The Role of Domain Redundancy in Genetic Robustness Against Null Mutations

A key question in molecular genetics is why severe gene mutations often do not result in a detectable abnormal phenotype. Alternative networks are known to be a gene compensation mechanism. Gene redundancy, i.e. the presence of a duplicate gene (or paralog) elsewhere in the genome, also underpins many cases of gene dispensability. Here, we investigated the role of partial duplicate genes on dispensability, where a partial duplicate is defined as a gene that has no paralog but which codes for a protein made of domains, each of which belongs to at least another protein. The rationale behind this investigation is that, as a partial duplicate codes for a domain redundant protein, we hypothesised that its deletion might have a less severe phenotypic effect than the deletion of other genes. This prompted us to (re)address the topic of gene dispensability by focusing on domain redundancy rather than on gene redundancy. Using fitness data of single-gene deletion mutants of Saccharomyces cerevisiae, we will show that domain redundancy is a compensation mechanism, the strength of which is lower than that of gene redundancy. Finally, we shall discuss the molecular basis of this new compensation mechanism.