Evidence for holocentric centromeres in the early branching apicomplexan parasite Cryptosporidium parvum
- 1Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, United States of America
Abstract
During its asexual cycle, Cryptosporidium parvum (C. parvum) amplifies through three rounds of nuclear division before undergoing cytokinesis to form infectious merozoites. However, chromosome organization and segregation during nuclear division remain poorly studied. Here, we visualized H3-histones, including the centromeric histone H3 (CENH3), telomeres, and centrosomes during mitosis. Nuclear division was accompanied by centrosome duplication and elongated microtubules that spanned the dividing nuclei. Surprisingly, C. parvum centromeres detected by CENH3 showed diffuse staining throughout nuclear division and overlapped with telomeres in the apical nucleus. Analysis of centromeres based on CENH3 capture and DNA sequencing revealed numerous distinct binding sites scattered across all eight chromosomes, including both coding regions and intergenic regions, which were typified by GA rich repeat sequences. The unique holocentric chromosome structure of C. parvum is unlike the single regional centromeres found in related apicomplexans, suggesting it arose independently from other known examples in plants, insects and worms. Author summary: Cryptosporidium parvum is a widespread cause of diarrheal disease worldwide, and lack of knowledge about its basic biology has hindered progress to develop more effective treatments. Unlike most organisms, C. parvum divides its chromosomes within an intact nucleus and during this process, its chromosomes remain in a relaxed, uncondensed state, making the division processes difficult to visualize. Here, we used advanced imaging and genomic fingerprinting to examine how chromosomes are positioned and segregated during replication. We discovered that instead of having a single attachment point, known as the centromere, on each chromosome, C. parvum distributes hundreds of small attachment sites along all eight chromosomes. These dispersed sites remain diffuse throughout mitosis and overlap with telomeres at the chromosomes ends, revealing a chromosome organization known as holocentricity. This architecture has been described in certain plants, insects, and nematodes but has not previously been identified in protists. By defining this unusual centromere architecture, our work provides new insight into how C. parvum maintains genome stability during rapid, repeated rounds of nuclear division.
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BibTeX
@article{kimball2026evidence,
title = {{Evidence for holocentric centromeres in the early branching apicomplexan parasite Cryptosporidium parvum}},
author = {Abigail Kimball and Wanyi Huang and Melanie Key and Rui Xu and Lisa Funkhouser-Jones and L. David Sibley},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014708},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014708},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evidence for holocentric centromeres in the early branching apicomplexan parasite Cryptosporidium parvum
AU - Abigail Kimball
AU - Wanyi Huang
AU - Melanie Key
AU - Rui Xu
AU - Lisa Funkhouser-Jones
AU - L. David Sibley
PY - 2026
DA - 2026/10/26
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014708
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014708
AB - During its asexual cycle, Cryptosporidium parvum (C. parvum) amplifies through three rounds of nuclear division before undergoing cytokinesis to form infectious merozoites. However, chromosome organization and segregation during nuclear division remain poorly studied. Here, we visualized H3-histones, including the centromeric histone H3 (CENH3), telomeres, and centrosomes during mitosis. Nuclear division was accompanied by centrosome duplication and elongated microtubules that spanned the dividing nuclei. Surprisingly, C. parvum centromeres detected by CENH3 showed diffuse staining throughout nuclear division and overlapped with telomeres in the apical nucleus. Analysis of centromeres based on CENH3 capture and DNA sequencing revealed numerous distinct binding sites scattered across all eight chromosomes, including both coding regions and intergenic regions, which were typified by GA rich repeat sequences. The unique holocentric chromosome structure of C. parvum is unlike the single regional centromeres found in related apicomplexans, suggesting it arose independently from other known examples in plants, insects and worms. Author summary: Cryptosporidium parvum is a widespread cause of diarrheal disease worldwide, and lack of knowledge about its basic biology has hindered progress to develop more effective treatments. Unlike most organisms, C. parvum divides its chromosomes within an intact nucleus and during this process, its chromosomes remain in a relaxed, uncondensed state, making the division processes difficult to visualize. Here, we used advanced imaging and genomic fingerprinting to examine how chromosomes are positioned and segregated during replication. We discovered that instead of having a single attachment point, known as the centromere, on each chromosome, C. parvum distributes hundreds of small attachment sites along all eight chromosomes. These dispersed sites remain diffuse throughout mitosis and overlap with telomeres at the chromosomes ends, revealing a chromosome organization known as holocentricity. This architecture has been described in certain plants, insects, and nematodes but has not previously been identified in protists. By defining this unusual centromere architecture, our work provides new insight into how C. parvum maintains genome stability during rapid, repeated rounds of nuclear division.
SN - 1553-7374
ER -