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Structural and functional diversification in the teleost S100 family of calcium-binding proteins.

Kraemer AM, Saraiva LR, Korsching SI - BMC Evol. Biol. (2008)

Bottom Line: Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses.Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes.Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Genetics, University of Cologne, Zuelpicher Strasse 47, 50674 Cologne, Germany. a.kraemer@gmx.com

ABSTRACT

Background: Among the EF-Hand calcium-binding proteins the subgroup of S100 proteins constitute a large family with numerous and diverse functions in calcium-mediated signaling. The evolutionary origin of this family is still uncertain and most studies have examined mammalian family members.

Results: We have performed an extensive search in several teleost genomes to establish the s100 gene family in fish. We report that the teleost S100 repertoire comprises fourteen different subfamilies which show remarkable similarity across six divergent teleost species. Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses. Eight of the fourteen S100 subfamilies are unique for teleosts, while six are shared with mammalian species and three of those even with cartilaginous fish. Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes. All teleost s100 genes show the expected structural features and are subject to strong negative selection. Many aspects of the genomic arrangement and location of mammalian s100 genes are retained in the teleost s100 gene family, including a completely conserved intron/exon border between the two EF hands. Zebrafish s100 genes exhibit highly specific and characteristic expression patterns, showing both redundancy and divergence in their cellular expression. In larval tissue expression is often restricted to specific cell types like keratinocytes, hair cells, ionocytes and olfactory receptor neurons as demonstrated by in situ hybridization.

Conclusion: The origin of the S100 family predates at least the segregation of jawed from jawless fish and some extant family members predate the divergence of bony from cartilaginous fish. Despite a complex pattern of gene gains and losses the total repertoire size is remarkably constant between species. On the expression level the teleost S100 proteins can serve as precise markers for several different cell types. At least some of their functions may be related to those of their counterparts in mammals. Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

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Amino acid sequence conservation in the fish s100 gene repertoire. Conservation is displayed as a sequence logo. In this representation, the relative frequency with which an amino acid appears at a given position is reflected by the height of its one-letter amino acid code in the logo, with the total height at a given position proportional to the level of sequence conservation. The regions corresponding to the Helices (H), the S100 EF Hand Calcium-binding domain, the Hinge and the Calcium-binding domain of the canonical EF Hand are numbered and indicated. Sequence alignments were manually edited (for details see Methods section).
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Figure 4: Amino acid sequence conservation in the fish s100 gene repertoire. Conservation is displayed as a sequence logo. In this representation, the relative frequency with which an amino acid appears at a given position is reflected by the height of its one-letter amino acid code in the logo, with the total height at a given position proportional to the level of sequence conservation. The regions corresponding to the Helices (H), the S100 EF Hand Calcium-binding domain, the Hinge and the Calcium-binding domain of the canonical EF Hand are numbered and indicated. Sequence alignments were manually edited (for details see Methods section).

Mentions: The evolutionary distances between ortholog amino acid sequences range between 0.11 and 0.82 (Figure 3B, Additional File 3), whereas paralog distances range between 0.97 and 1.18 (Additional File 3). Because of this high heterogeneity among the S100 family and to obtain a second line of evidence in order to classify these genes reliably as members of the S100 family, we next examined the degree of conservation of the fish and mammalian genes. For that purpose, sequence logos from the amino acid alignments of either the fish or mammalian S100 proteins alone and of a combination of all the S100 proteins were created and used for a comparative analysis (Figure 4 and data not shown). All three sequence logos were very similar and showed the same general conservation pattern. The previously described typical structure of the mammalian S100 proteins formed by four helices (Helix I-IV) separated by a S100 EF hand calcium-binding domain, a hinge and a canonical EF hand calcium-binding domain [1] is conserved among the fish S100 proteins. A high number of conserved residues and signature motifs in defined positions of the sequence were identified in the teleost S100 proteins (Figure 4) and found to be conserved also among fish and tetrapods, consistent with the origin of the S100 family well before the actinopterygian/sarcopterygian split (Figure 2). These residues are located mainly in the helix domains and the calcium-binding regions, especially in the canonical EF hand. This result is in accordance with a recent study that classifies this region as phylogenetically older than the S100 EF hand domains [15]. In contrast, the hinge region and the C-terminus seem to be regions where there is more space for sequence variability (Figure 4). This is in accordance with the observation in mammalian S100 proteins that the selectivity in target binding is mainly assured by the hinge region and the C-terminal tail [2,7], i.e. in these regions a larger divergence is expected at least between paralogs.


