Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution

Gustavo Caetano-Anollés, M. Fayez Aziz, Fizza Mughal, Derek Caetano-Anollés

Research output: Contribution to journalReview articlepeer-review


Introduction: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past. Areas covered: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late ‘big bang’ of domain combinations. Expert opinion: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.

Original languageEnglish (US)
Pages (from-to)863-880
Number of pages18
JournalExpert Review of Proteomics
Issue number10
StatePublished - 2021


  • Cotranslational folding
  • RNA structure
  • domains
  • evolution
  • folding
  • modularity
  • multicellularity
  • networks
  • protein structure

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry


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