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Integrative view of α2,3-sialyltransferases (ST3Gal) molecular and functional evolution in deuterostomes: significance of lineage-specific losses.

Petit D, Teppa E, Mir AM, Vicogne D, Thisse C, Thisse B, Filloux C, Harduin-Lepers A - Mol. Biol. Evol. (2014)

Bottom Line: Toward this aim, spatiotemporal distribution of st3gal genes was analyzed in zebrafish and bovine tissues.In addition, molecular evolutionary analyses using specificity determining position and coevolved amino acid predictions led to the identification of amino acid residues with potential implication in functional divergence of vertebrate ST3Gal.We propose a detailed scenario of the evolutionary relationships of st3gal genes coupled to a conceptual framework of the evolution of ST3Gal functions.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR 1061, Unité Génétique Moléculaire Animale, F-87060 Limoges Cedex, France Université de Limoges, UMR 1061, Unité Génétique Moléculaire Animale, 123 avenue Albert Thomas, F-87060 Limoges Cedex, France.

No MeSH data available.


Related in: MedlinePlus

(A) Conservation of amino acid stretches in the vertebrate ST3Gal sequences evidenced by automatic conserved sequence searches. We assessed conservation of the 382 amino acid positions selected from the vertebrate ST3Gal sequences considered for phylogeny analyses (see tables S1 and S2, Supplementary Material online) using an automatic search of consensus sequences described in Materials and Method. For each subfamily, the consensus sequences were aligned with the one generated by MEGA 5.0. The resulting alignment is used to detect those positions called SDP that are conserved within groups of related proteins that perform the same function (specificity groups). SDP type I is variable in one group and conserved in the others, whereas type II positions show different conserved amino acids among the various groups of sequences. Amino acids residues belonging to conserved peptide sequences are shown. Amino acid positions with a yellow background identify conserved amino acid for the α2,3-sialyltransferase-related sequences of the GR1 group, with a green background those of the GR3 (especially the ST3Gal V–VII), with an orange background, those of the GR2, and with a blue background, those of the GR2 and GR3. The sialylmotifs L, S, III, and VS are indicated in black background, and the specific motifs to ST3Gal family –a-, -b- and –c-, in gray background. The positions are numbered from the beginning of the stem, excluding the N-terminus and the transmembrane domain. SDP prediction for GR1, GR2, and GR3 groups. (B) Representation of five SDPs located nearby the active site is represented in the reference structure (PDB: 2WNB). The modeled lid domain is shown in yellow, donor and acceptor substrates are shown in black stick representation, SDPs are shown in red or blue stick, the label indicates the conserved amino acid and the corresponding group (i.e., near CMP a W is conserved in GR1 and it is represented in red, whereas a Y is conserved in GR2 and GR3 at the same position, which is represented in blue).When there is no conserved residue in a group, the position is labeled as Δ in black. (C) SDP in surface representation of the reference structure (PDB: 2WNB). The modeled lid domain is highlighted in yellow, SDP predicted in red, the donor and acceptor substrate are shown in black. Note that the lid domain flexibility can alter the binding site of both substrates, and also the amino acid change in the SDP. (D) Table summarizing SDPs information. First column indicates the corresponding position in the reference structure (PDB: 2WNB); second column the position in the MSA, the third the most conserved residues for each group, the * indicates variable position; in the last column is entered a description that can be related to the function of the position.
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msu395-F5: (A) Conservation of amino acid stretches in the vertebrate ST3Gal sequences evidenced by automatic conserved sequence searches. We assessed conservation of the 382 amino acid positions selected from the vertebrate ST3Gal sequences considered for phylogeny analyses (see tables S1 and S2, Supplementary Material online) using an automatic search of consensus sequences described in Materials and Method. For each subfamily, the consensus sequences were aligned with the one generated by MEGA 5.0. The resulting alignment is used to detect those positions called SDP that are conserved within groups of related proteins that perform the same function (specificity groups). SDP type I is variable in one group and conserved in the others, whereas type II positions show different conserved amino acids among the various groups of sequences. Amino acids residues belonging to conserved peptide sequences are shown. Amino acid positions with a yellow background identify conserved amino acid for the α2,3-sialyltransferase-related sequences of the GR1 group, with a green background those of the GR3 (especially the ST3Gal V–VII), with an orange background, those of the GR2, and with a blue background, those of the GR2 and GR3. The sialylmotifs L, S, III, and VS are indicated in black background, and the specific motifs to ST3Gal family –a-, -b- and –c-, in gray background. The positions are numbered from the beginning of the stem, excluding the N-terminus and the transmembrane domain. SDP prediction for GR1, GR2, and GR3 groups. (B) Representation of five SDPs located nearby the active site is represented in the reference structure (PDB: 2WNB). The modeled lid domain is shown in yellow, donor and acceptor substrates are shown in black stick representation, SDPs are shown in red or blue stick, the label indicates the conserved amino acid and the corresponding group (i.e., near CMP a W is conserved in GR1 and it is represented in red, whereas a Y is conserved in GR2 and GR3 at the same position, which is represented in blue).When there is no conserved residue in a group, the position is labeled as Δ in black. (C) SDP in surface representation of the reference structure (PDB: 2WNB). The modeled lid domain is highlighted in yellow, SDP predicted in red, the donor and acceptor substrate are shown in black. Note that the lid domain flexibility can alter the binding site of both substrates, and also the amino acid change in the SDP. (D) Table summarizing SDPs information. First column indicates the corresponding position in the reference structure (PDB: 2WNB); second column the position in the MSA, the third the most conserved residues for each group, the * indicates variable position; in the last column is entered a description that can be related to the function of the position.

