Incomplete lineage sorting of segmental duplications defines the human chromosome 2 fusion site early during African great ape speciation
All great apes differ karyotypically from humans due to the fusion of chromosomes 2a and 2b, resulting in human chromosome 2. Here, we show that the fusion was associated with multiple pericentric inversions, segmental duplications (SDs), and the turnover of subterminal repetitive DNA. We characterized the fusion site at the single-base-pair resolution and identified three distinct SDs that originated more than 5 million years ago. These three distinct SDs were differentially distributed among African great apes as a result of incomplete lineage sorting (ILS) and lineage-specific duplication. One of these SDs shares homology to a hypomethylated SD spacer sequence present in the subterminal heterochromatin of Pan but is completely absent subtelomerically in both humans and orangutans. CRISPR-Cas9-mediated depletion of the fusion site in human neural progenitor cells alters the expression of genes, indicating a potential regulatory consequence to this human-specific karyotypic change. Overall, this study offers insights into how complex regions subject to ILS may contribute to speciation.
Authors
- Kitty Jieyi Chen (ORCID: https://orcid.org/0000-0002-6505-198X)
- Evan E. Eichler (ORCID: https://orcid.org/0000-0002-8246-4014)
- Lu Zhang (ORCID: https://orcid.org/0000-0002-4858-0361)
- Guojie Zhang (ORCID: https://orcid.org/0000-0001-6860-1521)
- Yong‐Jie Lu (ORCID: https://orcid.org/0000-0001-6174-6621)
- Mario Ventura (ORCID: https://orcid.org/0000-0001-7762-8777)
- Zikun Yang (ORCID: https://orcid.org/0000-0002-8834-6377)
- Yafei Mao (ORCID: https://orcid.org/0000-0002-9648-4278)
- Xiangyu Yang (ORCID: https://orcid.org/0000-0003-1081-3657)
- DongAhn Yoo (ORCID: https://orcid.org/0000-0003-0033-3721)
- Xinyan Bian
- Kaiyue Ma (ORCID: https://orcid.org/0009-0001-4302-3371)
- Yanhong Nie
- Juan Zhang (ORCID: https://orcid.org/0000-0002-7338-7942)
- Shilong Zhang (ORCID: https://orcid.org/0009-0003-5796-2577)
- Xinrui Jiang (ORCID: https://orcid.org/0000-0002-0929-6667)
- Qiang Sun (ORCID: https://orcid.org/0000-0002-3359-9465)
- Lianting Fu
- Junmin Han
Institutions
- Howard Hughes Medical Institute (US)
- Shanghai Jiao Tong University (CN)
- University of Washington (US)
- University of Washington Medical Center (US)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Shanghai Institutes for Biological Sciences (CN)
- International Peace Maternity & Child Health Hospital (CN)
- Ministry of Education (ME)
- Zhejiang Hospital (CN)
- Women's Hospital, School of Medicine, Zhejiang University (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- University of Bari Aldo Moro (IT)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1016/j.xgen.2025.101079
- Citations
- 1
- Primary Topic
- Genomic variations and chromosomal abnormalities
- Type
- article
- Field-Weighted Citation Impact
- 1.82