Abstract
Recent findings, in vitro and in silico, are strengthening the idea of a simpler, earlier stage of genetically encoded proteins which used amino acids produced by prebiotic chemistry. These findings motivate a re-examination of prior work which has identified unusual properties of the set of twenty amino acids found within the full genetic code, while leaving it unclear whether similar patterns also characterize the subset of prebiotically plausible amino acids. We have suggested previously that this ambiguity may result from the low number of amino acids recognized by the definition of prebiotic plausibility used for the analysis. Here, we test this hypothesis using significantly updated data for organic material detected within meteorites, which contain several coded and non-coded amino acids absent from prior studies. In addition to confirming the well-established idea that “late” arriving amino acids expanded the chemistry space encoded by genetic material, we find that a prebiotically plausible subset of coded amino acids generally emulates the patterns found in the full set of 20, namely an exceptionally broad and even distribution of volumes and an exceptionally even distribution of hydrophobicities (quantified as logP) over a narrow range. However, the strength of this pattern varies depending on both the size and composition the library used to create a background (null model) for a random alphabet, and the precise definition of exactly which amino acids were present in a simpler, earlier code. Findings support the idea that a small sample size of amino acids caused previous ambiguous results, and further improvements in meteorite analysis, and/or prebiotic simulations will further clarify the nature and extent of unusual properties. We discuss the case of sulfur-containing amino acids as a specific and clear example and conclude by reviewing the potential impact of better understanding the chemical “logic” of a smaller forerunner to the standard amino acid alphabet.
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adapted from Mayer-Bacon and Freeland (2021) A Percentage of random amino acid alphabets exhibiting broader range, more even distribution within that range, or both (relative to a set of coded amino acids), in descriptors for molecular volume and hydrophobicity. B: Percentage of random amino acid alphabets exhibiting both better range and more even distribution than a set of coded amino acids for either volume, hydrophobicity, or both. In A and B, numbers in white text on a black background are for random sets of 8 meteoritic α-amino acids (from a library of 44 α-amino acids) compared to 8 coded amino acids identified in meteorites. Numbers in black text are for random sets of 20 (from a library of 1949) compared to the full genetically coded amino acid alphabet
adapted from Mayer-Bacon and Freeland (2021) (Color figure online)
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Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223. https://doi.org/10.1126/science.181.4096.223
Aponte JC, Elsila JE, Hein JE et al (2020) Analysis of amino acids, hydroxy acids, and amines in CR chondrites. Meteorit Planet Sci 55:2422–2439. https://doi.org/10.1111/maps.13586
Benner SA, Ellington AD, Tauer A (1989) Modern metabolism as a palimpsest of the RNA world. Proc Natl Acad Sci 86:7054–7058. https://doi.org/10.1073/pnas.86.18.7054
Blanco C, Bayas M, Yan F, Chen IA (2018) Analysis of evolutionarily independent protein-RNA complexes yields a criterion to evaluate the relevance of prebiotic scenarios. Curr Biol 28:526-537.e5. https://doi.org/10.1016/j.cub.2018.01.014
Cheng RP, Gellman SH, DeGrado WF (2001) β-peptides: from structure to function. Chem Rev 101:3219–3232. https://doi.org/10.1021/cr000045i
Chiesl TN, Chu WK, Stockton AM et al (2009) Enhanced amine and amino acid analysis using pacific blue and the mars organic analyzer microchip capillary electrophoresis system. Anal Chem 81:2537–2544. https://doi.org/10.1021/ac8023334
Cleaves HJ (2010) The origin of the biologically coded amino acids. J Theor Biol 263:490–498. https://doi.org/10.1016/j.jtbi.2009.12.014
Cooper G, Kimmich N, Belisle W et al (2001) Carbonaceous meteorites as a source of sugar-related organic compounds for the early earth. Nature 414:879–883. https://doi.org/10.1038/414879a
Despotović D, Longo LM, Aharon E et al (2020) Polyamines mediate folding of primordial hyperacidic helical proteins. Biochemistry 59:4456–4462. https://doi.org/10.1021/acs.biochem.0c00800
Elsila JE, Aponte JC, Blackmond DG et al (2016) Meteoritic amino acids: diversity in compositions reflects parent body histories. ACS Cent Sci 2:370–379. https://doi.org/10.1021/acscentsci.6b00074
