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The heterochromatic chromosome caps in great apes impact telomere metabolism.

Novo C, Arnoult N, Bordes WY, Castro-Vega L, Gibaud A, Dutrillaux B, Bacchetti S, Londoño-Vallejo A - Nucleic Acids Res. (2013)

Bottom Line: In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species.Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution.In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres.

View Article: PubMed Central - PubMed

Affiliation: Telomeres and Cancer laboratory, 'Equipe Labellisée Ligue contre le Cancer', UMR3244, Institut Curie, 26 rue d'Ulm, 75248 Paris, France.

ABSTRACT
In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species. Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution. Here, we show that telomeres on chromosome arms carrying subtelomeric heterochromatic caps in the chimpanzee, which are completely absent in humans, replicate later than telomeres on chromosome arms without caps. In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres. Strikingly, telomere-containing RNA accumulates extrachromosomally in gorilla mitotic cells, suggesting that at least some aspects of telomere-containing RNA biogenesis have diverged in gorilla, perhaps in concert with the evolution of heterochromatic caps in this species.

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Large telomere-like sequences detected by LNA telomeric probes replicate independently of bona fide gorilla telomeres. (A) G-rich LNA (left, in green) and C-rich PNA (right, in red) probes yield different telomere FISH profiles on the same gorilla metaphase. The C-rich PNA probe detects round and well-defined fluorescent signals, typical of telomeres. The G-rich LNA probe detects a much larger and not so well-defined area, which is associated with the heterochromatic caps. Contrary to the PRINS technique (29), the LNA probe does not detect paracentromeric telomere-like sequences present on particular gorilla chromosomes (29). Of note, extrachromosomal telomere signals are uniquely recognized by the C-rich probe (right). (B) The ReDFISH approach allows to examine the dynamics of replication of sequences revealed by PNA alone, LNA alone or both. The figure shows examples of extremities for which the detargeting occurred either simultaneously (yellow arrowhead), specifically for the LNA probe (green arrowhead) or specifically for the PNA probe (red arrowhead). (C) The percentage of LNA-revealed and PNA-revealed telomere sequences that replicated at different moments, thus suggesting distinct replication timings, is higher than that of sequences replicating together. (D) The replication of LNA-revealed (presumably subtelomeric) telomere sequences peaks significantly earlier than that of PNA-revealed (bona fide) telomere sequences (Fisher exact test), suggesting that the former follow a different replication program. Mean replication timings are indicated for both structures.
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gkt169-F2: Large telomere-like sequences detected by LNA telomeric probes replicate independently of bona fide gorilla telomeres. (A) G-rich LNA (left, in green) and C-rich PNA (right, in red) probes yield different telomere FISH profiles on the same gorilla metaphase. The C-rich PNA probe detects round and well-defined fluorescent signals, typical of telomeres. The G-rich LNA probe detects a much larger and not so well-defined area, which is associated with the heterochromatic caps. Contrary to the PRINS technique (29), the LNA probe does not detect paracentromeric telomere-like sequences present on particular gorilla chromosomes (29). Of note, extrachromosomal telomere signals are uniquely recognized by the C-rich probe (right). (B) The ReDFISH approach allows to examine the dynamics of replication of sequences revealed by PNA alone, LNA alone or both. The figure shows examples of extremities for which the detargeting occurred either simultaneously (yellow arrowhead), specifically for the LNA probe (green arrowhead) or specifically for the PNA probe (red arrowhead). (C) The percentage of LNA-revealed and PNA-revealed telomere sequences that replicated at different moments, thus suggesting distinct replication timings, is higher than that of sequences replicating together. (D) The replication of LNA-revealed (presumably subtelomeric) telomere sequences peaks significantly earlier than that of PNA-revealed (bona fide) telomere sequences (Fisher exact test), suggesting that the former follow a different replication program. Mean replication timings are indicated for both structures.

Mentions: In preliminary experiments for the application of the ReDFISH technique to gorilla chromosomes, we noticed that, contrary to chimpanzee chromosomes, telomere G-rich LNA and C-rich PNA probes gave different patterns of telomere hybridization on the same metaphases (Figure 2A). Although the C-rich PNA probe showed the usual pattern (well-circumscribed round fluorescent signals at nearly all chromosome extremities), the G-rich LNA probe revealed much larger, stronger and less well-delimited signals closely associated with the heterochromatic caps, suggesting that sequences containing large amounts of telomere or telomere-like repeats were present at this level. CO-FISH experiments indicated that telomere sequences giving rise to LNA signals were always on different sister chromatids from telomere sequences revealed by the PNA probe, indicating that they had the same orientation than bona fide telomeres (Figure 2B and Supplementary Figure S2). Such large telomere signals associated with gorilla chromosome ends have already been detected by others using both oligonucleotide probes and the PRINS technique (29). However, our G-rich LNA probe did not detect the large paracentromeric signals detected by PRINS on gorilla chromosomes 17 and 18 (29). This observation suggests that, unlike in the case of chimpanzee chromosome 17, the interstitial sequences in the gorilla complement carry largely degenerated telomeric repeats not efficiently recognized by the LNA probe.Figure 2.


