Grave Concern about Metabolism First Origin-of-Life Scenarios
Metabolic Cycles on Early Earth Deemed Implausible by Famous Origin-of-Life Researcher
When someone speaks to you from beyond the grave, you better pay attention. A paper, submitted posthumously on behalf of the late origin-of-life researcher Leslie Orgel, has just been published in the journal PLoS Biology. And Orgel has a message for origin-of-life researchers: metabolic cycles, and consequently, metabolism-first scenarios are unrealistic. This wake-up call causes a grave concern for evolutionary explanations of life’s beginnings.
Evolutionary origin-of-life models require pathways that ultimately generate two of life’s defining biochemical features: self-replication and metabolism. As such, there are two fundamental approaches to explain life’s beginning from an evolutionary standpoint: (1) replicator-first, and (2) metabolism-first scenarios.
From a molecular standpoint, self-replication describes the capacity of a complex molecule to guide its own reproduction, typically by serving as a template that directs the assembly of chemical constituents into molecules identical to it self.
DNA is a self-replicating molecule. DNA not only orchestrates its own reproduction, but also houses the information needed to carry out the cell’s operation. Prior to cell division, the cell’s biochemical machinery generates two identical DNA molecules from the “parent” DNA. These two molecules become partitioned into the daughter cells during the cell division process. In this way, the information needed to operate the cell is passed on to the next generation.
Metabolism defines the entire set of chemical pathways in the cell. Foremost are the ones that chemically transform relatively small molecules. Metabolic pathways: (1) generate chemical energy through the controlled breakdown of fuel molecules like sugars and fats; and (2) produce, in a stepwise fashion, the building blocks needed to assemble proteins, DNA, RNA, and cell membrane and cell wall components. Life’s metabolic pathways often share many molecules. The shared molecules serve as connection points, causing the cell’s metabolic routes to interconnect into complex, reticulated webs of chemical pathways.
Replicator-first scenarios face significant, perhaps insurmountable hurdles. For a detailed discussion of problems with replicator-first explanations for the origin of life see the book I wrote with Hugh Ross, Origins of Life: Biblical and Evolutionary Models Face Off. Also see an earlier article I wrote for the Today’s New Reason To Believe feature.
In the face of the seemingly intractable difficulties with replicator-first scenarios, some origin-of-life researchers postulate that once prebiotic materials formed, these relatively small molecules self-organized to form chemical cycles and networks of chemical reactions that over time gave rise to life’s metabolic systems. Once encapsulated or sequestered within a membrane, these complex, reticulated systems of reactions became the first prebionts.
According to this view, molecular self-replicators emerged later along with the enzymes that catalyzed each step in the chemical cycles and networks. Some proponents of metabolism-first scenarios maintain that these cycles and networks closely resembled the metabolic pathways found in the cell today. In other words, “metabolism recapitulates biogenesis.” Metabolism-first adherents suggest that either: (1) individual chemical species that were part of these cycles and networks catalyzed these same reactions—a type of autocatalysis; or (2) that mineral surfaces catalyzed the protometabolic pathways.
(I also critiqued metabolism-first scenarios in a past TNRTB article).
Leslie Orgel was critical of metabolism-first ideas and produced a manuscript before his death detailing some of his concerns.
Acknowledging the importance of metabolism-first ideas for the origin-of-life question, Orgel notes,
“If complex cycles analogous to metabolic cycles could have operated on primitive Earth, before the appearance of enzymes or other informational polymers, many of the obstacles to the construction of a plausible scenario for the origin of life would disappear.”
Still, metabolism-first models can only be viewed as truly valid if they are chemically plausible. According to Orgel, chemical plausibility must be assessed based on the efficiencies and specificities of the proto-metabolic cycles in the context of the conditions of the early Earth. Orgel illustrates the importance of these criteria for assessing the likelihood of metabolism-first scenarios by applying them to the reverse citric acid cycle.
Certain bacteria utilize the reverse citric acid cycle to fix carbon, converting carbon dioxide and water into organic compounds. Some origin-of-life researchers have proposed that the reverse citric acid cycle was one of the first metabolic pathways to emerge and that its genesis pre-dated the origin of information-based molecules like RNA (and proteins and DNA).
Orgel concludes that the conditions of the early Earth permit the reverse citric acid cycle to operate sufficiently provided that it is stable for long periods of time and that disruptive side reactions don’t reduce the overall efficiency of the cycle below fifty percent. On the other hand, the reverse citric acid cycle (in fact, all proto-metabolic cycles) appears to be implausible on early Earth because the catalysts needed to drive the cycle lack the necessary specificity.
The reverse citric acid cycle consists of eleven steps, each one requiring a specific mineral catalyst on the early Earth. The cycle also depends on six fundamentally distinct chemical transformations. Inside cells, this metabolic process employs complex enzyme catalysts possessing high specificities and capacities for molecular-level discrimination among the components of the cycle. Orgel rightly argues that it’s not likely that the right types of minerals needed to carry out these reactions would coexist at a particular locale on the early Earth in such a way to support the reverse citric acid cycle.
The specificity problem becomes exacerbated if the reverse citric acid cycle is to evolve toward greater complexity, a requirement if life is to originate from a proto-metabolic cycle. Presumably, evolution of complexity results when additional reaction sequences are appended onto the core reactions of the cycle. According to Orgel,
“Given the difficulty of finding an ensemble of catalysts that are sufficiently specific to enable the original cycle, it is hard to see how one could hope to find an ensemble capable of enabling two or more.”
Discrimination, or more appropriately, the lack of discrimination is also a problem. Many of the compounds in the reverse citric acid cycle share structural similarities. Enzymes inside of cells can readily distinguish these similar compounds, but mineral catalysts can’t. This lack of specificity will cause key components of the cycle to be siphoned off into unwanted disruptive side reactions. Over time, this disruption will more than likely drive the efficiency of the cycle below fifty percent, thus quenching it.
The problems identified for the reverse citric acid cycle apply to any conceivable proto-metabolic cycle on the early Earth.
Consequently, even though metabolism-first scenarios are becoming more prominent within the evolutionary paradigm for the origin-of-life, they ultimately provide little hope to explain the emergence of life from inanimate systems. Orgel’s last words to the origin-of-life community admonish both metabolism-first and replicator-first adherents,
“solutions offered by supporters of geneticist or metabolist scenarios that are dependent on ‘if pigs could fly’ hypothetical chemistry are unlikely to help.”