The evolutionary history of protein fold families and proteomes confirms that the archaeal ancestor is more ancient than the ancestors of other superkingdoms

BMC Evol Biol. 2012 Jan 27;12:13. doi: 10.1186/1471-2148-12-13.


Background: The entire evolutionary history of life can be studied using myriad sequences generated by genomic research. This includes the appearance of the first cells and of superkingdoms Archaea, Bacteria, and Eukarya. However, the use of molecular sequence information for deep phylogenetic analyses is limited by mutational saturation, differential evolutionary rates, lack of sequence site independence, and other biological and technical constraints. In contrast, protein structures are evolutionary modules that are highly conserved and diverse enough to enable deep historical exploration.

Results: Here we build phylogenies that describe the evolution of proteins and proteomes. These phylogenetic trees are derived from a genomic census of protein domains defined at the fold family (FF) level of structural classification. Phylogenomic trees of FF structures were reconstructed from genomic abundance levels of 2,397 FFs in 420 proteomes of free-living organisms. These trees defined timelines of domain appearance, with time spanning from the origin of proteins to the present. Timelines are divided into five different evolutionary phases according to patterns of sharing of FFs among superkingdoms: (1) a primordial protein world, (2) reductive evolution and the rise of Archaea, (3) the rise of Bacteria from the common ancestor of Bacteria and Eukarya and early development of the three superkingdoms, (4) the rise of Eukarya and widespread organismal diversification, and (5) eukaryal diversification. The relative ancestry of the FFs shows that reductive evolution by domain loss is dominant in the first three phases and is responsible for both the diversification of life from a universal cellular ancestor and the appearance of superkingdoms. On the other hand, domain gains are predominant in the last two phases and are responsible for organismal diversification, especially in Bacteria and Eukarya.

Conclusions: The evolution of functions that are associated with corresponding FFs along the timeline reveals that primordial metabolic domains evolved earlier than informational domains involved in translation and transcription, supporting the metabolism-first hypothesis rather than the RNA world scenario. In addition, phylogenomic trees of proteomes reconstructed from FFs appearing in each of the five phases of the protein world show that trees reconstructed from ancient domain structures were consistently rooted in archaeal lineages, supporting the proposal that the archaeal ancestor is more ancient than the ancestors of other superkingdoms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Archaea / genetics*
  • Archaea / metabolism
  • Bacteria / genetics
  • Bacteria / metabolism
  • Biological Evolution*
  • Eukaryota / genetics
  • Eukaryota / metabolism
  • Evolution, Molecular
  • Phylogeny*
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics*
  • Proteome / genetics


  • Proteins
  • Proteome