The heterochromatic chromosome caps in great apes impact telomere metabolism.

Novo C, Arnoult N, Bordes WY, Castro-Vega L, Gibaud A, Dutrillaux B, Bacchetti S, Londoño-Vallejo A - Nucleic Acids Res. (2013)

Large telomere-like sequences detected by LNA telomeric probes replicate independently of bona fide gorilla telomeres. (A) G-rich LNA (left, in green) and C-rich PNA (right, in red) probes yield different telomere FISH profiles on the same gorilla metaphase. The C-rich PNA probe detects round and well-defined fluorescent signals, typical of telomeres. The G-rich LNA probe detects a much larger and not so well-defined area, which is associated with the heterochromatic caps. Contrary to the PRINS technique (29), the LNA probe does not detect paracentromeric telomere-like sequences present on particular gorilla chromosomes (29). Of note, extrachromosomal telomere signals are uniquely recognized by the C-rich probe (right). (B) The ReDFISH approach allows to examine the dynamics of replication of sequences revealed by PNA alone, LNA alone or both. The figure shows examples of extremities for which the detargeting occurred either simultaneously (yellow arrowhead), specifically for the LNA probe (green arrowhead) or specifically for the PNA probe (red arrowhead). (C) The percentage of LNA-revealed and PNA-revealed telomere sequences that replicated at different moments, thus suggesting distinct replication timings, is higher than that of sequences replicating together. (D) The replication of LNA-revealed (presumably subtelomeric) telomere sequences peaks significantly earlier than that of PNA-revealed (bona fide) telomere sequences (Fisher exact test), suggesting that the former follow a different replication program. Mean replication timings are indicated for both structures.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3643582&req=5

gkt169-F2: Large telomere-like sequences detected by LNA telomeric probes replicate independently of bona fide gorilla telomeres. (A) G-rich LNA (left, in green) and C-rich PNA (right, in red) probes yield different telomere FISH profiles on the same gorilla metaphase. The C-rich PNA probe detects round and well-defined fluorescent signals, typical of telomeres. The G-rich LNA probe detects a much larger and not so well-defined area, which is associated with the heterochromatic caps. Contrary to the PRINS technique (29), the LNA probe does not detect paracentromeric telomere-like sequences present on particular gorilla chromosomes (29). Of note, extrachromosomal telomere signals are uniquely recognized by the C-rich probe (right). (B) The ReDFISH approach allows to examine the dynamics of replication of sequences revealed by PNA alone, LNA alone or both. The figure shows examples of extremities for which the detargeting occurred either simultaneously (yellow arrowhead), specifically for the LNA probe (green arrowhead) or specifically for the PNA probe (red arrowhead). (C) The percentage of LNA-revealed and PNA-revealed telomere sequences that replicated at different moments, thus suggesting distinct replication timings, is higher than that of sequences replicating together. (D) The replication of LNA-revealed (presumably subtelomeric) telomere sequences peaks significantly earlier than that of PNA-revealed (bona fide) telomere sequences (Fisher exact test), suggesting that the former follow a different replication program. Mean replication timings are indicated for both structures.
Mentions: In preliminary experiments for the application of the ReDFISH technique to gorilla chromosomes, we noticed that, contrary to chimpanzee chromosomes, telomere G-rich LNA and C-rich PNA probes gave different patterns of telomere hybridization on the same metaphases (Figure 2A). Although the C-rich PNA probe showed the usual pattern (well-circumscribed round fluorescent signals at nearly all chromosome extremities), the G-rich LNA probe revealed much larger, stronger and less well-delimited signals closely associated with the heterochromatic caps, suggesting that sequences containing large amounts of telomere or telomere-like repeats were present at this level. CO-FISH experiments indicated that telomere sequences giving rise to LNA signals were always on different sister chromatids from telomere sequences revealed by the PNA probe, indicating that they had the same orientation than bona fide telomeres (Figure 2B and Supplementary Figure S2). Such large telomere signals associated with gorilla chromosome ends have already been detected by others using both oligonucleotide probes and the PRINS technique (29). However, our G-rich LNA probe did not detect the large paracentromeric signals detected by PRINS on gorilla chromosomes 17 and 18 (29). This observation suggests that, unlike in the case of chimpanzee chromosome 17, the interstitial sequences in the gorilla complement carry largely degenerated telomeric repeats not efficiently recognized by the LNA probe.Figure 2.

Bottom Line: In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species.Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution.In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres.

View Article: PubMed Central - PubMed

Affiliation: Telomeres and Cancer laboratory, 'Equipe Labellisée Ligue contre le Cancer', UMR3244, Institut Curie, 26 rue d'Ulm, 75248 Paris, France.

ABSTRACT
In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species. Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution. Here, we show that telomeres on chromosome arms carrying subtelomeric heterochromatic caps in the chimpanzee, which are completely absent in humans, replicate later than telomeres on chromosome arms without caps. In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres. Strikingly, telomere-containing RNA accumulates extrachromosomally in gorilla mitotic cells, suggesting that at least some aspects of telomere-containing RNA biogenesis have diverged in gorilla, perhaps in concert with the evolution of heterochromatic caps in this species.

Show MeSH
Related in: MedlinePlus