Abstract
The origin and natural history of molecular functions hold the key to the emergence of cellular organization and modern biochemistry. Here we use a genomic census of Gene Ontology (GO) terms to reconstruct phylogenies at the three highest (1, 2 and 3) and the lowest (terminal) levels of the hierarchy of molecular functions, which reflect the broadest and the most specific GO definitions, respectively. These phylogenies define evolutionary timelines of functional innovation. We analyzed 249 free-living organisms comprising the three superkingdoms of life, Archaea, Bacteria, and Eukarya. Phylogenies indicate catalytic, binding and transport functions were the oldest, suggesting a ‘metabolism-first’ origin scenario for biochemistry. Metabolism made use of increasingly complicated organic chemistry. Primordial features of ancient molecular functions and functional recruitments were further distilled by studying the oldest child terms of the oldest level 1 GO definitions. Network analyses showed the existence of an hourglass pattern of enzyme recruitment in the molecular functions of the directed acyclic graph of molecular functions. Older high-level molecular functions were thoroughly recruited at younger lower levels, while very young high-level functions were used throughout the timeline. This pattern repeated in every one of the three mappings, which gave a criss-cross pattern. The timelines and their mappings were remarkable. They revealed the progressive evolutionary development of functional toolkits, starting with the early rise of metabolic activities, followed chronologically by the rise of macromolecular biosynthesis, the establishment of controlled interactions with the environment and self, adaptation to oxygen, and enzyme coordinated regulation, and ending with the rise of structural and cellular complexity. This historical account holds important clues for dissection of the emergence of biomcomplexity and life.
Highlights
We explored the lifestyle of 358 organisms and filtered out 109 organisms with facultative parasitic or obligate parasitic lifestyles
When we compared the enrichment of horizontally transferred proteins (HTPs) to the enrichment of remaining terminal Gene Ontology (GO) terms, we found that 115 terminal GO terms were significantly associated with HTPs (P < 0.05)
We explored the origin of GO term of molecular function (GOTMF) terms linked to higher level GOMF terms by builfing a trees of functions (ToFs) of terminal GO terms, deriving a timeline of their ages using phylogenomic analysis, and mapping these ages to the higher level 1 and level 2 GO terms
Summary
The main goal of our study was to track the evolutionary history of molecular functions defined at different levels of the DAGmf using an updated and expanded functional dataset
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