Biology subjects

Von der Dunk, S. H. A.

Publications and source records attributed to Von der Dunk, S. H. A..

3 recordsLinked to original sources

bioRxiv2025

Natural protein structures have evolved exceptional robustness to mutations

Protein structures are often conserved across widely divergent sequences, suggesting high mutational robustness. However, how such robustness emerges through evolution, and how it relates to the underlying sequence-structure map, remains poorly understood. In contrast, the mutational profiles (distribution of structures upon point mutation) of RNA secondary structures are well characterised, exhibiting both high mutational robustness and high evolvability through mutational access to diverse folds. The recent revolution in protein structure prediction now enables analagous large-scale analyses for proteins. Here, we use the structure prediction algorithm ESMFold to systematically investigate the mutational profiles of natural, random, and de novo proteins. Unlike RNA, where functional and random sequences share similar mutational profiles, natural proteins are substantially more robust than random amino acid sequences, suggesting an evolutionary drive toward robustness. They also exhibit limited structural variation among close sequence neighbours, potentially constraining access to new folds. Interestingly, many de novo proteins do resemble random sequences in their mutational profiles, with low robustness relative to established proteins. These findings reveal how gene duplication and de novo gene birth follow distinct evolutionary trajectories toward functional proteins and highlight a potential role for large-effect mutations in the emergence of structural complexity.

evolutionary biology↗

bioRxiv2025

RNA secondary structures are conserved but random

Noncoding RNAs perform a wide range of essential biological functions, and their secondary structures are often conserved by purifying selection. However, such conservation does not necessarily imply that positive selection shaped their evolutionary origins. Here, we test for global signs of positive selection by studying the distribution of secondary structures in naturally occurring noncoding RNA. We find that, to first order, these structures are statistically indistinguishable from those produced by a relatively small set of randomly generated sequences. The distributions are, however, profoundly shaped by a strong bias in the arrival of phenotypic variation, such that only an exponentially small subset of all possible structures is likely to occur in nature. In other words, the secondary structure repertoire of natural noncoding RNAs largely reflects this developmental bias rather than further adaptive fine-tuning. Detecting genuine signatures of selection, beyond randomness, in the distribution of secondary structures, therefore requires careful calibration against appropriate null models that account for the underlying bias. We perform a large-scale and detailed analysis of four extensive datasets covering a wide spectrum of functional RNA classes. We describe one potential signature of adaptation on structure: archaeal ribosomal RNA structures are simpler and more robust than predictions of the sequence null model, and hyperthermophiles are less complex than archaea in other niches, but the effects are relatively small. This example illustrates the difficulty of inferring a creative role for natural selection in shaping evolutionary outcomes for RNA secondary structure.

evolutionary biology↗

bioRxiv2025

The risk of sexual reproduction promotes the evolution of regulation between host and symbionts

Sexual reproduction is a widely spread feature of eukaryotes and was already present in the last eukaryotic common ancestor (LECA). Most extant eukaryotes inherit mitochondria from a single parent, but the mechanisms enforcing uniparental inheritance vary widely. Yet, because the first eukaryotes would not have evolved such mechanisms, sexual cell fusion would have inherently led to mitochondrial mixing. Here, we explore the evolutionary consequences of biparental inheritance of endosymbionts during host-symbiont co-evolution using a multilevel, individual-based model of endosymbiosis. Our results show that biparental inheritance introduces evolutionary conflict, as it facilitates the spread of fast-replicating symbionts, which can drive host populations to extinction. However, in a diverse environment, holobionts diversify and adapt to distinct niches, protecting the population from total collapse caused by selfish symbionts. Moreover, this conflict can be resolved through the evolution of signaling mechanisms that allow hosts to regulate symbiont cell cycles. In many cases, sexually reproducing populations not only survive but also outperform their asexual counterparts. We conclude that sexual reproduction could have appeared early during eukaryogenesis.

evolutionary biology↗