Computing the origin and evolution of the ribosome from its structure - Uncovering processes of macromolecular accretion benefiting synthetic biology

Gustavo Caetano-Anollés, Derek Caetano-Anollés

Research output: Contribution to journalReview articlepeer-review


Accretion occurs pervasively in nature at widely different timeframes. The process also manifests in the evolution of macromolecules. Here we review recent computational and structural biology studies of evolutionary accretion that make use of the ideographic (historical, retrodictive) and nomothetic (universal, predictive) scientific frameworks. Computational studies uncover explicit timelines of accretion of structural parts in molecular repertoires and molecules. Phylogenetic trees of protein structural domains and proteomes and their molecular functions were built from a genomic census of millions of encoded proteins and associated terminal Gene Ontology terms. Trees reveal a 'metabolic-first' origin of proteins, the late development of translation, and a patchwork distribution of proteins in biological networks mediated by molecular recruitment. Similarly, the natural history of ancient RNA molecules inferred from trees of molecular substructures built from a census of molecular features shows patchwork-like accretion patterns. Ideographic analyses of ribosomal history uncover the early appearance of structures supporting mRNA decoding and tRNA translocation, the coevolution of ribosomal proteins and RNA, and a first evolutionary transition that brings ribosomal subunits together into a processive protein biosynthetic complex. Nomothetic structural biology studies of tertiary interactions and ancient insertions in rRNA complement these findings, once concentric layering assumptions are removed. Patterns of coaxial helical stacking reveal a frustrated dynamics of outward and inward ribosomal growth possibly mediated by structural grafting. The early rise of the ribosomal 'turnstile' suggests an evolutionary transition in natural biological computation. Results make explicit the need to understand processes of molecular growth and information transfer of macromolecules.

Original languageEnglish (US)
Pages (from-to)427-447
Number of pages21
JournalComputational and Structural Biotechnology Journal
StatePublished - 2015


  • Evolutionary genomics
  • Molecular functions
  • Molecular structure
  • Origin of life
  • Phylogenetic analysis
  • Protein structural domains
  • Proteome
  • Ribosomal evolution
  • Translation
  • rRNA

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications


Dive into the research topics of 'Computing the origin and evolution of the ribosome from its structure - Uncovering processes of macromolecular accretion benefiting synthetic biology'. Together they form a unique fingerprint.

Cite this