Structural basis of tRNA synthetase-based selfish killer

Some of the fiercest conflicts in nature are not taking place in the African Savanna or Amazon rainforest but in the microscopic world within cells. These battles are not fought with teeth or claws but with the most miniature weapons of all, genes. In 1976, Richard Dawkins shook our understanding of evolution by putting forward a new and radical idea: genesnot individuals are the substrate for natural selection. In this world view, genes strive for immortality while individuals are nothing but vectors to propagate such selfish genes. Because the genome of the host and selfish genes each have their own agenda, they engage in a constant battle to guarantee their inheritance to the next generations, and thus their survival. Although the existence of selfish genes was highly controversial when first proposed by Dawkins, a growing body of evidence strongly suggests that selfish genes are common in nature. They are now recognized to be a prevalent feature of bacterial, plant, and animal genomes. However, despite their widespread presence across the tree of life, their diversity and molecular mechanisms are still largely unknown. Our research aims to understand how selfish genes work at the atomic level and how the everlasting conflict between selfish genes and their host can lead to unpredictable consequences, such as influencing the process of speciation itself. To do so, we will study in detail a novel class of selfish elements that we recently discovered in nematodes: toxin-antidote elements. We will combine genetics, biochemistry, and structural biology to understand how toxin-antidote elements subvert the laws of Mendelian inheritance and specifically, how a selfish element could evolve from a highly conserved enzyme necessary for synthesizing proteins. Within the genes that make up selfish toxin-antidote elements lies the secret of how they can kill their host and quickly spread in natural populations. Knowledge of how this process happens at the molecular level could guide the development of synthetic tools designed to control the spread of diseases such as Malaria, Dengue, and Zika virus, significant global health burdens, especially in the developing world.

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