Pavol Kramár

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Project Title: Investigating Mechanisms of Functional Compensation Between Paralogous Genes in Embryonic Development

Summary: 

Embryonic development is a complex process which requires intricate spatiotemporal coordination at the molecular, cellular, and tissue level. Despite this, loss of gene function may not necessarily lead to phenotypic consequences as developing organisms exhibit genetic robustness.

Paralogous genes arise through genomic duplication events and when gene function is lost in one member of a pair, the other member may functionally compensate for its lost counterpart, either due to genetic redundancy or active mechanisms of genetic compensation. The factors that underlie the maintenance of compensation potential are poorly understood.

The first aim of the PhD project is to investigate paralog compensation through the lens of gene-expression noise, i.e., variation in mRNA copy numbers which stems from the stochastic nature of the processes comprising transcription. We hypothesize that noise is a driver of the maintenance of functional compensation between paralogous genes, as genes with variable transcriptional output might be more likely retained in duplicate to ensure the reliable performance of their shared function.

Complete genetic redundancy is evolutionarily disfavored. Thus, paralogs are likely to functionally diversify shortly after gene birth. However, if paralogs evolve to be expressed in different cells or tissues and/or at different developmental stages, it may be more likely that their shared function is maintained in each. Thus, we also aim to investigate the hypothesis that paralogous genes with divergent spatial and/or temporal expression patterns can compensate for each other if expressed in the right place and time.     

Supervisor:

• Dr Elisabeth Busch-Nentwich

Research