Periodic Reporting for period 3 - DOUBLE EXPRESS (Gene expression level as a keystone to understanding gene duplication: evolutionary constraints, opportunities, and disease)
Período documentado: 2022-01-01 hasta 2023-06-30
In this project we are exploring and testing a hypothesis that different resolution of the evolutionary constraints imposed by the demands of gene expression (how high or low a gene is turned on) can explain these contrasting relationships. We are testing our idea that the opposing constraints on gene-by-gene duplications as compared to WGD channel these different sets of genes into remarkably different evolutionary trajectories. We propose a common mechanism of pathogenicity for many duplication events independent of the biochemical function of the encoded genes, namely competition for cellular resources.
With the availability of abundant high-quality genomics data, now is an opportune time to address these questions. This project is important because it aims to deepen our understanding of the genome, and uncover links between evolutionary patterns and human genetic disease. These are fundamental insights which can be applied across all areas of genomics.
1. Analysed modern genomes to reconstruct the ancestral vertebrate genome structure. This reconstruction reveals many important aspects of vertebrate genome evolution including the number and timing of whole genome duplication events, chromosome fusion events, and the relationships between modern chromosomes. This enables the reliable inference of the relationships between genes, that has previously been a significant challenge, and which opens the possibility of further analysis.(published)
2. Resolution of controversy regarding the animal tree of life. Knowing the correct tree of life is necessary to infer the evolution of important animal features such as the nervous system and the immune system. (published)
3. Quantification of the impact of de novo gene evolution on the origin of genetic novelty. (published)
4. Testing of the hypothesis of the relationship between gene duplication and evolutionary rates. We showed that the genes that tend to be duplicated in small-scale events are those that are faster evolving, and thus less 'important'. (published)
5. Examination and comparison of the genomic and evolutionary properties of genes that are duplicated by small-scale events, whole genome events, and those that remain singleton. (Manuscript in preparation).
6. Testing the evolutionary significance of short peptides in the emergence of new genes. (under review at a journal, and available in BioRXiV).
Other work in progress includes:
1. Analysis of gene expression evolution of WGD duplicates
2. Investigation of the importance of intrinsic disorder (structural) in evolution of duplicate genes
3. investigation of the role of genome duplication in cancers;
4. Experimental investigation of the novel hypothesis of the impact of resource limitation on evolution of gene copy number - exploration of the impacts of WGD in C. elegans model.
Our work on the animal tree of life both resolves a controversial aspect of the tree and also provides an important advance to the methods of tree inference.
We further expect to develop a new paradigm to understand the relationship of gene duplication and expression and show how this can lead to a deeper understanding of human genetic disease.
We are developing C. elegans as a model for understanding the functional and expression impacts of polyploidy. We are testing this in the context of stress response (a controversial hypothesis is that polyploidy increases stress-tolerance).