Periodic Reporting for period 4 - BALANCED LETHALS (Untangling the Evolution of a Balanced Lethal System)
Período documentado: 2023-08-01 hasta 2025-01-31
In a ‘balanced lethal system’ only offspring that possess two different versions of a particular chromosome survive. Hence, this hereditary disease results in a huge die-off: half the offspring receive the same version twice from both parents and die. How could such a maladaptive situation evolve? 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. We uncover the mechanism that generated the two different chromosome versions and use evolutionary modeling to understand how the balanced lethal system could have become established. 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 is not as widely recognized as it should be.
We show that an unequal exchange between two homologues of the ancestral chromosome 1 resulted in two versions of chromosome 1, A and B, that each lack a unique large chunk of DNA covering many genes, while having the DNA chunk missing on the alternate version duplicated. As a consequence, both versions are required to possess a full set of genes. This explains why all adults have both A and B, and why half of their offspring, those that receive either the A or the B version twice (a 50% chance according to the rules of Mendelian inheritance), are not viable. Via evolutionary modeling we explore how a balanced lethal system can spread in a population. The chance is small, in line with the observation that balanced lethal systems are rare in nature, but not zero either. Importantly, once the balanced lethal system has become fixed, it is resistant to being invaded by the ancestral version of the chromosome, because individuals with both the ancestral and one of the derived chromosomes will for many genes have not two but one or three copies, which can be expected to negatively impact fitness. Furthermore, we show that within the genus Triturus (which covers about ten species) the gene content of the two versions of chromosome 1, A and B, is highly conserved. Strikingly, the evolutionary relationships of Triturus’ chromosome 1 distinctly differ from the rest of the genome. We conclude the ancestral chromosome must have been transferred in its entirety into the Triturus ancestor by introgressive hybridization, just before it split into the A and B version. In another evolutionary modelling, we show that, under certain conditions, a supergene system could collapse into a balanced lethal system, but our empirical data actually does not align with this scenario. We also disprove a hypothesis on the origin of the balanced lethal system in Triturus that proposes the A and B versions of chromosome 1 are the ‘ghost of sex chromosomes past’ by showing that Triturus’ chromosome 1 is not equivalent to the sex chromosome in its sister lineage Lissotriton. The main conclusion of a study on gene expression in healty versus diseased embryos is that the unlucky embryos dying from the balanced lethal systems are not killed by a single gene malfunctioning but that, compared to healthy embryos, there is a massive number of genes failing. We are still working to complete the Triturus genome (which is assembled into chromosomes at the moment of writing). To conduct our work we developed several packages / protocols that will be useful for researchers working on other topics. We produced a lot of public engagements, including videos, public lectures, popular articles and a recurring practical on the balanced lethal system we teach to second year Bachelor biology students.
My team solves a longstanding evolutionary mystery: the evolution of balanced lethal systems in nature. We achieve this goal by combining state-of-the-art techniques and the latest evolutionary theory. We describe in detail the genomic architecture underlying the best-known balanced lethal system, discovered over two centuries ago in Triturus newts and previously only worked out at the karyotypic level over four decades ago. We provide a scenario on how this ridiculously wasteful system could have originated. The Triturus balanced lethal system is a prime example of the intelligent design that is evolution by natural selection.