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Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth

Nature Ecology & Evolution volume 1, Article number: 0146 (2017) Cite this article

Subjects

Abstract

The phenomenon of de novo gene birth from junk DNA is surprising, because random polypeptides are expected to be toxic. There are two conflicting views about how de novo gene birth is nevertheless possible: the continuum hypothesis invokes a gradual gene birth process, whereas the preadaptation hypothesis predicts that young genes will show extreme levels of gene-like traits. We show that intrinsic structural disorder conforms to the predictions of the preadaptation hypothesis and falsifies the continuum hypothesis, with all genes having higher levels than translated junk DNA, but young genes having the highest level of all. Results are robust to homology detection bias, to the non-independence of multiple members of the same gene family and to the false positive annotation of protein-coding genes.

It has become clear that protein-coding genes can originate de novo from non-coding sequences1. This is surprising, because amyloid is a generic structural form of any polypeptide, making the expression of random polypeptides a dangerous affair2. De novo gene birth is a radical evolutionary transition, and two hypotheses have previously been presented to explain how it is possible. The ‘continuum’ view posits that there is a series of intermediate stages, or ‘proto-genes’, between non-genes and genes3. In contrast, the ‘preadaptation’ theory posits that de novo birth is an all-or-nothing transition to functionality, and the key to successful innovation is the imperative to avoid the most toxic ‘hopeless monster’ options in favour of ‘hopeful monsters’4–6; given a marker for such avoidance, newborn genes will therefore have exaggerated, rather than intermediate, gene-like characteristics. In other words, newborn gene birth occurs only from sequences that happen to be pre-adapted to ‘first, do no harm’ in the most direct way possible. Only later do they adapt to protect themselves against risks in subtler ways, increasing tolerance with respect to other more subtle characteristics7.

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Figure 1
Figure 2: Young genes have higher ISD (black circles) than old genes.
Figure 3: In agreement with many previous studies, young genes evolve faster and are shorter.
Figure 4: Elevated ISD can be broken down into contributions from amino acid composition and from exact amino acid order.
Figure 5: Putative evidence for the continuum hypothesis can be explained as a statistical artefact known as Simpson’s paradox.
Figure 6: Young yeast genes, like the young mouse genes in Fig. 2, have higher ISD.

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Acknowledgements

Work was supported by the John Templeton Foundation (39667), the National Institutes of Health (GM104040) and ERC grant NewGenes (322564). We thank D. Tautz and M. Cordes for discussions, R. Bakaric for assistance with phylostratigraphy and A.-R. Carvunis for comments on a draft of the manuscript and for sharing data.

Author information

Author notes

  1. Scott G. Foy & Rafik Neme

    Present address: *Present addresses: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA (S.G.F.); Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York 10032, USA (R.N.).,

  2. Benjamin A. Wilson and Scott G. Foy: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, USA.

    Benjamin A. Wilson, Scott G. Foy & Joanna Masel

  2. Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, SH 24306, Germany.

    Rafik Neme

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Contributions

J.M and R.N. conceived the approach, R.N. performed the phylostratigraphy, B.A.W. and S.G.F. completed all other data analyses, and J.M. wrote the paper.

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Correspondence to Joanna Masel.

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Supplementary information

Supplementary information

Supplementary Figure 1 and Supplementary Table 1 (PDF 376 kb)

Supplementary Table 2

M. musculus proteins. (CSV 12497 kb)

Supplementary Table 3

Nucleotide sequences from intergenic regions of M. musculus genome (CSV 70010 kb)

Supplementary Table 4

Nucleotide sequences from intergenic regions of the masked M. musculus genome (CSV 70154 kb)

Supplementary Table 5

Randomly generated nucleotide sequences (CSV 35221 kb)

Supplementary Table 6

Scrambled amino acid sequences (CSV 12119 kb)

Supplementary Table 7

S. cerevisiae proteins from Table 1 (CSV 3330 kb)

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Wilson, B., Foy, S., Neme, R. et al. Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth. Nat Ecol Evol 1, 0146 (2017). https://doi.org/10.1038/s41559-017-0146

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