron transport chain. This suggests that high-fidelity transcription of these genes may be crucial for extreme longevity. With this data, we propose a model for aging, that links efficient mitochondrial energy production with nuclear maintenance of low methylation entropy.

genomics↗

bioRxiv2023

A correlative study of the genomic underpinning of virulence traits and drug tolerance of Candida auris

Candida auris is an opportunistic fungal pathogen with high mortality rates that presents a clear and present threat to public health. The risk of C. auris infection is high because it can colonize the body, resist antifungal treatment, and evade the immune system. The genetic mechanisms for these traits are not well-known. Identifying them could lead to new targets for new treatments. To this end, we present an analysis of the genetics and gene expression patterns of C. auris carbon metabolism, drug resistance, and macrophage interaction. We chose to study two C. auris isolates simultaneously, one drug sensitive (B11220 from Clade II) and one drug resistant (B11221 from Clade III). Comparing the genomes, we found that B11220 was missing a 12.8 kb gene cluster encoding proteins related to alternative sugar utilization, possibly L-rhamnose. We show that B11221, which has the cluster, more readily assimilates and utilizes D-galactose and L-rhamnose. B11221 also exhibits increased adherence and drug resistance compared to B11220 when grown in these sugars. Transcriptomic analysis of both strains grown on glucose or galactose showed that genes associated with translation were upregulated in B11221, and the putative L-rhamnose gene cluster was upregulated when grown on D-galactose. These findings reinforce the growing evidence of a link between metabolism and tolerance. Since immune system evasion depends heavily on the cell surface, we characterized cell wall composition and macrophage evasion for the two strains. We found that B11221 has far less {beta}-1,3-glucan exposure, a key determinant of immune system evasion, and resists phagocytosis by macrophages compared to B11220. In a transcriptomic analysis of both strains co-cultured with macrophages we found that B11221 upregulates genes associated with early stages of growth and transcription factors that regulate transport. These key differences in growth and membrane composition could explain the resistance to phagocytosis and increased stress tolerance in general of B11221, and indicates another connection between metabolism and immune system evasion. Taken together, these data show that membrane composition, metabolism, and transport all correlate with colonization, drug resistance, and immune system evasion in C. auris.

microbiology↗