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FRIMEDBIO-Fri prosj.st. med.,helse,biol

The role of whole genome duplication in vertebrate adaptation

Alternative title: Konsekvenser av helgenomduplikasjoner for evolusjon av nye tilpasninger i vertebrater

Awarded: NOK 9.7 mill.

The premise for all natures magnificent variation can be traced back to differences in the DNA code. Hence, if we wish to understand how new adaptations and species arise, we need to understand how new DNA-variation arise through mutations and how these novel variations in the DNA-code gives rise to new functions. One spectacular way that the DNA can change from one generation to the next is through spontaneous doubling of all chromosomes, referred to as a whole genome duplication. Each gene gets a copy of itself on a different chromosome. A central hypothesis in evolutionary biology is that genome duplications spark evolution of novel adaptations. The idea is intuitive: one gene copy can maintain its original function while the other copy is free to evolve new functions. But so far untested. Putting this hypothesis to the test is the main aim of REWIRED project. In REWIRED we use salmonid fish and their ancient genome duplication, dating back 100 million years, as a model system. Measurements of gene regulation across different organs in eight species of salmonid fish will be fed into novel statistical methods to reconstruct evolution of duplicated genes in salmonids. This comparative dataset will allow us to infer if genome duplication promote evolution of novel adaptive gene regulatory phenotypes. Finally, we will put the computational results to the test using state-of-the-art massive parallel reporter assays to measure the enhancer function of >4 million DNA sequences. Combined, the results from REWIRED have provided new understanding of how the most extreme form of DNA mutation - genome duplications - shape the evolution of new traits and adaptations.

The project has been important for the internationalization of the NMBU research group and expansion of the international network. This is exemplified by invitations to contribute to book chapters from leading researchers in the field and several invited talks on the project topic.

Genome evolution - changes in genome size, structure, and function over time - is among the most fundamental process shaping earths biodiversity. Understanding the drivers of genome evolution is therefore a key goal in evolutionary biology. One of the most dramatic genome evolution events is whole genome duplication (WGD). Intriguingly, WGD have played a crucial role in evolution of vertebrates. The complete functional redundancy following WGD has been hypothesized to catalyze evolution of novel adaptations, yet this is still hotly debated. The core of this debate boils down to the relative importance of adaptive versus neutral variation. A decade of research on vertebrate genomes, including our own work on salmonids, has revealed that accelerated evolution in one duplicate copy is a hallmark of genome evolution following WGDs. But does this increased rate of seemingly novel gene functions functional reflect the rise of novel adaptations - or simply loss of purifying selection due to redundancy (i.e. neutral evolution)? REWIRED will address this longstanding and fundamental crux in evolutionary biology by taking advantage of salmonid fish as an emerging and powerful study system. We will apply recently developed computational methods to new extensive functional genomics datasets. This will enable us to overcome existing methodological limitations and distinguish between adaptive and neutral divergence. Finally, we will use bold and innovative experimental approaches, combining state-of-the-art gene editing with detailed molecular phenotyping of in vitro tissue function. This allows us to move beyond statistical signals, linking novel adaptive gene regulation - "REWIRING" - with biological function. The project is expected to bring our knowledge of how WGDs have impacted shape vertebrate genome evolution from a descriptive- towards a mechanistic and functional understanding, and thus make significant impact to the field of genome- and evolutionary biology.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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