Genetic studies of human–chimpanzee divergence using stem cell fusions


Comparative studies of humans and chimpanzees have revealed many anatomical, physiological, behavioral, and molecular differences. However, it has been challenging to map these differences to particular chromosome regions. Here, we develop a genetic approach in fused stem cell lines that makes it possible to map human–chimpanzee molecular and cellular differences to specific regions of the genome. We illustrate this approach by mapping chromosome regions responsible for species-specific gene expression differences in fused tetraploid cells. This approach is general, and could be used in the future to map the genomic changes that control many other human–chimpanzee differences in various cell types or organoids in vitro. Data supporting the findings of this study are included in the main text and [ SI Appendix ][1] or deposited in publicly available databases. RNAseq data generated in this study are available at Gene Expression Omnibus ([GSE184768][2]) ([58][3]), and the DNA sequence containing the recombination site for H1C1a-X1-Xrec1 is available at GenBank ([OK283040][4]) ([59][5]). Additional materials will be made available upon request. [1]: https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2117557118/-/DCSupplemental [2]: /lookup/external-ref?link_type=NCBIGEO&access_num=GSE184768&atom=%2Fpnas%2F118%2F51%2Fe2117557118.atom [3]: #ref-58 [4]: /lookup/external-ref?link_type=GEN&access_num=OK283040&atom=%2Fpnas%2F118%2F51%2Fe2117557118.atom [5]: #ref-59

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