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Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes.

Ragg H, Kumar A, Köster K, Bentele C, Wang Y, Frese MA, Prib N, Krüger O - BMC Evol. Biol. (2009)

Bottom Line: DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing.The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously.The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG upward arrowN, previously proposed to serve as intron insertion site.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biotechnology, Faculty of Technology and Center for Biotechnology, University of Bielefeld, D-33501 Bielefeld, Germany. hr@zellkult.techfak.uni-bielefeld.de

ABSTRACT

Background: Intron gains reportedly are very rare during evolution of vertebrates, and the mechanisms underlying their creation are largely unknown. Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes.

Results: Here we investigated intron dynamics in the serpin superfamily in lineages pre- and postdating the split of vertebrates. Multiple intron gains were detected in a group of ray-finned fishes, once the canonical groups of vertebrate serpins had been established. In two genes, co-occurrence of non-standard introns was observed, implying that intron gains in vertebrates may even happen concomitantly or in a rapidly consecutive manner. DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing.

Conclusion: Multiple intron acquisitions were identified in serpin genes of a lineage of ray-finned fishes, but not in any other vertebrates, suggesting that insertion rates for introns may be episodically increased. The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously. The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG upward arrowN, previously proposed to serve as intron insertion site. The association of intron gains in the serpin superfamily with a group of fishes that underwent genome compaction may indicate that DNA breakage/repair processes might foster intron birth.

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Intron gain in group V6 during diversification of ray-finned fishes. Ray-finned fishes contain up to three HSP47-related genes basically sharing the intron pattern of group V6 (intron positions marked in red). Non-canonical introns (positions marked in green) are exclusively found in some HSP47-related genes from Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes, but not in Danio rerio or other members of group V6. An intron located outside the serpin scaffold of X. tropicalis HSP47 is depicted in turquoise. Intron positions of human α1-antitrypsin (A1, group V2) are shown in yellow. The characteristic ER retention signal present at the C-terminus of all members of group V6 is printed in white on blue background. Sequence alignments and intron mapping were accomplished as described in the legend to Figure 2.
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Figure 3: Intron gain in group V6 during diversification of ray-finned fishes. Ray-finned fishes contain up to three HSP47-related genes basically sharing the intron pattern of group V6 (intron positions marked in red). Non-canonical introns (positions marked in green) are exclusively found in some HSP47-related genes from Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes, but not in Danio rerio or other members of group V6. An intron located outside the serpin scaffold of X. tropicalis HSP47 is depicted in turquoise. Intron positions of human α1-antitrypsin (A1, group V2) are shown in yellow. The characteristic ER retention signal present at the C-terminus of all members of group V6 is printed in white on blue background. Sequence alignments and intron mapping were accomplished as described in the legend to Figure 2.

Mentions: HCII, a serpin well known from various tetrapods, is a potent thrombin inhibitor in the presence of glycosaminoglycans (GAGs). Characteristic features of all HCII sequences are the highly conserved Arg/Lys-rich helix D that is involved in GAG binding and the acidic N-terminal extension that mediates GAG accelerated thrombin inhibition [25,26]. These features are also found in lamprey HCII (Additional file 1). The genes coding for angiotensinogen and HCII from lampreys each depict introns that interrupt the serpin scaffold at positions 192a, 282b, and 331c (standard repertoire of group V2; positions of group-specific standard introns are marked in red in all figures showing alignments). Beyond that, there are additional introns mapping to the N-terminus of HCII from P. marinus (see below). We also recognized a lamprey serpin exhibiting the exon-intron pattern of group V6 (introns at positions 192a, 225a, and 300c; Figure 3) as HSP47 orthologue. HSP47, a non-inhibitory serpin, is a specialized ER residing chaperone involved in folding and transport of procollagens [13,27]. A hallmark of all HSP47 proteins is the C-terminal ER retention/retrieval signal (HDEL/KDEL/RDEL). We conclude that angiotensinogen, HCII, and HSP47 are distinct members of the serpin superfamily that appeared early during vertebrate evolution. These proteins have persisted since at least 360 million years, assuming that the morphological concordance between a fossil lamprey from the Devonian period [28] and its present-day relatives is reflected on the molecular level.


Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes.

