Chapter 33 — The Protein Problem

A functional protein requires the correct amino acid sequence folded into the correct three-dimensional shape. The sequence space for a 150-amino-acid protein is approximately 10195 possible sequences. Only a tiny fraction fold into stable, functional structures.

Douglas Axe published research in the Journal of Molecular Biology (2004) measuring how frequently functional enzyme folds appear in that space. His result: approximately 1 functional fold per 1077 possible sequences. Meyer extended the calculation in Signature in the Cell (2009), accounting for the additional requirements of solubility, stability, and biological function, arriving at approximately 1 in 10164. The total number of trials available if every atom in the universe had been randomly assembling amino acid chains since the Big Bang is approximately 1093—seventy-one orders of magnitude short of the less stringent estimate.

The protein problem must be solved before the DNA problem, before the ribosome problem, before the cell membrane problem, and before the homochirality problem discussed in Chapter 12. Each of these is independent. Each must be solved simultaneously with the others before any proto-cell can exist. The probability of solving all of them simultaneously by chance is not calculable—it is not even worth calculating, because the protein problem alone closes the case.

Axe, D.D. Journal of Molecular Biology 341 (2004): 1295–1315. Meyer, S.C. Signature in the Cell. HarperOne, 2009. Chapter 9.

Chapter 34 — The RNA World Cannot Save Itself

The origin-of-life field recognized early that DNA and proteins face a chicken-and-egg problem: DNA cannot replicate without protein enzymes, and proteins cannot be assembled without DNA as an information template and ribosomes as the assembly machinery. The RNA World hypothesis was proposed as a resolution: RNA can act as both information carrier and catalyst. If early life was RNA-based, the chicken-and-egg problem is temporarily dissolved.

The RNA World faces severe problems that researchers in the field acknowledge. RNA does not spontaneously form under plausible prebiotic conditions. The synthesis of nucleotides, their assembly into RNA chains, and the selection of catalytically active sequences all face formidable chemical obstacles. The functional RNA sequence space problem parallels the protein sequence problem: functional ribozymes are rare in sequence space. And the transition from an RNA world to the current DNA-protein world has no known mechanism.

Leslie Orgel, one of the leading origin-of-life researchers and a proponent of the RNA World, wrote in a 2004 review that the hypothesis faces "severe" problems that remain unresolved. The RNA World does not solve the origin of life. It relocates one impossible problem to a slightly earlier time and introduces several additional ones.

Orgel, L.E. "Prebiotic Chemistry and the Origin of the RNA World." Critical Reviews in Biochemistry and Molecular Biology 39 (2004): 99–123. Shapiro, R. "A Simpler Origin for Life." Scientific American (February 2007).