The Rad9–Rad1–Hus1 DNA Repair Clamp is Found in Microsporidia

Santos, Anne Caroline Mascarenhas dos; Julian, Alexander Thomas; Pombert, Jean‐François

doi:10.1093/gbe/evac053

Cited by 13 publications

(14 citation statements)

References 80 publications

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“…Although we present the largest comparison of protein function between microsporidia species so far, detecting protein function from sequence alone in microsporidia is challenging. Additional analyses taking advantage of advances in structural prediction are likely to detect highly diverged proteins that would be missed based on sequence similarity alone [10,45,46]. One class of proteins that contributes to diversity between microsporidian species are the large gene families.…”

Section: Discussionmentioning

confidence: 99%

Genomic and phenotypic evolution of nematode-infecting microsporidia

Wadi

Jarkass

Tran

et al. 2022

Preprint

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Microsporidia are a large phylum of intracellular parasites that can infect most types of animals. Species in the Nematocida genus can infect nematodes including Caenorhabditis elegans, which has become an important model to study mechanisms of microsporidia infection. To understand the genomic properties and evolution of nematode-infecting microsporidia, we sequenced the genomes of nine species of microsporidia, including two genera, Enteropsectra and Pancytospora, without any previously sequenced genomes. Phylogenetic analysis shows that Nematocida is composed of two groups of species. Core cellular processes, including metabolic pathways, are mostly conserved across genera of nematode-infecting microsporidia. Each species encodes unique proteins belonging to large gene families that are likely used to interact with host cells. Most strikingly, we observed one such family, NemLGF1, is present in both Nematocida and Pancytospora species, suggesting horizontal gene transfer between species from different genera. To understand how Nematocida phenotypic traits evolved, we measured the host range, tissue specificity, spore size, and polar tube length of several species in the genus. Our results demonstrate that the ability to infect multiple tissues was likely recently lost in N. homosporus and that species with longer polar tubes are able to infect multiple tissues. Together, our work details both genomic and trait evolution between related microsporidia species and provides a useful resource for further understanding microsporidia evolution and infection mechanisms.

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Section: Discussionmentioning

confidence: 99%

Genomic and phenotypic evolution of nematode-infecting microsporidia

Wadi

Jarkass

Tran

et al. 2022

Preprint

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“…Clr4 is an integral component of CLRC, composed of Clr4, Cul4, Rik1, Pip1 and delocalization of Swi6 (Dos) protein Dos1 in S. pombe , and which is required for heterochromatin formation [ 25 ]. Components of this complex are structurally analogous to the Cullin-RING ubiquitin ligase complex Cul4/DDB1/Rbx1 (Rtt101/Mms1/Hrt1 in S. cerevisiae ) involved in DNA repair [ 42 ], and for which we previously identified several structural analogs in Encephalitozoon cuniculi [ 43 ]. Dos1 (also known as Raf1 in S. pombe ) is a DDB1–CUL4-associated factor (DCAF) forming a single 7-bladed beta-propeller [ 44 ], a common repetitive protein structure with over 20 possible structural analogs in E. cuniculi [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

“…Components of this complex are structurally analogous to the Cullin-RING ubiquitin ligase complex Cul4/DDB1/Rbx1 (Rtt101/Mms1/Hrt1 in S. cerevisiae ) involved in DNA repair [ 42 ], and for which we previously identified several structural analogs in Encephalitozoon cuniculi [ 43 ]. Dos1 (also known as Raf1 in S. pombe ) is a DDB1–CUL4-associated factor (DCAF) forming a single 7-bladed beta-propeller [ 44 ], a common repetitive protein structure with over 20 possible structural analogs in E. cuniculi [ 43 ]. Altogether, these results indicate that H3K9me epigenetic regulation is likely present in Encephalitozoon spp.…”

