Genome evolution is driven by gene expression‐generated biophysical constraints through RNA‐directed genetic variation: A hypothesis

Abstract

The biogenesis of RNAs and proteins is a threat to the cell. Indeed, the act of transcription and nascent RNAs challenge DNA stability. Both RNAs and nascent proteins can also initiate the formation of toxic aggregates because of their physicochemical properties. In reviewing the literature, I show that co-transcriptional and co-translational biophysical constraints can trigger DNA instability that in turn increases the likelihood that sequences that alleviate the constraints emerge over evolutionary time. These directed genetic variations rely on the biogenesis of small RNAs that are transcribed directly from challenged DNA regions or processed from the transcripts that directly or indirectly generate constraints or aggregates. These small RNAs can then target the genomic regions from which they initially originate and increase the local mutation rate of the targeted loci. This mechanism is based on molecular pathways involved in anti-parasite genome defence systems, and implies that gene expression-related biophysical constraints represent a driving force of genome evolution.

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

“…Although very speculative, there is also the possibility that the DNA of somatic cells challenged by environment-dependent physicochemical parameters produces "parasite-mimicking RNAs" that could form DNA:RNA hybrids in their complementary loci in the germline DNA and locally trigger mutations ( Figure 4G, red arrow). The following supports this possibility: (i) A convergence between RNA-containing extracellular vesicles and viral particles has been described; (ii) RNAs are widely used in all living organisms to cleave or mutate parasitic nucleic acids; and (iii) RNA:DNA hybrids can be genotoxic, for example, RNA:DNA hybrids can induce DNA adenine deamination [72,[168][169][170][171]185,186,[199][200][201][202][203][204]. It would be very interesting in the future to investigate whether some of the 150 chemical modifications of RNAs identified so far could trigger selective mutations in RNA:DNA hybrids [72,[168][169][170][171]185,186,201,202,204].…”

“…RNAs can increase the likelihood of genetic variations in numerous ways [168,169]. Recently, spectra of molecular mechanisms have been described by which physicochemical constraints on RNAs and proteins, at the time of their synthesis, could trigger mutations in their originating genes through the biogenesis of RNA fragments [72,170,171]. Briefly, environmental fluctuations, on the one hand, induce the transcriptional activity of target genes, and thereby generate a greater amount of mRNAs and proteins, and, on the other hand, generate constraints on nascent RNAs and nascent proteins during transcription and translation ( Figure 4E, 1 and 2).…”

RNA meets DNA: The Potential for gene expression to produce short RNA molecules capable of generating DNA mutation and driving genome evolution (Comment on DOI: 10.1002/bies.201700069)

“…In order for a gene to be expressed its genetic code in DNA must be converted into RNA and then protein, but can the very act of gene expression alter the underlying DNA sequence itself? This is the novel hypothesis put forward by Didier Auboeuf , who has proposed several mechanisms which could perform this, and how this feedback of gene expression on DNA sequence could influence genome evolution.…”