Structural and functional diversification in the teleost S100 family of calcium-binding proteins.

Kraemer AM, Saraiva LR, Korsching SI - BMC Evol. Biol. (2008)

Amino acid sequence conservation in the fish s100 gene repertoire. Conservation is displayed as a sequence logo. In this representation, the relative frequency with which an amino acid appears at a given position is reflected by the height of its one-letter amino acid code in the logo, with the total height at a given position proportional to the level of sequence conservation. The regions corresponding to the Helices (H), the S100 EF Hand Calcium-binding domain, the Hinge and the Calcium-binding domain of the canonical EF Hand are numbered and indicated. Sequence alignments were manually edited (for details see Methods section).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266712&req=5

Figure 4: Amino acid sequence conservation in the fish s100 gene repertoire. Conservation is displayed as a sequence logo. In this representation, the relative frequency with which an amino acid appears at a given position is reflected by the height of its one-letter amino acid code in the logo, with the total height at a given position proportional to the level of sequence conservation. The regions corresponding to the Helices (H), the S100 EF Hand Calcium-binding domain, the Hinge and the Calcium-binding domain of the canonical EF Hand are numbered and indicated. Sequence alignments were manually edited (for details see Methods section).
Mentions: The evolutionary distances between ortholog amino acid sequences range between 0.11 and 0.82 (Figure 3B, Additional File 3), whereas paralog distances range between 0.97 and 1.18 (Additional File 3). Because of this high heterogeneity among the S100 family and to obtain a second line of evidence in order to classify these genes reliably as members of the S100 family, we next examined the degree of conservation of the fish and mammalian genes. For that purpose, sequence logos from the amino acid alignments of either the fish or mammalian S100 proteins alone and of a combination of all the S100 proteins were created and used for a comparative analysis (Figure 4 and data not shown). All three sequence logos were very similar and showed the same general conservation pattern. The previously described typical structure of the mammalian S100 proteins formed by four helices (Helix I-IV) separated by a S100 EF hand calcium-binding domain, a hinge and a canonical EF hand calcium-binding domain [1] is conserved among the fish S100 proteins. A high number of conserved residues and signature motifs in defined positions of the sequence were identified in the teleost S100 proteins (Figure 4) and found to be conserved also among fish and tetrapods, consistent with the origin of the S100 family well before the actinopterygian/sarcopterygian split (Figure 2). These residues are located mainly in the helix domains and the calcium-binding regions, especially in the canonical EF hand. This result is in accordance with a recent study that classifies this region as phylogenetically older than the S100 EF hand domains [15]. In contrast, the hinge region and the C-terminus seem to be regions where there is more space for sequence variability (Figure 4). This is in accordance with the observation in mammalian S100 proteins that the selectivity in target binding is mainly assured by the hinge region and the C-terminal tail [2,7], i.e. in these regions a larger divergence is expected at least between paralogs.

Bottom Line: Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses.Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes.Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Genetics, University of Cologne, Zuelpicher Strasse 47, 50674 Cologne, Germany. a.kraemer@gmx.com

ABSTRACT

Background: Among the EF-Hand calcium-binding proteins the subgroup of S100 proteins constitute a large family with numerous and diverse functions in calcium-mediated signaling. The evolutionary origin of this family is still uncertain and most studies have examined mammalian family members.

Results: We have performed an extensive search in several teleost genomes to establish the s100 gene family in fish. We report that the teleost S100 repertoire comprises fourteen different subfamilies which show remarkable similarity across six divergent teleost species. Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses. Eight of the fourteen S100 subfamilies are unique for teleosts, while six are shared with mammalian species and three of those even with cartilaginous fish. Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes. All teleost s100 genes show the expected structural features and are subject to strong negative selection. Many aspects of the genomic arrangement and location of mammalian s100 genes are retained in the teleost s100 gene family, including a completely conserved intron/exon border between the two EF hands. Zebrafish s100 genes exhibit highly specific and characteristic expression patterns, showing both redundancy and divergence in their cellular expression. In larval tissue expression is often restricted to specific cell types like keratinocytes, hair cells, ionocytes and olfactory receptor neurons as demonstrated by in situ hybridization.

Conclusion: The origin of the S100 family predates at least the segregation of jawed from jawless fish and some extant family members predate the divergence of bony from cartilaginous fish. Despite a complex pattern of gene gains and losses the total repertoire size is remarkably constant between species. On the expression level the teleost S100 proteins can serve as precise markers for several different cell types. At least some of their functions may be related to those of their counterparts in mammals. Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

Show MeSH