We published two articles focusing on the replaceability of yeast genes with their human equivalents, particularly the duplicated human genes.
- Humanization of yeast genes with multiple human orthologs reveals functional divergence between paralogs. This completes most of the testable essential gene humanizations in yeast. This work demonstrated that the duplicated human genes still retained functional similarity; however, differentially. The systematic assays allowed us to identify the features explaining the divergence between human paralogs.
- Systematic humanization of the yeast cytoskeleton discerns functionally replaceable from divergent human Genes. In this work, we focused on Eukaryotic cytoskeletal families (conserved back to Opisthokonts). These genes are particularly interesting because of having undergone extensive duplications across broad eukaryotic clades. After ~1 billion years of divergence between humans and yeast, we wondered, to what extent were core elements of the yeast cytoskeleton humanizable. We found several cystoskeletal elements in yeast replaceable by their human counterparts (Actins, Myosins, Tubulins and Septins), albeit only a subset from an orthogroup. The study appears on the Cover of the Genetics journal.
Summary of the Cover “Cytoskeleton genes are responsible for forming the structural (architectural) components of cells and have expanded into multigene families in humans relative to earlier ancestors. In this issue, Garge and colleagues studied the evolutionary divergence of such duplicated genes by “humanizing” yeast, replacing yeast cytoskeletal genes with different versions of the corresponding human genes. This is symbolized in the image by human workers constructing yeast from the inside out, as inspired by Fernand Léger’s “The Builders” and illustrated by Ella Marushchenko.