Biology subjects

Virani, M.

Publications and source records attributed to Virani, M..

3 recordsLinked to original sources

bioRxiv2025

Convergence and conflict among telomere specialized transposons across 60 million years of Drosophilid evolution

The Drosophila telomere is one of the best-studied examples of active transposable elements (TEs) benefitting, rather than harming, a host genome. All Drosophila species lack telomerase and instead have telomeres composed of head-to-tail arrays of specialized retrotransposons. These TEs ostensibly act as mutualists by elongating chromosome ends, but evidence from species closely related to Drosophila melanogaster suggests that telomeric transposons may also antagonize their host genome. Importantly, the limited number of Drosophila species characterized thus far has precluded our ability to delineate idiosyncratic from universal evolutionary forces and genetic mechanisms that shape the history of these TEs. Here, we have surveyed long-read genome assemblies of over 100 species of Drosophila, identifying a total of 396 telomeric TE families. Our findings show that these telomere-specialized elements evolve rapidly and also undergo striking convergent evolution: the complete loss of telomeric TEs has occurred repeatedly across the genus while individual telomeric TE lineages have repeatedly lost one of their two protein-coding genes. These elements have also repeatedly undergone horizontal transfer between distantly related Drosophila lineages and have repeatedly captured host gene fragments that promote their selfish suppression of host TE-silencing systems. Furthermore, telomere specialization itself appears to have evolved convergently, as some non-telomeric families have gained the ability to target their insertions to telomeres. These results provide unprecedented resolution into the evolution of these unusual TEs and highlight several novel mechanisms by which they evolve in conflict both with each other and their host genome despite the essential telomere function they provide.

genomics↗

bioRxiv2024

Parkinson's disease-associated shifts between DNA methylation and DNA hydroxymethylation in human brain

Epigenetic mechanisms are mediators of interactions between aging, genetics, and environmental factors in sporadic Parkinsons disease (PD). Multiple studies have explored the DNA modifications in PD, but few focus on 5-hydroxymethylcytosine (5-hmC), which is important in the central nervous system and sensitive to environmental exposures. To date, studies have not differentiated between 5-methylcytosine (5-mC) and 5-hmC or have analyzed them separately. In this study, we modeled paired 5-mC and 5-hmC data simultaneously. We identified 108 cytosines with significant PD-associated shifts between these marks in an enriched neuronal population from PD postmortem parietal cortex, within 83 genes and 34 enhancers associated with 67 genes. These data potentially link epigenetic regulation of genes related to LRRK2 and endolysosomal sort (RAB32 and AGAP1), and genes involved in neuroinflammation, the inflammasome, and neurodevelopment with early changes in PD and suggest that there are significant shifts between 5mC and 5hmC associated with PD in genes not captured by standard methods.

neuroscience↗

bioRxiv2024

Developmental origins of Parkinson's disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinsons disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the -synuclein preformed fibril (-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points - birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late life diseases, including PD.

neuroscience↗