Limits...
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.

Show MeSH

Related in: MedlinePlus

Chimpanzee telomeres associated with heterochromatic caps replicate late. (A) Single telomeres in chimpanzee tend to replicate at particular moments of the S-phase. Single telomere replication was analyzed using ReDFISH as previously described (11). Briefly, synchronized cells were released in S-phase, and different batches were BrdU pulse-labeled for 1 h at different times. Metaphasic chromosomes were prepared and treated so that telomeres that had replicated during the pulse will be rendered single stranded and revealed by only one telomere probe (either G- or C-rich). The histogram represents the percentage of replicating telomeres for every chromosome arm detected during early S, middle S and late S pulses in horizontal bars. The total sum of partial percentages is normalized to 100%. An asterisk marks the extremities that bear a heterochromatic cap. Bar errors (α = 0.05) are indicated only for the mid-S percentages for simplification. (B) Total absence of correlation between the mean replication timing of chimpanzee extremities (as determined in this article), regardless of whether they bear a heterochromatic cap (orange and green squares, respectively), and that of the homologous human chromosome extremities [as determined previously (11)] (Supplementary Table S1). Correlation coefficients and P-values (Spearman correlation test) are indicated on top of the scatter plot. (C) The mean replication time of chimpanzee extremities bearing heterochromatic caps is significantly higher than that of extremities without caps.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3643582&req=5

gkt169-F1: Chimpanzee telomeres associated with heterochromatic caps replicate late. (A) Single telomeres in chimpanzee tend to replicate at particular moments of the S-phase. Single telomere replication was analyzed using ReDFISH as previously described (11). Briefly, synchronized cells were released in S-phase, and different batches were BrdU pulse-labeled for 1 h at different times. Metaphasic chromosomes were prepared and treated so that telomeres that had replicated during the pulse will be rendered single stranded and revealed by only one telomere probe (either G- or C-rich). The histogram represents the percentage of replicating telomeres for every chromosome arm detected during early S, middle S and late S pulses in horizontal bars. The total sum of partial percentages is normalized to 100%. An asterisk marks the extremities that bear a heterochromatic cap. Bar errors (α = 0.05) are indicated only for the mid-S percentages for simplification. (B) Total absence of correlation between the mean replication timing of chimpanzee extremities (as determined in this article), regardless of whether they bear a heterochromatic cap (orange and green squares, respectively), and that of the homologous human chromosome extremities [as determined previously (11)] (Supplementary Table S1). Correlation coefficients and P-values (Spearman correlation test) are indicated on top of the scatter plot. (C) The mean replication time of chimpanzee extremities bearing heterochromatic caps is significantly higher than that of extremities without caps.

Mentions: We next determined the timing of replication of individual telomeres in chimpanzee primary fibroblasts. We found that, similarly to humans (11), chimpanzee telomeres replicate all along the S-phase with a trend for specific chromosome extremities to replicate at particular moments (Figure 1A). To test whether the timing of replication for individual chromosomes was similar to the human replication pattern, we compared the mean replication scores calculated for each telomere in chimpanzee (Supplementary Table S1) to the mean replication scores calculated for the homologous extremities in the human fibroblast IMR90 [as determined in a previous study (11)]. As shown in Figure 1B, there is no significant correlation between the telomere-specific replication timing of these species, regardless of whether these extremities carried heterochromatic caps as in the chimpanzee. Interestingly, telomeres associated with chromosome extremities that carry heterochromatic caps seemed to replicate later than the others in the chimpanzee (Figure 1A and B). In fact, the mean replication timings of chimpanzee cap-associated telomeres are significantly higher than that of non-cap–associated telomeres in the same species (unpaired t-test: P < 0.0001) (Figure 1C). Therefore, although the order of replication of individual telomeres differs between human and chimpanzee, a late replication dynamics seems to be associated with the presence of heterochromatinization domains in the subtelomere in both species (11).Figure 1.


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)

Chimpanzee telomeres associated with heterochromatic caps replicate late. (A) Single telomeres in chimpanzee tend to replicate at particular moments of the S-phase. Single telomere replication was analyzed using ReDFISH as previously described (11). Briefly, synchronized cells were released in S-phase, and different batches were BrdU pulse-labeled for 1 h at different times. Metaphasic chromosomes were prepared and treated so that telomeres that had replicated during the pulse will be rendered single stranded and revealed by only one telomere probe (either G- or C-rich). The histogram represents the percentage of replicating telomeres for every chromosome arm detected during early S, middle S and late S pulses in horizontal bars. The total sum of partial percentages is normalized to 100%. An asterisk marks the extremities that bear a heterochromatic cap. Bar errors (α = 0.05) are indicated only for the mid-S percentages for simplification. (B) Total absence of correlation between the mean replication timing of chimpanzee extremities (as determined in this article), regardless of whether they bear a heterochromatic cap (orange and green squares, respectively), and that of the homologous human chromosome extremities [as determined previously (11)] (Supplementary Table S1). Correlation coefficients and P-values (Spearman correlation test) are indicated on top of the scatter plot. (C) The mean replication time of chimpanzee extremities bearing heterochromatic caps is significantly higher than that of extremities without caps.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkt169-F1: Chimpanzee telomeres associated with heterochromatic caps replicate late. (A) Single telomeres in chimpanzee tend to replicate at particular moments of the S-phase. Single telomere replication was analyzed using ReDFISH as previously described (11). Briefly, synchronized cells were released in S-phase, and different batches were BrdU pulse-labeled for 1 h at different times. Metaphasic chromosomes were prepared and treated so that telomeres that had replicated during the pulse will be rendered single stranded and revealed by only one telomere probe (either G- or C-rich). The histogram represents the percentage of replicating telomeres for every chromosome arm detected during early S, middle S and late S pulses in horizontal bars. The total sum of partial percentages is normalized to 100%. An asterisk marks the extremities that bear a heterochromatic cap. Bar errors (α = 0.05) are indicated only for the mid-S percentages for simplification. (B) Total absence of correlation between the mean replication timing of chimpanzee extremities (as determined in this article), regardless of whether they bear a heterochromatic cap (orange and green squares, respectively), and that of the homologous human chromosome extremities [as determined previously (11)] (Supplementary Table S1). Correlation coefficients and P-values (Spearman correlation test) are indicated on top of the scatter plot. (C) The mean replication time of chimpanzee extremities bearing heterochromatic caps is significantly higher than that of extremities without caps.
Mentions: We next determined the timing of replication of individual telomeres in chimpanzee primary fibroblasts. We found that, similarly to humans (11), chimpanzee telomeres replicate all along the S-phase with a trend for specific chromosome extremities to replicate at particular moments (Figure 1A). To test whether the timing of replication for individual chromosomes was similar to the human replication pattern, we compared the mean replication scores calculated for each telomere in chimpanzee (Supplementary Table S1) to the mean replication scores calculated for the homologous extremities in the human fibroblast IMR90 [as determined in a previous study (11)]. As shown in Figure 1B, there is no significant correlation between the telomere-specific replication timing of these species, regardless of whether these extremities carried heterochromatic caps as in the chimpanzee. Interestingly, telomeres associated with chromosome extremities that carry heterochromatic caps seemed to replicate later than the others in the chimpanzee (Figure 1A and B). In fact, the mean replication timings of chimpanzee cap-associated telomeres are significantly higher than that of non-cap–associated telomeres in the same species (unpaired t-test: P < 0.0001) (Figure 1C). Therefore, although the order of replication of individual telomeres differs between human and chimpanzee, a late replication dynamics seems to be associated with the presence of heterochromatinization domains in the subtelomere in both species (11).Figure 1.

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