Gain of function. The MRCA of all eukaryotic MSH2 orthologs (leftmost orange circle) already likely functioned in DNA repair (inherited from LUCA, data not shown) and maintenance of DNA repeats. The gene was then coopted in the animal MRCA for a role in apoptosis, and later, in the vertebrate MRCA for a role in somatic hypermutation of immunoglobulin genes. Inferences for ancestral genes (orange circles) are based on experimental GO annotations for the genes shown in green, which are inferred by inheritance for descendants including uncharacterized genes in extant organisms shown in blue. Thus, the ortholog in Bos taurus, for example, will be annotated by PAINT with different functions than the ortholog in Saccharomyces cerevisiae.