Ragg H, Kumar A, Köster K, Bentele C, Wang Y, Frese MA, Prib N, Krüger O - BMC Evol. Biol. (2009)

Intron gain in group V6 during diversification of ray-finned fishes. Ray-finned fishes contain up to three HSP47-related genes basically sharing the intron pattern of group V6 (intron positions marked in red). Non-canonical introns (positions marked in green) are exclusively found in some HSP47-related genes from Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes, but not in Danio rerio or other members of group V6. An intron located outside the serpin scaffold of X. tropicalis HSP47 is depicted in turquoise. Intron positions of human α1-antitrypsin (A1, group V2) are shown in yellow. The characteristic ER retention signal present at the C-terminus of all members of group V6 is printed in white on blue background. Sequence alignments and intron mapping were accomplished as described in the legend to Figure 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2746811&req=5

Figure 3: Intron gain in group V6 during diversification of ray-finned fishes. Ray-finned fishes contain up to three HSP47-related genes basically sharing the intron pattern of group V6 (intron positions marked in red). Non-canonical introns (positions marked in green) are exclusively found in some HSP47-related genes from Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes, but not in Danio rerio or other members of group V6. An intron located outside the serpin scaffold of X. tropicalis HSP47 is depicted in turquoise. Intron positions of human α1-antitrypsin (A1, group V2) are shown in yellow. The characteristic ER retention signal present at the C-terminus of all members of group V6 is printed in white on blue background. Sequence alignments and intron mapping were accomplished as described in the legend to Figure 2.
Mentions: HCII, a serpin well known from various tetrapods, is a potent thrombin inhibitor in the presence of glycosaminoglycans (GAGs). Characteristic features of all HCII sequences are the highly conserved Arg/Lys-rich helix D that is involved in GAG binding and the acidic N-terminal extension that mediates GAG accelerated thrombin inhibition [25,26]. These features are also found in lamprey HCII (Additional file 1). The genes coding for angiotensinogen and HCII from lampreys each depict introns that interrupt the serpin scaffold at positions 192a, 282b, and 331c (standard repertoire of group V2; positions of group-specific standard introns are marked in red in all figures showing alignments). Beyond that, there are additional introns mapping to the N-terminus of HCII from P. marinus (see below). We also recognized a lamprey serpin exhibiting the exon-intron pattern of group V6 (introns at positions 192a, 225a, and 300c; Figure 3) as HSP47 orthologue. HSP47, a non-inhibitory serpin, is a specialized ER residing chaperone involved in folding and transport of procollagens [13,27]. A hallmark of all HSP47 proteins is the C-terminal ER retention/retrieval signal (HDEL/KDEL/RDEL). We conclude that angiotensinogen, HCII, and HSP47 are distinct members of the serpin superfamily that appeared early during vertebrate evolution. These proteins have persisted since at least 360 million years, assuming that the morphological concordance between a fossil lamprey from the Devonian period [28] and its present-day relatives is reflected on the molecular level.

Bottom Line: DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing.The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously.The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG upward arrowN, previously proposed to serve as intron insertion site.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biotechnology, Faculty of Technology and Center for Biotechnology, University of Bielefeld, D-33501 Bielefeld, Germany. hr@zellkult.techfak.uni-bielefeld.de

ABSTRACT

Background: Intron gains reportedly are very rare during evolution of vertebrates, and the mechanisms underlying their creation are largely unknown. Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes.

Results: Here we investigated intron dynamics in the serpin superfamily in lineages pre- and postdating the split of vertebrates. Multiple intron gains were detected in a group of ray-finned fishes, once the canonical groups of vertebrate serpins had been established. In two genes, co-occurrence of non-standard introns was observed, implying that intron gains in vertebrates may even happen concomitantly or in a rapidly consecutive manner. DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing.

Conclusion: Multiple intron acquisitions were identified in serpin genes of a lineage of ray-finned fishes, but not in any other vertebrates, suggesting that insertion rates for introns may be episodically increased. The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously. The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG upward arrowN, previously proposed to serve as intron insertion site. The association of intron gains in the serpin superfamily with a group of fishes that underwent genome compaction may indicate that DNA breakage/repair processes might foster intron birth.

Show MeSH