Probing the genomic limits of de-extinction in the Christmas Island rat
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Three principal methods are under discussion as possible pathways to “true” de-extinction; i.e., back-breeding, cloning, and genetic engineering.1,2 Of these, while the latter approach is most likely to apply to the largest number of extinct species, its potential is constrained by the degree to which the extinct species genome can be reconstructed. We explore this question using the extinct Christmas Island rat (Rattus macleari) as a model, an endemic rat species that was driven extinct between 1898 and 1908.3–5 We first re-sequenced its genome to an average of >60× coverage, then mapped it to the reference genomes of different Rattus species. We then explored how evolutionary divergence from the extant reference genome affected the fraction of the Christmas Island rat genome that could be recovered. Our analyses show that even when the extremely high-quality Norway brown rat (R. norvegicus) is used as a reference, nearly 5% of the genome sequence is unrecoverable, with 1,661 genes recovered at lower than 90% completeness, and 26 completely absent. Furthermore, we find the distribution of regions affected is not random, but for example, if 90% completeness is used as the cutoff, genes related to immune response and olfaction are excessively affected. Ultimately, our approach demonstrates the importance of applying similar analyses to candidates for de-extinction through genome editing in order to provide critical baseline information about how representative the edited form would be of the extinct species.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Current Biology |
| Vol/bind | 32 |
| Udgave nummer | 7 |
| Sider (fra-til) | 1650-1656.e3 |
| ISSN | 0960-9822 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors acknowledge the Oxford University Museum of Natural History for originally providing the loan of the materials to ADG, and Mikkel-Holger Strander Sinding for ongoing discussion about the potential and challenges of de-extinction. We also acknowledge ERC Consolidator Award 681396 ?Extinction Genomics,? Danish National Research Foundation Award DNRF143, Program of Study Abroad for Postdoctoral Researcher of College of Life Sciences, ZJU, and Scientific Research Foundation for Talents, STU (NTF21026) for funding this research. Designed the study: M.T.P.G. Generated palaeogenomic data: C.C. O.S. and M.M.C. Analyzed data: J.L. D.D. J.N. and D.R. Provided additional computational and laboratory guidance/support: S.G. and G.Z. Provided samples and context: A.D.G. and R.M. Provided modern reference datasets and wrote the paper: J.L. and M.T.P.G. with input from all other authors. M.T.P.G. is on the advisory board of Current Biology.
Funding Information:
The authors acknowledge the Oxford University Museum of Natural History for originally providing the loan of the materials to ADG, and Mikkel-Holger Strander Sinding for ongoing discussion about the potential and challenges of de-extinction. We also acknowledge ERC Consolidator Award 681396 “Extinction Genomics,” Danish National Research Foundation Award DNRF143 , Program of Study Abroad for Postdoctoral Researcher of College of Life Sciences , ZJU , and Scientific Research Foundation for Talents , STU ( NTF21026 ) for funding this research.
Publisher Copyright:
© 2022 The Author(s)
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