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Biology subjects

Krogull, D.

Publications and source records attributed to Krogull, D..

4 recordsLinked to original sources

Evolution of an Aurora Kinase A Inhibitor from an Essential tRNA Synthetase

Gene duplication is a major driver of evolution, yet how it generates fundamentally new molecular functions remains poorly understood. Here, we show how such novelty arose in KLMT-1, a selfish toxin that causes genetic incompatibilities in Caenorhabditis tropicalis. KLMT-1 evolved via duplication of an essential tRNA synthetase but, strikingly, lost its ancestral role in tRNA biology and translation. Instead, KLMT-1 localizes to centrosomes, where it targets Aurora kinase A (AIR-1). This innovation is mediated by a three-amino acid insertion that extends a {beta}-hairpin loop, enabling electrostatic interaction with a regulatory interface on the kinase. Our results demonstrate how changes in selective pressure, combined with minimal modifications in neutrally evolving regions, allow duplicated proteins to access new functional space and evolve entirely new molecular activities.

evolutionary biology↗

A regulatory module driving the recurrent evolution of irreducible molecular complexes.

To sustain life, molecular complexes require the concerted action of multiple proteins, each relying on one another to perform intricate tasks. However, how such interdependent protein interactions evolve in the first place is poorly understood. To address this, we investigated the origins of a group of fast-evolving genetic parasites--toxin-antidote elements--which boil down this dilemma to a simple question: what came first, the toxin or the antidote? By integrating quantitative genetics, biochemistry, and evolutionary genomics, we discovered that toxins and antidotes can arise simultaneously through the duplication of a regulatory module comprising an F-box protein in linkage to its substrate. Our findings provide one solution to the recurrent emergence of mutual dependence in protein complexes and illustrate in detail how complexity can swiftly arise from simplicity.

genomics↗

Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities

Horizontal gene transfer--the movement of genetic material between different species--has been reported across all major eukaryotic lineages, including vertebrates. However, the underlying mechanisms of transfer and their impact on genome evolution are still poorly understood. While studying the evolutionary origin of a selfish element in the nematode C. briggsae, we discovered that Mavericks, ancient viral-like transposons related to giant viruses and virophages, are one of the long-sought vectors of horizontal gene transfer. We found that Mavericks gained a novel herpesvirus-like fusogen in nematodes, leading to the widespread exchange of cargo genes between extremely divergent species, bypassing sexual and genetic barriers spanning hundreds of millions of years. Our results show how the union between viruses and transposons--natures melting pot--causes horizontal gene transfer and ultimately genetic incompatibilities in natural populations.

genomics↗

The evolution of an RNA-based memory of self in the face of genomic conflict

Distinguishing endogenous genes from selfish ones is essential for germline integrity. In animals, small regulatory RNAs play a central role in this process; however, the underlying principles are largely unknown. To fill this gap, we studied how selfish toxin-antidote elements (TAs) evade silencing in the nematode Caenorhabditis tropicalis. We found that the slow-1/grow-1 TA is active only when maternally inherited. Surprisingly, this parent-of-origin effect stems from a regulatory role of the toxins mRNA: maternal slow-1 mRNA--but not SLOW-1 protein--licenses slow-1 expression in the zygote by counteracting piRNAs. Our results indicate that epigenetic licensing-- known to play a role in C. elegans sex-determination--is likely a common mechanism that hinders the spread of selfish genes in wild populations while ensuring a lasting memory of self in the germline.

genetics↗