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The genomic landscape of evolutionary convergence in mammals, birds and reptiles

Nature Ecology & Evolution volume 1, Article number: 0041 (2017) Cite this article

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Abstract

Many lineage-defining (nodal) mutations possess high functionality. However, differentiating adaptive nodal mutations from those that are functionally compensated remains challenging. To address this challenge, we identified functional nodal mutations (fNMs) in ~3,400 nuclear DNA (nDNA) and 4 mitochondrial DNA (mtDNA) protein structures from 91 and 1,003 species, respectively, representing the entire mammalian, bird and reptile phylogeny. A screen for candidate compensatory mutations among co-occurring amino acid changes in close structural proximity revealed that such compensated fNMs encompass 37% and 27% of the mtDNA and nDNA datasets, respectively. Analysis of the remaining (non-compensated) mutations, which are enriched for adaptive mutations, showed that birds and mammals share most such recurrent fNMs (N = 51). Among the latter, we discovered mutations in thermoregulation-related genes. These represent the best candidates to explain the molecular basis of convergent body thermoregulation in birds and mammals. Our analysis reveals the landscape of possible mutational compensation and convergence in amniote phylogeny.

Positive selection for functional mutations constitutes one of the principal mechanisms underlying the emergence of evolutionary novelties and adaptation to new environments. However, since conservation of biological functions is generally favoured, most mutations with high functional potential have either been removed by negative selection, or survived because of intra- or intergenic (that is, epistatic) compensation1. Furthermore, when explaining the long-term survival of high-functional-score ancient mutations that define lineages or species (with five or more branches) in phylo­genetic trees (that is, nodal mutations)2, two alternative mechanisms predominate: positive selection or mutational compensation. Compensation of functional mutations (co-occurrence with additional mutations that ‘compromise’ their function) acts to retain biological function, and when this is interfered with, diseases may occur. An example of this is the differential penetrance of disease-causing and disease-associated mutations in different populations3. Similarly, it has been shown that certain human disease-causing mutations exist as common variants in other species, suggesting that the genomic context of these species enabled such mutations to survive, again because of compensations4–7.

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Figure 1: Illustration demonstrating fNM potential compensation and possible adaptation in a protein-coding gene.
Figure 2: Prevalence assessment of potential compensation for fNMs in amniotes.
Figure 3: Analysis of shared non-compensated fRNMs between all possible tree branches.

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Acknowledgements

We thank R. Zarivach for critical discussions and the Negev Foundation for a Scholarship of Excellence awarded to L.L. This study was funded by research grants from the Israeli Science Foundation (610/12), Binational Science Foundation and a US Army Life Science division grant 67993LS awarded to D.M.

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Authors and Affiliations

  1. Department of Life Sciences, Building 40, Room 009, Ben Gurion University of the Negev, Beer-Sheva, Israel 8410501

    Liron Levin & Dan Mishmar

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  1. Liron Levin
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Correspondence to Dan Mishmar.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures 1–5; supplementary Tables 1–4 (PDF 1434 kb)

Supplementary Dataset 1

Nodal mutations identified in mtDNA tRNAs genes, mtDNA rRNAs genes and nodal mutations identified in mtDNA protein coding genes. (XLSX 3372 kb)

Supplementary Dataset 2

Nodal mutations identified in nDNA-encoded protein genes. (XLSX 16633 kb)

Supplementary Dataset 3

MATLAB scripts generated for the analysis presented in this Article. (ZIP 3831 kb)

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Levin, L., Mishmar, D. The genomic landscape of evolutionary convergence in mammals, birds and reptiles. Nat Ecol Evol 1, 0041 (2017). https://doi.org/10.1038/s41559-016-0041

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