Mentions: In an attempt to shed light on the molecular mechanisms underpinning vertebrate ST3Gal functional divergence, we further studied conserved and coevolving amino acids in ST3Gal sequences. Indeed, changes in conservation degree in a particular amino acid position may reflect functional innovation after gene duplication, because one copy evolves under relaxed constraints, which allows it to accumulate changes and develop new functions and specificities. Traditionally, two basic types of functional divergence sites have been distinguished according to Gu (2001) (see Materials and Methods). Our bioinformatic program retrieved consensus sequences in the stem region for each vertebrate ST3Gal subfamily, but nearly none for groups of subfamilies (fig. 5A). In contrast, most of the catalytic domain was retrieved as a series of consensus sequences common to groups of subfamilies. From this initial analysis, the GR1 group was clearly apart from the two remaining GR2 and GR3 groups as illustrated by the presence of about 67 type I sites highlighting different evolutionary rates (fig. 5A).Fig. 5.


Integrative view of α2,3-sialyltransferases (ST3Gal) molecular and functional evolution in deuterostomes: significance of lineage-specific losses.

Petit D, Teppa E, Mir AM, Vicogne D, Thisse C, Thisse B, Filloux C, Harduin-Lepers A - Mol. Biol. Evol. (2014)

(A) Conservation of amino acid stretches in the vertebrate ST3Gal sequences evidenced by automatic conserved sequence searches. We assessed conservation of the 382 amino acid positions selected from the vertebrate ST3Gal sequences considered for phylogeny analyses (see tables S1 and S2, Supplementary Material online) using an automatic search of consensus sequences described in Materials and Method. For each subfamily, the consensus sequences were aligned with the one generated by MEGA 5.0. The resulting alignment is used to detect those positions called SDP that are conserved within groups of related proteins that perform the same function (specificity groups). SDP type I is variable in one group and conserved in the others, whereas type II positions show different conserved amino acids among the various groups of sequences. Amino acids residues belonging to conserved peptide sequences are shown. Amino acid positions with a yellow background identify conserved amino acid for the α2,3-sialyltransferase-related sequences of the GR1 group, with a green background those of the GR3 (especially the ST3Gal V–VII), with an orange background, those of the GR2, and with a blue background, those of the GR2 and GR3. The sialylmotifs L, S, III, and VS are indicated in black background, and the specific motifs to ST3Gal family –a-, -b- and –c-, in gray background. The positions are numbered from the beginning of the stem, excluding the N-terminus and the transmembrane domain. SDP prediction for GR1, GR2, and GR3 groups. (B) Representation of five SDPs located nearby the active site is represented in the reference structure (PDB: 2WNB). The modeled lid domain is shown in yellow, donor and acceptor substrates are shown in black stick representation, SDPs are shown in red or blue stick, the label indicates the conserved amino acid and the corresponding group (i.e., near CMP a W is conserved in GR1 and it is represented in red, whereas a Y is conserved in GR2 and GR3 at the same position, which is represented in blue).When there is no conserved residue in a group, the position is labeled as Δ in black. (C) SDP in surface representation of the reference structure (PDB: 2WNB). The modeled lid domain is highlighted in yellow, SDP predicted in red, the donor and acceptor substrate are shown in black. Note that the lid domain flexibility can alter the binding site of both substrates, and also the amino acid change in the SDP. (D) Table summarizing SDPs information. First column indicates the corresponding position in the reference structure (PDB: 2WNB); second column the position in the MSA, the third the most conserved residues for each group, the * indicates variable position; in the last column is entered a description that can be related to the function of the position.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4379398&req=5

