The limits of metabolic heredity in protocells

Abstract

The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H 2 and CO 2 , the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here, we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in protometabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO 2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids and amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO 2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO 2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO 2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

Biophysical Interactions Underpin the Emergence of Information in the Genetic Code

“…While much still needs to be done, the concept of a spontaneous protometabolism is no longer an appeal to magic. Going further, modelling shows that catalytic positive feedbacks from nucleotide cofactors could drive flux through protometabolism, giving rise to autotrophic protocells growing from CO2 and H2 [59]. If RNA polymerization could occur within these replicating protocells, the emergence of the genetic code through weak biophysical interactions between amino acids and cognate bases could solve the RNA-world problem along the lines postulated by Woese [11].…”

“…As observed by Walker and Davies, "biological information has an additional quality which may roughly be called 'functionality' -or 'contextuality' -that sets it apart from a collection of mere bits as characterized by its Shannon information content." [55] The simplest solution to this near-intractable problem is to assume that the core of metabolism is thermodynamically and kinetically favoured in a propitious environment [56][57][58], so the first RNA genes only had to enhance flux through the protometabolic network [59]. But that presumes a lot from prebiotic chemistry, to the point that Orgel memorably dismissed it as 'an appeal to magic' [60].…”

How did life become cellular?

“…A recent publication by Nunes Palmeira et al . [ 11 ] is unique among computational protocell simulations because it is devoid of genes and is based entirely on chemical flux through a protometabolic network. As a result, the model can investigate potential protocell dynamics prior to the evolution of genetic control and natural selection.…”

“…Protocells were previously shown to have been stabilized by nucleobases [ 6 ]. Here, they are growing and dividing owing to the presence of catalytic nucleotides [ 11 ]. Nucleotide-driven catalysis could have been further enhanced by the polymerization of nucleotides into short nucleic acids, and the protocells that contained them would have outcompeted protocells that did not [ 14 , 15 ].…”

“…These simulations, however, all assume that some kind of heritable genes, such as those imagined by the RNA World hypothesis, already exist, and that evolution is acting on those genes as units of selection. A recent publication by Nunes Palmeira et al [11] is unique among computational protocell simulations because it is devoid of genes and is based entirely on chemical flux through a protometabolic network. As a result, the model can investigate potential protocell dynamics prior to the evolution of genetic control and natural selection.…”