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The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context.

Song J, Bonner CA, Wolinsky M, Jensen RA - BMC Biol. (2005)

Bottom Line: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates.The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria.The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

View Article: PubMed Central - HTML - PubMed

Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. jian@lanl.gov

ABSTRACT

Background: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size.

Results: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisHb, aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association.

Conclusion: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

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Zoom-in from Fig. 5 showing tyrA synteny for the beta Proteobacteria and the upper-gamma Proteobacteria. The tree shown, based upon 16S rRNA sequences of the indicated organisms, indicates correct branching orders, but (to facilitate presentation) is not strictly correct in proportion. Circled numbers (in violet) indicate deduced evolutionary events for the beta Proteobacteria (see top of Table 5), whereas circled numbers (in pink; see bottom of Table 5) correspond to deduced evolutionary events for the upper-gamma Proteobacteria. Gene organizations of organisms indicated are shown on the right. The dotted outlining of some gene boxes in Coxiella burnetii and in P. syringae indicates pseudogene status.
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Figure 6: Zoom-in from Fig. 5 showing tyrA synteny for the beta Proteobacteria and the upper-gamma Proteobacteria. The tree shown, based upon 16S rRNA sequences of the indicated organisms, indicates correct branching orders, but (to facilitate presentation) is not strictly correct in proportion. Circled numbers (in violet) indicate deduced evolutionary events for the beta Proteobacteria (see top of Table 5), whereas circled numbers (in pink; see bottom of Table 5) correspond to deduced evolutionary events for the upper-gamma Proteobacteria. Gene organizations of organisms indicated are shown on the right. The dotted outlining of some gene boxes in Coxiella burnetii and in P. syringae indicates pseudogene status.

Mentions: Consensus ancestral gene organizations for the most densely represented divisions of Proteobacteria have been deduced as shown at the bottom of Fig. 5. Detailed information that supports a deduced consensus for ancestral gene organizations with respect to beta Proteobacteria, upper-gamma Proteobacteria, and lower-gamma Proteobacteria are shown later (Figs. 6, 7). We suggest that the last common ancestor of all Proteobacteria possessed the gene organization aroQ•pheA>hisHb>tyrA>aroF>cmk>rpsA. This is similar to the synteny that has been retained in general by the beta Proteobacteria and the upper-gamma Proteobacteria. The aroQ•pheA>hisHb>tyrA portion likely specified all the catalytic requirements for conversion of chorismate to PHE and conversion of chorismate to TYR. Chorismate mutase activity specified by the aroQ domain could supply PPA for both PHE and TYR biosynthesis. Likewise, HisHb, widely utilized as an aromatic aminotransferase [49], could also function for both PHE and TYR biosynthesis. Though currently available members of delta and epsilon Proteobacteria exhibit substantial gene scrambling, the various fragmentary linkage patterns seen provide support for the ancestor proposed. Geobacter (and other Delta_1 members) has the aroQ•pheA > tyrA > aroF > cmk > rpsA linkage group (with lytB inserted between cmk and rpsA). Desulfovibrio vulgaris, another delta Proteobacterium (Delta_2) that is highly divergent from Geobacter, has a very interesting pattern of conservation and scrambling. aroQ•pheA > aroF > tyrA has been attached to a complete 7-gene trp operon. hisHb > cmk (not shown in Fig. 5) is completely separated from rpsA. The supraoperonic gene organization shown for D. vulgaris begins with two recently discovered genes, herein denoted aroA' and aroB', that encode enzymes specifying an alternative biochemical route to dehydroquinate [52]. The epsilon Proteobacteria all display significant gene scrambling, but piecemeal evidence for the unscrambled ancestor proposed is present. For example, Campylobacter jejuni possesses an aroQ•pheA > hisHb unit, as well as aroF > lytB > rpsA (Fig. 5). Wollinella succinogenes and Helicobacter hepaticus both possesses an aroF > lytB > rpsA unit.


The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context.

