Consider a yeast cell and a human cell, what will happen if the genes that are essential for survival of yeast are substituted by their human orthologs? Coding sequences of these genes have diverged almost a billion years ago, but have their functions? Kachroo et. al. [1] found almost 50% of essential genes, out of nearly 400 chosen for study, can be replaced. To the question of what factors determine replaceability, they found although sequence similarity explains some aspect of it, the major determinant seems to be the biological pathways to which these genes belong. Genes making protein products having enzymatic role in metabolism, sterol biosynthesis and part of the proteasome are more amenable to humanization compared to genes involved in DNA replication, repair or cell growth. This might indicate that the machinery for some biological processes/modules have evolved very differently in the two organisms, whereas some of them have been kept as they are. What could be the reasons for slower evolution of those biological modules?
- Kachroo AH, Laurent JM, Yellman CM, Meyer AG, Wilke CO, Marcotte EM.
Evolution. Systematic humanization of yeast genes reveals conserved functions and genetic modularity. Science. 2015 May 22; 348(6237):921-5.