Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes
- 1University of California, Santa Barbara
Abstract
CpG dinucleotides are essential substrates for DNA methylation and genome regulation, yet paradoxically, methylated CpGs are lost through deamination-associated mutations. How CpG-rich sequences persist and are replenished during evolution remains unresolved, as previous sequencing technologies left structurally complex regions inaccessible. Here, leveraging complete telomere-to-telomere ape genomes, we show that peri/centromeric satellites are reservoirs of hypomethylated CpGs in sperm, and likely oocytes. This peri/centromeric hypomethylation extends into adjacent euchromatin, revealing novel centromeric hypomethylation extension domains enriched for segmental duplications, recently duplicated genes, and testis- and brain-biased expression. More broadly, young structural variants are CpG-rich and germline-hypomethylated, whereas older sequences are methylated and CpG-depleted. These findings link rapidly evolving centromeric regions to distinctive germline epigenetic state, CpG evolution, and structural and transcriptomic evolutionary innovation.
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BibTeX
@misc{son2026germline,
title = {{Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes}},
author = {D. R. Son and E. Y.- H. Loh and H. Jeong and J. Ma and E. E. Eichler and S. V. Yi},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.15.732472},
url = {https://www.biorxiv.org/content/10.64898/2026.06.15.732472v3},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes
AU - D. R. Son
AU - E. Y.- H. Loh
AU - H. Jeong
AU - J. Ma
AU - E. E. Eichler
AU - S. V. Yi
PY - 2026
DA - 2026/06/15
PB - bioRxiv
DO - 10.64898/2026.06.15.732472
UR - https://www.biorxiv.org/content/10.64898/2026.06.15.732472v3
AB - CpG dinucleotides are essential substrates for DNA methylation and genome regulation, yet paradoxically, methylated CpGs are lost through deamination-associated mutations. How CpG-rich sequences persist and are replenished during evolution remains unresolved, as previous sequencing technologies left structurally complex regions inaccessible. Here, leveraging complete telomere-to-telomere ape genomes, we show that peri/centromeric satellites are reservoirs of hypomethylated CpGs in sperm, and likely oocytes. This peri/centromeric hypomethylation extends into adjacent euchromatin, revealing novel centromeric hypomethylation extension domains enriched for segmental duplications, recently duplicated genes, and testis- and brain-biased expression. More broadly, young structural variants are CpG-rich and germline-hypomethylated, whereas older sequences are methylated and CpG-depleted. These findings link rapidly evolving centromeric regions to distinctive germline epigenetic state, CpG evolution, and structural and transcriptomic evolutionary innovation.
ER -