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Reply to: Identification of old coding regions disproves the hominoid de novo status of genes

Nature Ecology & Evolution volume 8, pages 1831–1834 (2024)Cite this article

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The Original Article was published on 26 August 2024

replying to: E. Leushkin & H. Kaessmann Nature Ecology & Evolution https://doi.org/10.1038/s41559-024-02513-6 (2024)

We acknowledge the commentary by Leushkin and Kaessmann1 on our work2. While we are in agreement on the evolving nature of defining de novo genes with ribosome profiles, we respectfully disagree with their assertions regarding the definition of ages, de novo status, translation and functions of these genes. Notably, the common definition of de novo genes in the field is based on the age of the open reading frames (ORFs), rather than that of the loci3,4,5,6. Moreover, although ribosome profiles are indicative of translation, the profiles derived from a limited range of temporospatial conditions do not necessarily establish a ground truth for the robust translation and functions of de novo genes. Here we present additional data and analyses to counter their assertions, particularly verifying the status of these new genes and providing compelling evidence for in vivo translation of the case gene. The data presented here, together with those from our initial report, clearly verify our original conclusions.

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Fig. 1: ENSG00000205704 encodes a hominoid-specific de novo protein.

Data availability

The mass spectrometry data from this study have been deposited to PRIDE24 with the dataset identifier PXD053929. Public Ribo-seq datasets re-analysed in this study are summarized in Supplementary Table 1 (for ENSG00000205704) and http://test.rhesusbase.com/denovo (for the 74 de novo genes from An et al.2). Ribosome profiles derived from GWIPS-viz (https://gwips.ucc.ie/cgi-bin/hgTracks?db=hg38) were integrated from sub-tracks, including Clamer 2018, Fijalkowska 2017, Gao 2014 and Gawron 2016.

Code availability

The codes and pipelines from this study have been published previously and are cited in the Supplementary Methods. Multiple sequence alignments were extracted from https://hgdownload.soe.ucsc.edu/downloads.html.

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Author information

Authors and Affiliations

  1. State Key Laboratory of Protein and Plant Gene Research, Laboratory of Bioinformatics and Genomic Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China

    Chunfu Xiao, Chao Yao, Ting Li, Xiaoge Liu, Ni A. An & Chuan-Yun Li

  2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Fan Mo, Yingfei Lu, Jianhuan Qi & Baoyang Hu

  3. University of Chinese Academy of Sciences, Beijing, China

    Fan Mo, Yingfei Lu, Jianhuan Qi & Baoyang Hu

  4. Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China

    Qi Xiao & Tiannan Guo

  5. School of Medicine, School of Life Sciences, Westlake University, Hangzhou, China

    Qi Xiao & Tiannan Guo

  6. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China

    Jia-Yu Chen

  7. Chinese Institute for Brain Research, Beijing, China

    Li Zhang & Chuan-Yun Li

  8. Southwest United Graduate School, Kunming, China

    Chuan-Yun Li

Authors
  1. Chunfu Xiao
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  2. Fan Mo
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  10. Li Zhang
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  13. Ni A. An
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  14. Chuan-Yun Li
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Contributions

C.-Y.L., B.H. and N.A.A. designed the study. C.X. performed most of the computational analyses. Q.X., C.Y., T.L., J.-Y.C. and L.Z. performed part of the analyses. F.M., Y.L., Q.X., J.Q., X.L. and T.G. performed the experiments. C.-Y.L., C.X., N.A.A. and B.H. wrote the paper. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Baoyang Hu, Ni A. An or Chuan-Yun Li.

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The authors declare no competing interests.

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Nature Ecology & Evolution thanks Sebastiaan van Heesch and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1 and 2 and Table 1.

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Xiao, C., Mo, F., Lu, Y. et al. Reply to: Identification of old coding regions disproves the hominoid de novo status of genes. Nat Ecol Evol 8, 1831–1834 (2024). https://doi.org/10.1038/s41559-024-02515-4

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