msu395-F5: (A) Conservation of amino acid stretches in the vertebrate ST3Gal sequences evidenced by automatic conserved sequence searches. We assessed conservation of the 382 amino acid positions selected from the vertebrate ST3Gal sequences considered for phylogeny analyses (see tables S1 and S2, Supplementary Material online) using an automatic search of consensus sequences described in Materials and Method. For each subfamily, the consensus sequences were aligned with the one generated by MEGA 5.0. The resulting alignment is used to detect those positions called SDP that are conserved within groups of related proteins that perform the same function (specificity groups). SDP type I is variable in one group and conserved in the others, whereas type II positions show different conserved amino acids among the various groups of sequences. Amino acids residues belonging to conserved peptide sequences are shown. Amino acid positions with a yellow background identify conserved amino acid for the α2,3-sialyltransferase-related sequences of the GR1 group, with a green background those of the GR3 (especially the ST3Gal V–VII), with an orange background, those of the GR2, and with a blue background, those of the GR2 and GR3. The sialylmotifs L, S, III, and VS are indicated in black background, and the specific motifs to ST3Gal family –a-, -b- and –c-, in gray background. The positions are numbered from the beginning of the stem, excluding the N-terminus and the transmembrane domain. SDP prediction for GR1, GR2, and GR3 groups. (B) Representation of five SDPs located nearby the active site is represented in the reference structure (PDB: 2WNB). The modeled lid domain is shown in yellow, donor and acceptor substrates are shown in black stick representation, SDPs are shown in red or blue stick, the label indicates the conserved amino acid and the corresponding group (i.e., near CMP a W is conserved in GR1 and it is represented in red, whereas a Y is conserved in GR2 and GR3 at the same position, which is represented in blue).When there is no conserved residue in a group, the position is labeled as Δ in black. (C) SDP in surface representation of the reference structure (PDB: 2WNB). The modeled lid domain is highlighted in yellow, SDP predicted in red, the donor and acceptor substrate are shown in black. Note that the lid domain flexibility can alter the binding site of both substrates, and also the amino acid change in the SDP. (D) Table summarizing SDPs information. First column indicates the corresponding position in the reference structure (PDB: 2WNB); second column the position in the MSA, the third the most conserved residues for each group, the * indicates variable position; in the last column is entered a description that can be related to the function of the position.
Mentions: In an attempt to shed light on the molecular mechanisms underpinning vertebrate ST3Gal functional divergence, we further studied conserved and coevolving amino acids in ST3Gal sequences. Indeed, changes in conservation degree in a particular amino acid position may reflect functional innovation after gene duplication, because one copy evolves under relaxed constraints, which allows it to accumulate changes and develop new functions and specificities. Traditionally, two basic types of functional divergence sites have been distinguished according to Gu (2001) (see Materials and Methods). Our bioinformatic program retrieved consensus sequences in the stem region for each vertebrate ST3Gal subfamily, but nearly none for groups of subfamilies (fig. 5A). In contrast, most of the catalytic domain was retrieved as a series of consensus sequences common to groups of subfamilies. From this initial analysis, the GR1 group was clearly apart from the two remaining GR2 and GR3 groups as illustrated by the presence of about 67 type I sites highlighting different evolutionary rates (fig. 5A).Fig. 5.

Bottom Line: Toward this aim, spatiotemporal distribution of st3gal genes was analyzed in zebrafish and bovine tissues.In addition, molecular evolutionary analyses using specificity determining position and coevolved amino acid predictions led to the identification of amino acid residues with potential implication in functional divergence of vertebrate ST3Gal.We propose a detailed scenario of the evolutionary relationships of st3gal genes coupled to a conceptual framework of the evolution of ST3Gal functions.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR 1061, Unité Génétique Moléculaire Animale, F-87060 Limoges Cedex, France Université de Limoges, UMR 1061, Unité Génétique Moléculaire Animale, 123 avenue Albert Thomas, F-87060 Limoges Cedex, France.

No MeSH data available.


Related in: MedlinePlus