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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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Context of gene organization for tyrA, profiled against the 16S rRNA tree of the domain Bacteria. pheA, hisHb, tyrA, and aroF are color coded. Lineages typified by complete dispersal of aromatic-pathway genes are indicated by "GENE DISPERSAL". Gmet refers to Geobacter metallireducens; Dace refers to Desulfuromonas acetoxidans; and Ddes refers to Desulfovibrio desulfuricans. Consensus gene organizations are shown for the alpha and beta divisions of the Proteobacteria. The gamma division is subdivided to yield consensus gene organizations for the upper- and lower-gamma (enteric lineage) organisms. Genes that are adjacent and share a common transcriptional direction appear to reside in operons (or supraoperons). Any white spacing indicates substantial separation of the gene clusters shown in the genome. Genes of special interest are color coded, other genes of aromatic biosynthesis are shown in gray and all other genes are shown in white.
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Figure 5: Context of gene organization for tyrA, profiled against the 16S rRNA tree of the domain Bacteria. pheA, hisHb, tyrA, and aroF are color coded. Lineages typified by complete dispersal of aromatic-pathway genes are indicated by "GENE DISPERSAL". Gmet refers to Geobacter metallireducens; Dace refers to Desulfuromonas acetoxidans; and Ddes refers to Desulfovibrio desulfuricans. Consensus gene organizations are shown for the alpha and beta divisions of the Proteobacteria. The gamma division is subdivided to yield consensus gene organizations for the upper- and lower-gamma (enteric lineage) organisms. Genes that are adjacent and share a common transcriptional direction appear to reside in operons (or supraoperons). Any white spacing indicates substantial separation of the gene clusters shown in the genome. Genes of special interest are color coded, other genes of aromatic biosynthesis are shown in gray and all other genes are shown in white.

Mentions: The domain Bacteria is now represented by a collection of sequenced genomes that is progressively approaching the genomic densities needed for meaningful analysis. Figure 5 provides a visual sense of the frequency with which tyrA is closely positioned with other genes of aromatic biosynthesis, as well as the underlying patterns of overall synteny. These patterns are unstable, and yet persistent traces of synteny can be seen where genomic representation is sufficiently dense. The four genes of particular emphasis in this paper are color coded. Other genes that are engaged in aromatic biosynthesis are colored grey, and any other genes are white. At a very deep level of phylogenetic branching, Thermotoga exhibits a tyrA gene flanked by seven genes encoding all of the common steps of aromatic biosynthesis (two of them being fused). Since closely related genomes are not yet available here, we cannot judge whether these genes came together recently or whether an ancient pattern of synteny has been retained. Although tyrA is not linked to any functionally relevant genes in Aquifex, representing another point of deep phylogenetic branching, this does not necessarily mean that tyrA was not already generally associated with other aromatic-pathway genes at an early time. For reasons that are totally mysterious, certain scattered lineages exhibit a total lack of operon organization for aromatic-pathway genes (and indeed for most other biosynthetic pathways, such as that for histidine biosynthesis). These lineages (Fig. 5) include, besides Aquifex, those of Deinococcus, the actinomycetes, the cyanobacteria, and Chlorobium. Except for the actinomycetes, this phenomenon of total gene dispersal also applies to genes of tryptophan biosynthesis [7,8].


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

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

Context of gene organization for tyrA, profiled against the 16S rRNA tree of the domain Bacteria. pheA, hisHb, tyrA, and aroF are color coded. Lineages typified by complete dispersal of aromatic-pathway genes are indicated by "GENE DISPERSAL". Gmet refers to Geobacter metallireducens; Dace refers to Desulfuromonas acetoxidans; and Ddes refers to Desulfovibrio desulfuricans. Consensus gene organizations are shown for the alpha and beta divisions of the Proteobacteria. The gamma division is subdivided to yield consensus gene organizations for the upper- and lower-gamma (enteric lineage) organisms. Genes that are adjacent and share a common transcriptional direction appear to reside in operons (or supraoperons). Any white spacing indicates substantial separation of the gene clusters shown in the genome. Genes of special interest are color coded, other genes of aromatic biosynthesis are shown in gray and all other genes are shown in white.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Context of gene organization for tyrA, profiled against the 16S rRNA tree of the domain Bacteria. pheA, hisHb, tyrA, and aroF are color coded. Lineages typified by complete dispersal of aromatic-pathway genes are indicated by "GENE DISPERSAL". Gmet refers to Geobacter metallireducens; Dace refers to Desulfuromonas acetoxidans; and Ddes refers to Desulfovibrio desulfuricans. Consensus gene organizations are shown for the alpha and beta divisions of the Proteobacteria. The gamma division is subdivided to yield consensus gene organizations for the upper- and lower-gamma (enteric lineage) organisms. Genes that are adjacent and share a common transcriptional direction appear to reside in operons (or supraoperons). Any white spacing indicates substantial separation of the gene clusters shown in the genome. Genes of special interest are color coded, other genes of aromatic biosynthesis are shown in gray and all other genes are shown in white.
Mentions: The domain Bacteria is now represented by a collection of sequenced genomes that is progressively approaching the genomic densities needed for meaningful analysis. Figure 5 provides a visual sense of the frequency with which tyrA is closely positioned with other genes of aromatic biosynthesis, as well as the underlying patterns of overall synteny. These patterns are unstable, and yet persistent traces of synteny can be seen where genomic representation is sufficiently dense. The four genes of particular emphasis in this paper are color coded. Other genes that are engaged in aromatic biosynthesis are colored grey, and any other genes are white. At a very deep level of phylogenetic branching, Thermotoga exhibits a tyrA gene flanked by seven genes encoding all of the common steps of aromatic biosynthesis (two of them being fused). Since closely related genomes are not yet available here, we cannot judge whether these genes came together recently or whether an ancient pattern of synteny has been retained. Although tyrA is not linked to any functionally relevant genes in Aquifex, representing another point of deep phylogenetic branching, this does not necessarily mean that tyrA was not already generally associated with other aromatic-pathway genes at an early time. For reasons that are totally mysterious, certain scattered lineages exhibit a total lack of operon organization for aromatic-pathway genes (and indeed for most other biosynthetic pathways, such as that for histidine biosynthesis). These lineages (Fig. 5) include, besides Aquifex, those of Deinococcus, the actinomycetes, the cyanobacteria, and Chlorobium. Except for the actinomycetes, this phenomenon of total gene dispersal also applies to genes of tryptophan biosynthesis [7,8].

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