Non-Darwinian Molecular Biology

Abstract

With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper “Non-Darwinian Evolution”, where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura’s new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.

Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control

“…Our data are consistent with a model in which new, limited-scope effects can emerge out of highly expressed, poorly conserved transcripts over brief evolutionary periods and contribute, for example, to the fine-tuning of the balance between cell proliferation and differentiation in adult tissues. Our findings experimentally corroborate the constructive neutral evolution theory and highlight the potential role played by neutrally evolving sequences in the evolution of new genomic functions in the primate lineage 4,55,56 . The extent and the impact of this phenomenon on general organismal diversification and adaptation to changing environments remain to be determined and represent fascinating open questions ripe for further exploration.…”

The GC-content at the 5’ends of human protein-coding genes is undergoing mutational decay

“…Although there is a tendency in the life sciences to ascribe all features to natural selection, it is clear, but not widely appreciated, that non-adaptive processes also contribute to evolution (Gould and Lewontin, 1979; Lynch, 2007; Koonin, 2016; Palazzo and Kejiou, 2022). In this manuscript we present evidence that the GC-content of protein-coding gene TSSs is influenced, in part, by local rates of recombination.…”

“…Although there is a tendency in the life sciences to ascribe all features to natural selection, it is clear, but not widely appreciated, that non-adaptive processes also contribute to evolution (Gould and Lewontin, 1979;Lynch, 2007;Koonin, 2016;Palazzo and Kejiou, 2022).…”

mRNA nuclear export: how mRNA identity features distinguish functional RNAs from junk transcripts

“…Despite all these findings, it has been found that selection between codons for translation optimality in humans is weak and the codon distribution in human protein-coding genes is mostly mediated by non-adaptive evolutionary processes, such as GC-biased gene conversion, which elevates local GC-content [ 113 ]. Indeed, it is likely that non-adaptive forces, such as GC-biased gene conversion and mutational bias, act in conjunction with adaptive forces to maintain elevated GC-content at the 5’ end of most protein coding genes [ 27 , 114 ].…”