Feldman AW, Dien VT, Karadeema RJ et al (2019) Optimization of replication, transcription, and translation in a semi-synthetic organism. J Am Chem Soc 141:10644–10653. https://doi.org/10.1021/jacs.9b02075
Fournier GP, Alm EJ (2015) Ancestral reconstruction of a Pre-LUCA aminoacyl-tRNA synthetase ancestor supports the late addition of Trp to the genetic code. J Mol Evol 80:171–185. https://doi.org/10.1007/s00239-015-9672-1
Frenkel-Pinter M, Haynes JW, Martins C et al (2019) Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. Proc Natl Acad Sci 116:16338–16346. https://doi.org/10.1073/pnas.1904849116
Giacobelli VG, Fujishima K, Lepsik M, et al (2021) In vitro evolution reveals primordial RNA-protein interaction mediated by metal cations. https://doi.org/10.1101/2021.08.01.454623
Granold M, Hajieva P, Toşa MI et al (2018) Modern diversification of the amino acid repertoire driven by oxygen. Proc Natl Acad Sci 115:41–46. https://doi.org/10.1073/pnas.1717100115
Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185:862–864
Gugisch R, Kerber A, Kohnert A et al (2015) Chapter 6—MOLGEN 50, a molecular structure generator. In: Basak SC, Restrepo G, Villaveces JL (eds) Advances in mathematical chemistry and applications. Bentham Science Publishers, United Arab Emirates, pp 113–138
Higgs PG, Pudritz RE (2009) A Thermodynamic basis for prebiotic amino acid synthesis and the nature of the first genetic code. Astrobiology 9:483–490. https://doi.org/10.1089/ast.2008.0280
Ilardo M, Meringer M, Freeland S et al (2015) Extraordinarily adaptive properties of the genetically encoded amino acids. Sci Rep 5:9414. https://doi.org/10.1038/srep09414
Ilardo M, Bose R, Meringer M et al (2019) Adaptive properties of the genetically encoded amino acid alphabet are inherited from its subsets. Sci Rep 9:12468. https://doi.org/10.1038/s41598-019-47574-x
Johnson AP, Cleaves HJ, Dworkin JP et al (2008) The miller volcanic spark discharge experiment. Science 322:404–404. https://doi.org/10.1126/science.1161527
Kimura M, Akanuma S (2020) Reconstruction and characterization of thermally stable and catalytically active proteins comprising an alphabet of ~ 13 amino acids. J Mol Evol 88:372–381. https://doi.org/10.1007/s00239-020-09938-0
Koga T, Naraoka H (2017) A new family of extraterrestrial amino acids in the murchison meteorite. Sci Rep 7:636. https://doi.org/10.1038/s41598-017-00693-9
Kotra RK, Shimoyama A, Ponnamperuma C, Hare PE (1979) Amino acids in a carbonaceous chondrite from Antarctica. J Mol Evol 13:179–183. https://doi.org/10.1007/BF01739477
Lavergne T, Degardin M, Malyshev DA et al (2013) Expanding the scope of replicable unnatural DNA: stepwise optimization of a predominantly hydrophobic base pair. J Am Chem Soc 135:5408–5419. https://doi.org/10.1021/ja312148q
Longo LM, Lee J, Blaber M (2013) Simplified protein design biased for prebiotic amino acids yields a foldable, halophilic protein. Proc Natl Acad Sci 110:2135–2139. https://doi.org/10.1073/pnas.1219530110
Longo LM, Tenorio CA, Kumru OS et al (2015) A single aromatic core mutation converts a designed “primitive” protein from halophile to mesophile folding: aromatic amino acids and mesophile adaptation. Protein Sci 24:27–37. https://doi.org/10.1002/pro.2580
Longo LM, Despotović D, Weil-Ktorza O et al (2020) Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion. Proc Natl Acad Sci 117:15731. https://doi.org/10.1073/pnas.2001989117
Lu Y, Freeland SJ (2008) A quantitative investigation of the chemical space surrounding amino acid alphabet formation. J Theor Biol 250:349–361. https://doi.org/10.1016/j.jtbi.2007.10.007
Malyshev DA, Dhami K, Lavergne T et al (2014) A semi-synthetic organism with an expanded genetic alphabet. Nature 509:385–388. https://doi.org/10.1038/nature13314
Martin W, Russell MJ (2007) On the origin of biochemistry at an alkaline hydrothermal vent. Philos Trans R Soc B Biol Sci 362:1887–1926. https://doi.org/10.1098/rstb.2006.1881
Mayer-Bacon C, Freeland SJ (2021) A broader context for understanding amino acid alphabet optimality. J Theor Biol 520:110661. https://doi.org/10.1016/j.jtbi.2021.110661
Mayer-Bacon C, Agboha N, Muscalli M, Freeland S (2021) Evolution as a guide to designing xeno amino acid alphabets. Int J Mol Sci. https://doi.org/10.3390/ijms22062787
Meringer M, Cleaves HJ, Freeland SJ (2013) Beyond terrestrial biology: charting the chemical universe of α-amino acid structures. J Chem Inf Model 53:2851–2862. https://doi.org/10.1021/ci400209n
