Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

Abstract

The accumulation of slightly deleterious mutations in populations leads to the buildup of a genetic load and can cause the extinction of populations of small size. Mutation-accumulation experiments have been used to study this process in a wide variety of organisms, yet the exact mutational underpinnings of genetic loads and their fitness consequences remain poorly characterized. Here, we use an abiotic system of RNA populations evolving continuously in vitro to examine the molecular events that can instigate a genetic load. By tracking the fitness decline of ligase ribozyme populations with bottleneck sizes between 100 and 3000 molecules, we detected the appearance and subsequent fixation of both slightly deleterious mutations and advantageous mutations. Smaller populations went extinct in significantly fewer generations than did larger ones, supporting the notion of a mutational meltdown. These data suggest that mutation accumulation was an important evolutionary force in the prebiotic RNA world and that mechanisms such as recombination to ameliorate genetic loads may have been in place early in the history of life.

Low Selection Pressure Aids the Evolution of Cooperative Ribozyme Mutations in Cells

“…However, at least some RNA fitness landscapes are rough (54), where high selection pressure would doom a population with low diversity to extinction (55). A larger genetic diversity speeds up the evolution of ribozymes (19), but the mutational load that is used to generate this diversity can lead to the extinction of populations, especially at small population sizes (20). This illustrates that a combination of several evolutionary parameters determines the benefit of low or high selection pressure.…”

“…These studies showed that genetic diversity of a starting population increases the rate of adaptive evolution (19), that recombination can benefit an evolving population by reducing mutational load (20), and that two distinct, coevolving ribozymes can diversify such that each ribozyme dominates a different niche (21). In contrast to these RNA evolution studies in vitro and RNA selection experiments in cells, according to our knowledge, no experimental studies have addressed RNA evolution in cells.…”

Is Life Impossible? Information, Sex, and the Origin of Complex Organisms

“…These conditions include the process of recombination among genomes, and the situation where many genotypes produce the same phenotype. Encouragingly, there is a good reason to think that these conditions are relevant for very early organisms (Huynen et al 1996; Woese 1998;Wilke 2001;Wilke et al 2001;Lehman 2003;Santos et al 2003Santos et al , 2004Codoner et al 2006;Szathmáry 2006;Sanjuan et al 2007;Soll et al 2007;Sardanyes et al 2008).The idea that, very early in the history of life, recombination occurred between genomes (i.e., sexual reproduction occurred) is absent in the formulations of Eigen and Schuster. However, the possibility of recombination occurring within populations of early organisms has now been widely accepted by the community of origin-of-life researchers (Woese 1998;Lehman 2003;Santos et al 2003;Santos et al 2004;Szathmáry 2006;Soll et al 2007).…”

The molecular underpinnings of genetic phenomena

“…RNA populations in the precellular world would have been at risk not only for loss of information if their replication was not accurate enough, but also for outright extinction if their population sizes dropped too low. Recently empirical evidence shows that small RNA populations evolving in a test tube (with the aid of protein polymerases) can quickly go extinct through mutational accumulation, but that larger population sizes and beneficial mutations can help protect them (Soll et al, 2007). It is apparent that for a number of reasons early selection pressure for improved replicase fidelity-by ribozymes or proteins-would have been severe.…”