Song J, Bonner CA, Wolinsky M, Jensen RA - BMC Biol. (2005)

Zoom-in from Fig. 5 showing tyrA synteny for the beta Proteobacteria and the upper-gamma Proteobacteria. The tree shown, based upon 16S rRNA sequences of the indicated organisms, indicates correct branching orders, but (to facilitate presentation) is not strictly correct in proportion. Circled numbers (in violet) indicate deduced evolutionary events for the beta Proteobacteria (see top of Table 5), whereas circled numbers (in pink; see bottom of Table 5) correspond to deduced evolutionary events for the upper-gamma Proteobacteria. Gene organizations of organisms indicated are shown on the right. The dotted outlining of some gene boxes in Coxiella burnetii and in P. syringae indicates pseudogene status.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173090&req=5

Figure 6: Zoom-in from Fig. 5 showing tyrA synteny for the beta Proteobacteria and the upper-gamma Proteobacteria. The tree shown, based upon 16S rRNA sequences of the indicated organisms, indicates correct branching orders, but (to facilitate presentation) is not strictly correct in proportion. Circled numbers (in violet) indicate deduced evolutionary events for the beta Proteobacteria (see top of Table 5), whereas circled numbers (in pink; see bottom of Table 5) correspond to deduced evolutionary events for the upper-gamma Proteobacteria. Gene organizations of organisms indicated are shown on the right. The dotted outlining of some gene boxes in Coxiella burnetii and in P. syringae indicates pseudogene status.
Mentions: Consensus ancestral gene organizations for the most densely represented divisions of Proteobacteria have been deduced as shown at the bottom of Fig. 5. Detailed information that supports a deduced consensus for ancestral gene organizations with respect to beta Proteobacteria, upper-gamma Proteobacteria, and lower-gamma Proteobacteria are shown later (Figs. 6, 7). We suggest that the last common ancestor of all Proteobacteria possessed the gene organization aroQ•pheA>hisHb>tyrA>aroF>cmk>rpsA. This is similar to the synteny that has been retained in general by the beta Proteobacteria and the upper-gamma Proteobacteria. The aroQ•pheA>hisHb>tyrA portion likely specified all the catalytic requirements for conversion of chorismate to PHE and conversion of chorismate to TYR. Chorismate mutase activity specified by the aroQ domain could supply PPA for both PHE and TYR biosynthesis. Likewise, HisHb, widely utilized as an aromatic aminotransferase [49], could also function for both PHE and TYR biosynthesis. Though currently available members of delta and epsilon Proteobacteria exhibit substantial gene scrambling, the various fragmentary linkage patterns seen provide support for the ancestor proposed. Geobacter (and other Delta_1 members) has the aroQ•pheA > tyrA > aroF > cmk > rpsA linkage group (with lytB inserted between cmk and rpsA). Desulfovibrio vulgaris, another delta Proteobacterium (Delta_2) that is highly divergent from Geobacter, has a very interesting pattern of conservation and scrambling. aroQ•pheA > aroF > tyrA has been attached to a complete 7-gene trp operon. hisHb > cmk (not shown in Fig. 5) is completely separated from rpsA. The supraoperonic gene organization shown for D. vulgaris begins with two recently discovered genes, herein denoted aroA' and aroB', that encode enzymes specifying an alternative biochemical route to dehydroquinate [52]. The epsilon Proteobacteria all display significant gene scrambling, but piecemeal evidence for the unscrambled ancestor proposed is present. For example, Campylobacter jejuni possesses an aroQ•pheA > hisHb unit, as well as aroF > lytB > rpsA (Fig. 5). Wollinella succinogenes and Helicobacter hepaticus both possesses an aroF > lytB > rpsA unit.

Bottom Line: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates.The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria.The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

View Article: PubMed Central - HTML - PubMed

Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. jian@lanl.gov

ABSTRACT

Background: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size.

Results: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisHb, aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association.

Conclusion: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

Show MeSH
Related in: MedlinePlus