The foundations of genomic complexity in multicellular animals have deep roots in their unicellular prehistory, both in terms of innovations in gene content, as well as the evolutionary dynamics of genome architecture.
The transition to the aggregative stage of Capsaspora owczarzaki, a close unicellular relative to Metazoa, is associated with significant upregulation of orthologs of genes that are important for multicellularity in metazoans.
Sponges and ctenophores lack hypoxia-inducible factors, suggesting that the metazoan last common ancestor could have lived aerobically under severe hypoxia and did not need to regulate its transcription in response to oxygen availability.
Molecular profiling of annelid myocytes reveals that the last common protostome-deuterostome ancestor already possessed a dual musculature, with visceral smooth muscles ensuring digestion and somatic striated muscles ensuring locomotion.
The complex chromatin-based genomic regulatory system controlling developmental gene expression in complex bilaterians predates the evolution of morphological complexity and may have been a prerequisite for the evolution of the first simple multicellular animals.
Genomic evidence suggests that L-gulonolactone oxidase-the terminal enzyme in vitamin C synthesis, which has been repeatedly lost throughout animal evolution-was lost in plants and other photosynthetic eukaryotes following plastid acquisition.