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Cited by 2Telomeres, Telomerase, and SenescenceChromosomal and Genetic VariationsGenetics, Aging, and Longevity in Model Organisms

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Robust Binding Capability and Occasional Gene Loss of Telomere-Binding Proteins Underlying Telomere Evolution in Nematoda

Open access
Song, Hobum, Kim, Seonhong, Lim, Daisy Sunghee, Choi, Hee-Jung, Lee, Junho·2025·Genome Biology and Evolution
DOI 10.1093/gbe/evaf085PMC PMC12084805

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Abstract

Telomeres, the nucleoprotein complexes that protect the ends of linear chromosomes, are essential for maintaining the stability of eukaryotic genomes. As telomeres generally consist of repetitive DNA associated with specifically bound proteins, telomeric repeat motifs are thought to be difficult to evolve. However, a recent study identified nematodes with telomeric repeats distinct from the canonical TTAGGC motif. Here, we investigated how telomere repeats could have evolved despite the challenge posed by the specificity of telomere-binding proteins (TBPs) to the telomeric DNA in Nematoda. We performed a phylogenetic analysis and electrophoresis mobility shift assays to assess the binding affinities of two TBPs, which displayed different conservation patterns. Our results revealed that the well-conserved protein CEH-37 exhibits limited specificity, unable to distinguish telomeric repeats found in nematodes except for the TTAGGG motif, while the less conserved POT proteins displayed rigid specificity. These findings suggest that the emergence of novel telomeric repeat motifs correlated with the characteristics and evolutionary outcomes of TBPs in Nematoda. Our study not only revealed the dynamics of telomere evolution but also enhanced the understanding of the evolutionary relationship between proteins and DNAs.

