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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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Phylogenetic tree for trimmed core domains of selected members of the TyrA Superfamily. Acronyms used for the various organisms are given in alphabetical order in Table 2. (A more extensive listing that includes organisms not shown in Fig. 2 and which also is hyperlinked to all of the individual GenBank records is given in Table S1. A similar table that also includes compilation of known and predicted substrate specificities is maintained at AroPath [73]. Lineages possessing experimentally established TyrAa, TyrAp, TyrAc or TyrAc_Δ proteins are indicated by fill colors specified in the legend. Three specificity patterns for the pyridine nucleotide substrate are shown by line colors (see figure box). Although the cyanobacteria are depicted as having NADP+-specific TyrA proteins, some of them can also accept NAD, albeit to a lesser degree. All proteins having an aspartate residue homologous to D-32 of the E. coli NADTyrAc_Δ domain are presumed specific for NAD+. Fusion of TyrA domains with other catalytic domains is indicated within grey boxes (AroQ•TyrA, TyrA•AroF, HisHb•TyrA, and TyrA•AroQ•PheA•ACT) using the convention of a bullet to represent the interdomain area. The boxes overlap any relevant lineages. TyrA proteins having carboxy-terminal fusions with regulatory domains (TyrA•ACT and TyrA•REG) are also shown. The distance scale bar at the bottom left represents substitutions per site.
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Figure 2: Phylogenetic tree for trimmed core domains of selected members of the TyrA Superfamily. Acronyms used for the various organisms are given in alphabetical order in Table 2. (A more extensive listing that includes organisms not shown in Fig. 2 and which also is hyperlinked to all of the individual GenBank records is given in Table S1. A similar table that also includes compilation of known and predicted substrate specificities is maintained at AroPath [73]. Lineages possessing experimentally established TyrAa, TyrAp, TyrAc or TyrAc_Δ proteins are indicated by fill colors specified in the legend. Three specificity patterns for the pyridine nucleotide substrate are shown by line colors (see figure box). Although the cyanobacteria are depicted as having NADP+-specific TyrA proteins, some of them can also accept NAD, albeit to a lesser degree. All proteins having an aspartate residue homologous to D-32 of the E. coli NADTyrAc_Δ domain are presumed specific for NAD+. Fusion of TyrA domains with other catalytic domains is indicated within grey boxes (AroQ•TyrA, TyrA•AroF, HisHb•TyrA, and TyrA•AroQ•PheA•ACT) using the convention of a bullet to represent the interdomain area. The boxes overlap any relevant lineages. TyrA proteins having carboxy-terminal fusions with regulatory domains (TyrA•ACT and TyrA•REG) are also shown. The distance scale bar at the bottom left represents substitutions per site.

Mentions: Our evolutionary analysis is limited by the amount of information that can be managed in a single study, with the focus fixed upon the domain Bacteria (due to the relative density of genome representation for Bacteria in the public databases). However, in order to show where future expansion of the analysis might lead, the selection of TyrA proteins in Fig. 2 are from all three domains of life, i.e., Bacteria, Archaea, and Eukarya (lower eukaryotes and higher plants). For practicality of presentation, numerous orphan (i.e., without close relatives) TyrA sequences are not shown, and not all members of a given group are necessarily included. The main purposes of the radial tree shown in Fig. 2 are: (i) to illustrate that TyrA proteins of major phylogenetic groupings are generally congruent with 16S rRNA groupings and (ii) to convey a snapshot visualization of the overall complexity of the TyrA protein family from the vantage point of its varied substrate specificities as well as its multiple fusion partners.


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

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

Phylogenetic tree for trimmed core domains of selected members of the TyrA Superfamily. Acronyms used for the various organisms are given in alphabetical order in Table 2. (A more extensive listing that includes organisms not shown in Fig. 2 and which also is hyperlinked to all of the individual GenBank records is given in Table S1. A similar table that also includes compilation of known and predicted substrate specificities is maintained at AroPath [73]. Lineages possessing experimentally established TyrAa, TyrAp, TyrAc or TyrAc_Δ proteins are indicated by fill colors specified in the legend. Three specificity patterns for the pyridine nucleotide substrate are shown by line colors (see figure box). Although the cyanobacteria are depicted as having NADP+-specific TyrA proteins, some of them can also accept NAD, albeit to a lesser degree. All proteins having an aspartate residue homologous to D-32 of the E. coli NADTyrAc_Δ domain are presumed specific for NAD+. Fusion of TyrA domains with other catalytic domains is indicated within grey boxes (AroQ•TyrA, TyrA•AroF, HisHb•TyrA, and TyrA•AroQ•PheA•ACT) using the convention of a bullet to represent the interdomain area. The boxes overlap any relevant lineages. TyrA proteins having carboxy-terminal fusions with regulatory domains (TyrA•ACT and TyrA•REG) are also shown. The distance scale bar at the bottom left represents substitutions per site.
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Related In: Results  -  Collection

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Figure 2: Phylogenetic tree for trimmed core domains of selected members of the TyrA Superfamily. Acronyms used for the various organisms are given in alphabetical order in Table 2. (A more extensive listing that includes organisms not shown in Fig. 2 and which also is hyperlinked to all of the individual GenBank records is given in Table S1. A similar table that also includes compilation of known and predicted substrate specificities is maintained at AroPath [73]. Lineages possessing experimentally established TyrAa, TyrAp, TyrAc or TyrAc_Δ proteins are indicated by fill colors specified in the legend. Three specificity patterns for the pyridine nucleotide substrate are shown by line colors (see figure box). Although the cyanobacteria are depicted as having NADP+-specific TyrA proteins, some of them can also accept NAD, albeit to a lesser degree. All proteins having an aspartate residue homologous to D-32 of the E. coli NADTyrAc_Δ domain are presumed specific for NAD+. Fusion of TyrA domains with other catalytic domains is indicated within grey boxes (AroQ•TyrA, TyrA•AroF, HisHb•TyrA, and TyrA•AroQ•PheA•ACT) using the convention of a bullet to represent the interdomain area. The boxes overlap any relevant lineages. TyrA proteins having carboxy-terminal fusions with regulatory domains (TyrA•ACT and TyrA•REG) are also shown. The distance scale bar at the bottom left represents substitutions per site.
Mentions: Our evolutionary analysis is limited by the amount of information that can be managed in a single study, with the focus fixed upon the domain Bacteria (due to the relative density of genome representation for Bacteria in the public databases). However, in order to show where future expansion of the analysis might lead, the selection of TyrA proteins in Fig. 2 are from all three domains of life, i.e., Bacteria, Archaea, and Eukarya (lower eukaryotes and higher plants). For practicality of presentation, numerous orphan (i.e., without close relatives) TyrA sequences are not shown, and not all members of a given group are necessarily included. The main purposes of the radial tree shown in Fig. 2 are: (i) to illustrate that TyrA proteins of major phylogenetic groupings are generally congruent with 16S rRNA groupings and (ii) to convey a snapshot visualization of the overall complexity of the TyrA protein family from the vantage point of its varied substrate specificities as well as its multiple fusion partners.

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