Table 1.

Examples of complementation experiments demonstrating the existence of functional equivalence classes in the genetic, metabolic and regulatory networks. The listed examples only represent a small subset of experiments of complementation or gene replacements. They were identified in PubMed with the key words: complementation, gene, function replacement (or displacement), orthologous, parallel, non-orthologous (or non-orthologous) and heterologous. The experiment by Wegscheid et al. [25] has been described in Auletta et al. [12]. Experiments referenced [22–25,51] are described in the text.

function	molecular systems	type of complementation (evolutionary significance)		reference
		recipient(s)	donor(s)
genetic operating system network
tRNAlys aminoacylation	class I (Bacillus subtilis) and class II (Borrelia burgdorferi) Lysyl-tRNA synthetases	non-orthologous replacement (convergence)		[22]
		B. subtilis (Bact.)	B. burgdorferi (Bact.)
tRNAgln aminoacylation	Gln-tRNAgln direct (Escherichia coli) and indirect (B. subtilis) aminoacylation pathways	pathway replacement (convergence)		[23]
		E. coli (Bact.)	B. subtilis (Bact.)
tRNA processing	type A RNase P RNA (E. coli) and MRORP1 protein (Arabidopsis)	non-orthologous replacement (convergence)		[24]
		E. coli (Bact.)	Arabidopsis (Euk.)
TMP synthesis	ThyA (E. coli) and ThyX (Bo. burgdorferi) Thymidylate synthases	non-orthologous replacement (convergence)		[28]
		E. coli (Bact.)	Bo. burgdorferi (Bact.)
protein folding	Rpl25 (Saccharomyces cerevisiae) and TF (E. coli) ribosomal protein chaperones	non-orthologous replacement (convergence)		[26]
		E. coli (Bact.)	S. cerevisiae (Euk.)
tRNA processing	type A (E. coli) and type B (B. subtilis) RNase P RNAs	orthologous replacement (divergence)		[25]
		E. coli (Bact.)	B. subtilis (Bact.)
		B. subtilis (Bact.)	E. coli (Bact.)
ribosome assembly	rRNA/r-protein operons	orthologous replacement (divergence)		[27]
		E. coli (Bact.)	Salmonella typhimurium (Bact.)
			Proteus vulgaris (Bact.)
DNA recombination repair	RAD54 (S. cerevisiae) and AtRAD54 (Arabipdopsis) repair proteins	orthologous replacement (divergence)		[29]
		S. cerevisiae (Euk.)	Arabidopsis (Euk.)
post-translational processing	alg7 (S. cerevisiae) and mv1751 (Methanococcus voltae) N-glycosylation proteins	orthologous replacement (divergence)		[30]
		S. cerevisiae (Euk.)	M. voltae (Arch.)
metabolic network
lipid-linked oligosaccharides translocation	ABC type Wzx (E. coli) and non-ABC-type WlaB (Campylobacter jejuni) flippases	non-orthologous replacement (convergence)		[52]
		E. coli (Bact.)	C. jejuni (Bact.)
inorganic pyrophosphate hydrolysis	soluble (S. cerevisiae) and membrane-bound H+-translocating (Arabidopsis) inorganic pyrophosphatases	non-orthologous replacement (convergence)		[53]
		S. cerevisiae (Euk.)	Arabidopsis (Euk.)
			Chloroflexus aurantiacus (Bact.)
antibiotic resistance	low Mg2+ (Salmonella enterica) and high Mg2+ (E. coli) Polymyxin B resistance pathways	pathway replacement (divergence)		[48]
		E. coli (Bact.)	S. enterica (Bact.)
molecular transport	YopB/YopD (Pseudomonas aeruginosai) and PopB/PopD (Yersinia pestis) proteins	orthologous replacement (divergence)		[54]
		P. aeruginosai (Bact.)	Y. pestis (Bact.)
regulatory network
bacteria motility	pseudotaxis pathway (dependent on a theophylline-riboswitch) and natural chemotaxis pathway (E. coli)	regulatory complementation (convergence)		[51]
		E. coli (Bact.)	synthetic parts
cellular and hormonal regulation	lower and higher eukaryote calmodulins	orthologous replacement (divergence)		[55]
		S. cerevisiae (Euk.)	Xenopus laevis (Euk.)
transcriptional regulation	piD261/Bud32 (S. cerevisiae) and PRPK (human) kinase proteins	partial orthologous replacement (divergence)		[56]
		S. cerevisiae (Euk.)	Homo sapiens (Euk.)