Section: Resultsmentioning

confidence: 99%

Telomere-to-Telomere genome assemblies of human-infecting Encephalitozoon species

et al. 2023

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Background Microsporidia are diverse spore forming, fungal-related obligate intracellular pathogens infecting a wide range of hosts. This diversity is reflected at the genome level with sizes varying by an order of magnitude, ranging from less than 3 Mb in Encephalitozoon species (the smallest known in eukaryotes) to more than 50 Mb in Edhazardia spp. As a paradigm of genome reduction in eukaryotes, the small Encephalitozoon genomes have attracted much attention with investigations revealing gene dense, repeat- and intron-poor genomes characterized by a thorough pruning of molecular functions no longer relevant to their obligate intracellular lifestyle. However, because no Encephalitozoon genome has been sequenced from telomere-to-telomere and since no methylation data is available for these species, our understanding of their overall genetic and epigenetic architectures is incomplete. Methods In this study, we sequenced the complete genomes from telomere-to-telomere of three human-infecting Encephalitozoon spp. —E. intestinalis ATCC 50506, E. hellem ATCC 50604 and E. cuniculi ATCC 50602— using short and long read platforms and leveraged the data generated as part of the sequencing process to investigate the presence of epigenetic markers in these genomes. We also used a mixture of sequence- and structure-based computational approaches, including protein structure prediction, to help identify which Encephalitozoon proteins are involved in telomere maintenance, epigenetic regulation, and heterochromatin formation. Results The Encephalitozoon chromosomes were found capped by TTAGG 5-mer telomeric repeats followed by telomere associated repeat elements (TAREs) flanking hypermethylated ribosomal RNA (rRNA) gene loci featuring 5-methylcytosines (5mC) and 5-hemimethylcytosines (5hmC), themselves followed by lesser methylated subtelomeres and hypomethylated chromosome cores. Strong nucleotide biases were identified between the telomeres/subtelomeres and chromosome cores with significant changes in GC/AT, GT/AC and GA/CT contents. The presence of several genes coding for proteins essential to telomere maintenance, epigenetic regulation, and heterochromatin formation was further confirmed in the Encephalitozoon genomes. Conclusion Altogether, our results strongly support the subtelomeres as sites of heterochromatin formation in Encephalitozoon genomes and further suggest that these species might shutdown their energy-consuming ribosomal machinery while dormant as spores by silencing of the rRNA genes using both 5mC/5hmC methylation and facultative heterochromatin formation at these loci.

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“…One limitation of our approach is orthologs are identified based on sequence identity, which can fail to identify highly divergent microsporidia orthologs (Nakjang et al 2013). Approaches in the future using structural based detection may be able to overcome this limitation (Mascarenhas dos Santos et al 2022; Svedberg et al 2023).…”

Section: Discussionmentioning

confidence: 99%

Functional consequences of reductive protein evolution in a minimal eukaryotic genome

Jiang,

Qu,

Grigorescu

et al. 2024

Preprint

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Microsporidia are parasites with the smallest known eukaryotic genomes. The extent of protein loss in these organisms has been well documented, but much less is known about how compaction of microsporidia proteins affects their function. Taking a comparative genomic approach, we identified microsporidia orthologs of budding yeast proteins and show that these orthologs are enriched for essential yeast genes. We show that the median microsporidia protein is 21% shorter than its yeast counterpart and although extensive protein loss occurred after the divergence of microsporidia, reduced protein sizes were already present in microsporidian relatives. Microsporidia proteins are shorter through reduced domain lengths, diminished linker lengths, and domain loss, with 21% of microsporidia orthologs having lost domains present in yeast. On average, 34% of microsporidia orthologs have lost C-terminal residues essential for function in yeast, including 13 essential domains lost per genome. We also found that microsporidia display distinct phylogenetic patterns of domain loss, with losses occurring in a clade-specific manner. To investigate conservation of function, we used yeast complementation assays to test orthologs from several microsporidia species and their relative Rozella allomycis. These experiments reveal that most microsporidia proteins cannot complement their yeast orthologs, the ability to complement is about three-fold less than observed for R. allomycis orthologs, and proteins that do not complement are more reduced in length than their yeast orthologs. Altogether, our results demonstrate the drastic reduction of microsporidia proteins and show that these reductions have resulted in functional divergence from their fungal ancestors.

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The Rad9–Rad1–Hus1 DNA Repair Clamp is Found in Microsporidia

Cited by 13 publications

References 80 publications

Genomic and phenotypic evolution of nematode-infecting microsporidia

Genomic and phenotypic evolution of nematode-infecting microsporidia

Telomere-to-Telomere genome assemblies of human-infecting Encephalitozoon species

Functional consequences of reductive protein evolution in a minimal eukaryotic genome

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