Template-directed synthesis of a genetic polymer in a model protocell


Contemporary phospholipid-based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel-to-liquid transition temperature1,2, phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles3,4,5 that retain encapsulated oligonucleotides3,6 and are capable of growth and division7,8,9. Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.

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Figure 1: Conceptual model of a heterotrophic protocell.
Figure 2: Ribose permeability of fatty acid based membranes.
Figure 3: Time courses of nucleotide permeation through fatty acid based membranes.
Figure 4: Template-copying chemistry inside vesicles.


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This work was supported by grants from the NASA Exobiology Program (EXB02-0031-0018) and the NSF (CHE-0434507) to J.W.S. J.W.S. is an Investigator of the Howard Hughes Medical Institute. S.S.M. was supported by the NIH (F32 GM07450601). We thank I. Chen, M. Hanczyc, R. Bruckner, T. Zhu and Q. Dufton for discussions, and J. Iwasa for Fig. 1 and Supplementary Fig. 5.

Author Contributions Permeability experiments were performed by S.S.M. J.P.S. performed primer-extension experiments. M.K. synthesized 2′-aminoguanosine. S.T. and D.A.T. contributed to the development of the encapsulated primer-extension system. All authors helped to design the experiments and discussed the results. S.S.M., J.P.S. and J.W.S. wrote the paper.

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Correspondence to Jack W. Szostak.

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The file contains Supplementary Figures S1-S7 with Legends and Supplementary Table S1. (PDF 1451 kb)

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Mansy, S., Schrum, J., Krishnamurthy, M. et al. Template-directed synthesis of a genetic polymer in a model protocell. Nature 454, 122–125 (2008). https://doi.org/10.1038/nature07018

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