Surveying the sequence diversity of model prebiotic peptides by mass spectrometry
Jay G. Forsythea,1, Anton S. Petrova, W. Calvin Millarb,2, Sheng-Sheng Yuc, Ramanarayanan Krishnamurthyd, Martha A. Groverc, Nicholas V. Huda, and Facundo M. Fernándeza,3
Author Affiliations
aSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400;
bSchool of Physics, Georgia Institute of Technology, Atlanta, GA 30332-0430;
cSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100;
dDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
Edited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved August 7, 2017 (received for review June 29, 2017)
Significance
Peptides and proteins are essential for life as we know it, and likely played a critical role in the origins of life as well. In recent years, much progress has been made in understanding plausible routes from amino acids to peptides. However, little is known about the diversity of sequences that could have been produced by abiotic condensation reactions on the prebiotic earth. In this study, multidimensional separations were coupled with mass spectrometry to detect and sequence mixtures of model proto-peptides. It was observed that, starting with a few monomers, proto-peptide diversity increased rapidly following cycling. Experimental proto-peptide sequences were compared with theoretically random sequences, revealing a high sequence diversity of plausible monomer combinations.
Abstract
The rise of peptides with secondary structures and functions would have been a key step in the chemical evolution which led to life. As with modern biology, amino acid sequence would have been a primary determinant of peptide structure and activity in an origins-of-life scenario. It is a commonly held hypothesis that unique functional sequences would have emerged from a diverse soup of proto-peptides, yet there is a lack of experimental data in support of this. Whereas the majority of studies in the field focus on peptides containing only one or two types of amino acids, here we used modern mass spectrometry (MS)-based techniques to separate and sequence de novo proto-peptides containing broader combinations of prebiotically plausible monomers. Using a dry–wet environmental cycling protocol, hundreds of proto-peptide sequences were formed over a mere 4 d of reaction. Sequence homology diagrams were constructed to compare experimental and theoretical sequence spaces of tetrameric proto-peptides. MS-based analyses such as this will be increasingly necessary as origins-of-life researchers move toward systems-level investigations of prebiotic chemistry.
prebiotic chemistry chemical evolution peptides mass spectrometry depsipeptides
Footnotes
1Present address: Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424.
2Present address: Master’s Industrial Internship Program, University of Oregon, Eugene, OR 97403.
3To whom correspondence should be addressed. Email: facundo.fernandez@chemistry.gatech.edu.
Author contributions: J.G.F., A.S.P., R.K., M.A.G., N.V.H., and F.M.F. designed research; J.G.F., A.S.P., W.C.M., and S.-S.Y. performed research; J.G.F., R.K., M.A.G., N.V.H., and F.M.F. analyzed data; and J.G.F. and F.M.F. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: All depsipeptide sequences reported in this paper can be accessed in Dataset S1.
This article contains supporting information online at
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