(A) None of the four tested human TRiC/CCT chaperonin genes replaced their yeast counterparts. (B) Similarly, no genes tested in the Origin Recognition Complex (ORC) or the Mini-Chromosome Maintenance (MCM) complex were replaceable. (C) In contrast, 17 of 19 sterol biosynthesis genes were replaceable. In two cases, the yeast gene had two human orthologs, but only one could complement. Human HMGCS1 but not HMGCS2 replaced yeast ERG13; human IDI1 but not IDI2 replaced yeast IDI1. Human PMVK, a non-homologous protein that carries out the same reaction as yeast Erg8 (27), complemented temperature sensitive allele erg8-1.