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Figures

Fig. 1. Conservation of TBPs in nematodes and their phylogenetic relationships. a) Heatmap illustrating the conservation of C. elegans TBPs in various nematodes according to bit scores of BLASTP. For nematodes with noncanonical TRMs, the TRMs are indicated in brackets after the species names. Nematodes with a canonical TTAGGC TRM are not explicitly labeled. dsTBP, double-stranded telomeric DNA-binding protein; ssTBP, single-stranded telomeric DNA-binding protein. b) Phylogenetic tree of clade IV nematodes, shown at the family level. The phylogenetic tree of Panagrolaimidae, the only taxon that involves various species with a noncanonical TRM, is depicted in more detail, with Steinernema glaseri as an outgroup.
Fig. 1. Conservation of TBPs in nematodes and their phylogenetic relationships. a) Heatmap illustrating the conservation of C. elegans TBPs in various nematodes according to bit scores of BLASTP. For nematodes with noncanonical TRMs, the TRMs are indicated in brackets after the species names. Nematodes with a canonical TTAGGC TRM are not explicitly labeled. dsTBP, double-stranded telomeric DNA-binding protein; ssTBP, single-stranded telomeric DNA-binding protein. b) Phylogenetic tree of clade IV nematodes, shown at the family level. The phylogenetic tree of Panagrolaimidae, the only taxon that involves various species with a noncanonical TRM, is depicted in more detail, with Steinernema glaseri as an outgroup.CC BY-NC · PubMed Central
Fig. 2. Conservation of CEH-37 homeodomains from species with different telomeric repeat motifs and their binding affinities from Caenorhabditis species. a) The multiple sequence alignment result of CEH-37 homeodomains from nematodes used in this study. Each residue is shaded according to its degree of conservation. The α-helix regions of the domain are indicated above the multiple sequence alignment, and conserved residues involved in nucleic acid binding are indicated with hash-marks (#). b) Representative images of EMSA demonstrating the binding of the C. elegans and C. uteleia CEH-37 homeodomains to double-stranded telomeric DNAs. Five nanomolars of DNA probes indicated under each figure were incubated with increasing concentrations of proteins ranging from 5 to 160 nm. TRMs of each species are shown under their names. c and d) Kd of C. elegans and C. uteleia CEH-37 homeodomains to each telomeric DNA, respectively. DNA probes used for the Kd measurements consist of two repeats of the indicated sequences. Relationships without asterisks indicate nonsignificant differences (Newman–Keuls multiple comparison test, *P < 0.05).
Fig. 2. Conservation of CEH-37 homeodomains from species with different telomeric repeat motifs and their binding affinities from Caenorhabditis species. a) The multiple sequence alignment result of CEH-37 homeodomains from nematodes used in this study. Each residue is shaded according to its degree of conservation. The α-helix regions of the domain are indicated above the multiple sequence alignment, and conserved residues involved in nucleic acid binding are indicated with hash-marks (#). b) Representative images of EMSA demonstrating the binding of the C. elegans and C. uteleia CEH-37 homeodomains to double-stranded telomeric DNAs. Five nanomolars of DNA probes indicated under each figure were incubated with increasing concentrations of proteins ranging from 5 to 160 nm. TRMs of each species are shown under their names. c and d) Kd of C. elegans and C. uteleia CEH-37 homeodomains to each telomeric DNA, respectively. DNA probes used for the Kd measurements consist of two repeats of the indicated sequences. Relationships without asterisks indicate nonsignificant differences (Newman–Keuls multiple comparison test, *P < 0.05).CC BY-NC · PubMed Central
Fig. 3. Binding affinity of CEH-37 homeodomains from clade IV nematodes. a) Representative images of EMSA demonstrating the binding of the LJ2400, LJ2284, and S. ratti CEH-37 homeodomains to double-stranded telomeric DNAs. Five nanomolars of DNA probes indicated under each figure were incubated with increasing concentrations of proteins ranging from 5 to 160 nm for LJ2284 and S. ratti CEH-37 homeodomains, while the concentration range of the LJ2400 protein was 2.8 to 90 nm. TRMs of each species are shown under their names. b to d) Kd of CEH-37 homeodomains from LJ2400, LJ2284, and S. ratti binding to each telomeric DNA, respectively. DNA probes used for the Kd measurements consist of two repeats of the indicated sequences. Relationships without asterisks indicate nonsignificant differences (Newman–Keuls multiple comparison test, *0.01 < P < 0.05, **0.005 < P < 0.01, ***P < 0.005).
Fig. 3. Binding affinity of CEH-37 homeodomains from clade IV nematodes. a) Representative images of EMSA demonstrating the binding of the LJ2400, LJ2284, and S. ratti CEH-37 homeodomains to double-stranded telomeric DNAs. Five nanomolars of DNA probes indicated under each figure were incubated with increasing concentrations of proteins ranging from 5 to 160 nm for LJ2284 and S. ratti CEH-37 homeodomains, while the concentration range of the LJ2400 protein was 2.8 to 90 nm. TRMs of each species are shown under their names. b to d) Kd of CEH-37 homeodomains from LJ2400, LJ2284, and S. ratti binding to each telomeric DNA, respectively. DNA probes used for the Kd measurements consist of two repeats of the indicated sequences. Relationships without asterisks indicate nonsignificant differences (Newman–Keuls multiple comparison test, *0.01 < P < 0.05, **0.005 < P < 0.01, ***P < 0.005).CC BY-NC · PubMed Central
Fig. 4. Binding affinity of C. elegans and C. uteleia POT proteins and their sequence alignment. a) Representative images of EMSA demonstrating the binding of the C. elegans POT-2, POT-3, and C. uteleia CSP31.g24055 to single-stranded telomeric DNAs. Five nanomolars of DNA probes were incubated with increasing concentrations of proteins ranging from 20 to 640 nm except for the reaction by POT-2 and POT-3 to (TTAGGC)2 probe, where the protein range was 5 to 160 nm (indicated with a box). b) The multiple sequence alignment result of OB-fold domains in POT proteins from C. uteleia and C. elegans. Each residue is shaded according to its degree of conservation. Conserved residues involved in nucleic acid binding are indicated with hash-marks (#), and the marks of residues not conserved between POT proteins from C. uteleia and C. elegans are colored in red.
Fig. 4. Binding affinity of C. elegans and C. uteleia POT proteins and their sequence alignment. a) Representative images of EMSA demonstrating the binding of the C. elegans POT-2, POT-3, and C. uteleia CSP31.g24055 to single-stranded telomeric DNAs. Five nanomolars of DNA probes were incubated with increasing concentrations of proteins ranging from 20 to 640 nm except for the reaction by POT-2 and POT-3 to (TTAGGC)2 probe, where the protein range was 5 to 160 nm (indicated with a box). b) The multiple sequence alignment result of OB-fold domains in POT proteins from C. uteleia and C. elegans. Each residue is shaded according to its degree of conservation. Conserved residues involved in nucleic acid binding are indicated with hash-marks (#), and the marks of residues not conserved between POT proteins from C. uteleia and C. elegans are colored in red.CC BY-NC · PubMed Central

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Metadata

Authors
Song, H., Kim, S., Lim, D. S., Choi, H.-J., & Lee, J.
Affiliations
Seoul National University (KR)
Corresponding author
  • Choi, Hee-Jung
  • Lee, Junho
ORCID
Venue
Genome Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2025-04-30
Volume
17
Issue
5
ISSN
1759-6653 (ISSN-L)
DOI
10.1093/gbe/evaf085
PMC
PMC12084805
OpenAlex
W4410312204
Cited by
2
References
58
Citations by year
2026: 1 · 2025: 1
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome Biology and Evolution (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Research Foundation of Korea (2020R1A2C3003352)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
telomere evolution, telomere-binding proteins, nematodes, protein-DNA binding specificity, gene loss, genome stability
MeSH terms
Animals, Nematoda, Phylogeny, Protein Binding, Telomere, Evolution, Molecular, Telomere-Binding Proteins

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