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Untangling the Evolution of a Balanced Lethal System

Periodic Reporting for period 3 - BALANCED LETHALS (Untangling the Evolution of a Balanced Lethal System)

Okres sprawozdawczy: 2022-02-01 do 2023-07-31

In a ‘balanced lethal system’ only offspring that possess two different forms of a particular chromosome survive. Hence, this hereditary disease results in a huge die-off: half the offspring receive the same form twice from both parents and die. How could such a maladaptive situation evolve? A balanced lethal system epitomizes how organisms (including humans) are imperfectly adapted and have to play with the cards that evolution dealt them - an important aspect that, in my opinion, is not as widely recognized as it should be. Crested and marbled newts are the textbook example of a balanced lethal system. By using the latest theoretical and technological advances my team studies the huge and complex newt genome for the first time, to finally understand the counterintuitive evolution of balanced lethal systems.
First and foremost all the sampling and permits needed to be obtained - that all went smoothly. The COVID-19 pandemic did seriously delay labwork, but at this point the methodology for their first main experiment is up and running and the main dataset is being generated. This involves 'sequence capture', a technique that allows a standardized set of genetic markers to be obtained efficiently and economically for a large number of individuals and species. The aim of this first main experiment is reconstructing the genomic architecture of this balanced lethal system at its point of origin. To do so we determine variation between the newt species that express the balanced lethal system, in order to calculate how the relevant genomic region looked like in their common ancestor (living c. 25 million years ago). Furthermore, we compare this genomic region with its equivalent in related newt species that do not suffer from the balanced lethal system. Our public engagement strategy focused on publishing several popular articles, introducing the balanced lethal system to different types of audiences. The second main experiment will encompass the sequencing of entire newt genomes - no easy feat as these are huge, c. 10 x a human genome. The practical work has only just started. Meanwhile, a third main experiment encompasses a simulation study that focuses on determining the range of conditions under which a balanced lethal system could possibly evolve. Preliminary results show that this is a very narrow range indeed.
My team will solve a longstanding evolutionary mystery: the evolution of balanced lethal systems in nature. We will achieve this goal by combining state-of-the-art techniques and the latest evolutionary theory.
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