Moosmann B (2021) Redox biochemistry of the genetic code. Trends Biochem Sci 46:83–86. https://doi.org/10.1016/j.tibs.2020.10.008
Naraoka H, Shimoyama A, Harada K (1999) Molecular distribution of monocarboxylic acids in Asuka carbonaceous chondrites from Antarctica. Orig Life Evol Biosph 29:187–201. https://doi.org/10.1023/A:1006547127028
Parker ET, Cleaves HJ, Dworkin JP et al (2011) Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment. Proc Natl Acad Sci 108:5526–5531. https://doi.org/10.1073/pnas.1019191108
Philip GK, Freeland SJ (2011) Did evolution select a nonrandom “alphabet” of amino acids? Astrobiology 11:235–240. https://doi.org/10.1089/ast.2010.0567
Pizzarello S (2007) The chemistry that preceded life’s origin: a study guide from meteorites. Chem Biodivers 4:680–693. https://doi.org/10.1002/cbdv.200790058
Pizzarello S, Schrader DL, Monroe AA, Lauretta DS (2012) Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution. Proc Natl Acad Sci 109:11949–11954. https://doi.org/10.1073/pnas.1204865109
Remusat L, Derenne S, Robert F, Knicker H (2005) New pyrolytic and spectroscopic data on orgueil and murchison insoluble organic matter: a different origin than soluble? Geochim Cosmochim Acta 69:3919–3932. https://doi.org/10.1016/j.gca.2005.02.032
Ross D (2008) A quantitative evaluation of the iron-sulfur world and its relevance to life’s origins. Astrobiology 8:267–272. https://doi.org/10.1089/ast.2007.0199
Shibue R, Sasamoto T, Shimada M et al (2018) Comprehensive reduction of amino acid set in a protein suggests the importance of prebiotic amino acids for stable proteins. Sci Rep 8:1227. https://doi.org/10.1038/s41598-018-19561-1
Shimoyama A, Katsumata H (2001) Polynuclear aromatic thiophenes in the murchison carbonaceous chondrite. Chem Lett 30:202–203. https://doi.org/10.1246/cl.2001.202
Simkus DN, Aponte JC, Elsila JE et al (2019) Methodologies for analyzing soluble organic compounds in extraterrestrial samples: amino acids, amines, monocarboxylic acids, aldehydes, and ketones. Life 9:47. https://doi.org/10.3390/life9020047
Trifonov EN (2000) Consensus temporal order of amino acids and evolution of the triplet code. Gene 261:139–151. https://doi.org/10.1016/S0378-1119(00)00476-5
Tuller T, Birin H, Gophna U et al (2010) Reconstructing ancestral gene content by coevolution. Genome Res 20:122–132. https://doi.org/10.1101/gr.096115.109
Wächtershäuser G (1992) Groundworks for an evolutionary biochemistry: the iron-sulphur world. Prog Biophys Mol Biol 58:85–201. https://doi.org/10.1016/0079-6107(92)90022-X
Weber AL, Miller SL (1981) Reasons for the occurrence of the twenty coded protein amino acids. J Mol Evol 17:273–284. https://doi.org/10.1007/BF01795749
Weiss MC, Preiner M, Xavier JC et al (2018) The last universal common ancestor between ancient earth chemistry and the onset of genetics. PLOS Genet 14:e1007518. https://doi.org/10.1371/journal.pgen.1007518
White HB (1976) Coenzymes as fossils of an earlier metabolic state. J Mol Evol 7:101–104. https://doi.org/10.1007/BF01732468
Wong JT-F, Bronskill PM (1979) Inadequacy of prebiotic synthesis as origin of proteinous amino acids. J Mol Evol 13:115–125. https://doi.org/10.1007/BF01732867
Zhao YH, Abraham MH, Zissimos AM (2003) Fast calculation of Van der Waals volume as a sum of atomic and bond contributions and its application to drug compounds. J Org Chem 68:7368–7373. https://doi.org/10.1021/jo034808o
Zherebker A, Kostyukevich Y, Volkov DS et al (2021) Speciation of organosulfur compounds in carbonaceous chondrites. Sci Rep 11:7410. https://doi.org/10.1038/s41598-021-86576-6
Acknowledgements
R. H.’s work was supported in part by the NASA Astrobiology Institute through funding awarded to the Goddard Center for Astrobiology under proposal 13-13NAI7-0032. We would like to thank UMBC undergraduate Ian Squires for his help in generating the data shown in Fig. 9, along with two anonymous reviewers and the JME editor Andrew Ellington for helpful insights which have improved this manuscript considerably.
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CM-B, SF: Conceptualization. MM, RH: Resources. CM-B, SF, MM: Methodology. CM-B, RH, JCA: Data curation. CM-B, MM: Software. CM-B, SF: Investigation. CM-B: Visualization. CM-B, MM, RH, SF: Writing—original draft. CM-B, MM, RH, JCA, SF: Writing—review and editing. SF: Project administration.
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Mayer-Bacon, C., Meringer, M., Havel, R. et al. A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet. J Mol Evol 90, 307–323 (2022). https://doi.org/10.1007/s00239-022-10061-5
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DOI: https://doi.org/10.1007/s00239-022-10061-5