About two years ago, I started on a project to probe the mystery of how the self-replication of cells could evolve to the high accuracy it has in all life. I was especially interested in whether the development of accurate replication could have occurred through the slow, gradual process of evolution that is assumed by the “continuity principle.”
The continuity principle has been described by evolutionary biologist Eugene Koonin as the “…general Darwinian principle… [that] evolution must proceed via consecutive, manageable steps, each one associated with a demonstrable increase in fitness.” While Darwin insisted on very small steps of increasing fitness, we now know that there are many exceptions to this rule. Major evolutionary changes can occur in a noncontinuous way, as sudden and dramatic increases in fitness. We call these jumps in fitness saltations.
Only living cells replicate themselves. Genes made of DNA replicate themselves directly and also code for the replication of all the cellular constituents, including proteins. In modern cells, genes and (indirectly) proteins are replicated with over 99.9999% accuracy. I was interested in how high replication fidelity evolved at life’s beginning, and whether such evolution followed the continuity principle.
The model I developed deals with two critical biological parameters possessed by all living cells, and presumably by proto-cells at the origin of life as well. These parameters are the probability of the survival of cells between cell divisions and the degree of fidelity of replication.
Using a computer-based simulation model, I obtained data on the growth rate of cell populations. I made the following assumptions: 1. Cells can divide into two new daughter cells. 2. There is a period of cell growth between each division, during which cells may perish or survive, depending on their probability of survival. 3. Cells with high replication fidelity are more likely to pass on their survival probability than cells with low replication fidelity.
The data were generated using various inputs of both parameters (from 0 to 100%) and a Monte Carlo approach, which converts probabilities to actual simulated data. To produce significant results, thousands of replicate runs were done for each condition.
I found that if the starting values of survival probability and replication fidelity were each less than 70%, all the cells died out by the 6th generation. Even with perfect replication fidelity (100%) a starting value for survival probability below 63% will lead to eventual extinction of the population.
Contrary to expectation, cell populations with very low (even zero) replication fidelity can survive and evolve, although barely. However, the lower the accuracy of replication, the higher the initial survival probability must be to maintain population survival. With no replication fidelity at all, the minimum value of survival probability to avoid extinction is 95%.
Furthermore, at low levels of survival probability, improvement of either survival probability or replication fidelity is not possible, and neither parameter can evolve to more advantageous levels. This further suggests that the earliest life forms must have begun with a probability of survival of at least 50%.
The results presented so far are consistent with saltation rather than a continuous, gradual process in the development of replication fidelity and survival probability. More direct evidence for this was derived by a statistical approach.
Continuity involves a process that progresses in small steps where each step produces a meaningful difference in an outcome compared to the previous step. We can assess such meaningful differences by tests of statistical significance. Continuity can then be measured by the smallest increase of some input that results in a statistically significant difference in outcome.
I found that when the survival probability was high, there was strong evidence for a continuous evolution of replication fidelity. However, at survival probabilities lower than 60%, there was clear evidence for gaps in continuity, and these gaps got larger as the survival probabilities decreased.
During the origin of life, it’s likely that both the probability of survival and replication fidelity were far from perfect. They were possibly quite low at some early points in life’s development. A lack of continuity in the evolution of both of these critical aspects of living cells strongly suggests that early life could not have evolved without some dramatic jumps in the levels of both survival probability and the accuracy of cellular self-replication.
These results are universal and don’t depend on the specific biochemical mechanisms of cell replication or survival. They can be applied to any living, self-replicative system, including the modern information storage and translation system of DNA and protein synthesis, an RNA-world paradigm of collections of individual self-replicating and catalyzing ribozymes, or any other as yet unknown primitive system for replication of cellular components and characteristics.
A technical peer-reviewed paper describing this project and its results has been accepted for publication in the scientific journal Acta Biotheoretica (published by Springer Press). While the paper is still in press, you can access the pre-print pdf from my web site at https://sygarte.com/paper/