Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism

Abstract

Enzymes of the gluconeogenic/glycolytic pathway (the Embden-Meyerhof-Parnas (EMP) pathway), the reductive tricarboxylic acid cycle, the reductive pentose phosphate cycle and the Entner-Doudoroff pathway are widely distributed and are often considered to be central to the origins of metabolism. In particular, several enzymes of the lower portion of the EMP pathway (the so-called trunk pathway), including triosephosphate isomerase (TPI; EC 5.3.1.1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12/13), phosphoglycerate kinase (PGK; EC 2.7.2.3) and enolase (EC 4.2.1.11), are extremely well conserved and universally distributed among the three domains of life. In this paper, the distribution of enzymes of gluconeogenesis/glycolysis in hyperthermophiles--microorganisms that many believe represent the least evolved organisms on the planet--is reviewed. In addition, the phylogenies of the trunk pathway enzymes (TPIs, GAPDHs, PGKs and enolases) are examined. The enzymes catalyzing each of the six-carbon transformations in the upper portion of the EMP pathway, with the possible exception of aldolase, are all derived from multiple gene sequence families. In contrast, single sequence families can account for the archaeal and hyperthermophilic bacterial enzyme activities of the lower portion of the EMP pathway. The universal distribution of the trunk pathway enzymes, in combination with their phylogenies, supports the notion that the EMP pathway evolved in the direction of gluconeogenesis, i.e., from the bottom up.

Figure 1.

Phylogenetic tree of triosephosphate isomerases (TPIs; EC 5.3.1.1) generated with the neighbor-joining (NJ) method (Saitou and Nei 1987) as described in Materials and methods. The T. maritima TPI sequence used for the analysis is based on Schurig et al. (1995b). The relevant four-digit gene identification numbers (encoding for the TPIs shown) or respective GenBank database accession codes are shown after the species names. Numbers above the nodes are from the NJ bootstrap analysis, whereas those below the nodes are derived from maximum parsimony bootstrap analysis (both analyses are results of 500 bootstrap replications rounded to 100% values). Only those values greater than or equal to 50% are shown. The bar (0.1) denotes pair-wise distance estimates of the expected number of amino acid replacements per site (Thompson et al. 1994). Archaeal and eukaryotic sequences are in bold text and underlined, respectively.

Figure 2.

Phylogenetic tree of glyceraldehyde-3-phosphate dehydrogenases (phosphorylating; EC 1.2.1.12) generated with the neighbor-joining method. Short stretches of amino acid residues were removed from the Borrelia (4) and Tritrichomonas (11) sequences to maintain alignment based on comparison with crystal structure data. See Figure 1 caption for further explanation.

Figure 3.

Phylogenetic tree of phosphoglycerate kinases (PGKs; EC 2.7.2.3) generated with the neighbor-joining method. The T. maritima PGK sequence used is based on Schurig et al. (1995b). See Figure 1 caption for further explanation.

Figure 4.

Phylogenetic tree of enolases (EC 4.2.1.11) generated with the neighbor-joining method. Three residues within the C-terminus of the Haemophilus influenzae sequence (419–421) were removed to maintain the alignment based on comparison with crystal structure data. See Figure 1 caption for further explanation.