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The evolution of pepsinogen C genes in vertebrates: duplication, loss and functional diversification.

Castro LF, Lopes-Marques M, Gonçalves O, Wilson JM - PLoS ONE (2012)

Bottom Line: A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga).We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation.We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes.

View Article: PubMed Central - PubMed

Affiliation: CIMAR Associate Laboratory, CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, UPorto-University of Porto, Porto, Portugal. filipe.castro@ciimar.up.pt

ABSTRACT

Background: Aspartic proteases comprise a large group of enzymes involved in peptide proteolysis. This collection includes prominent enzymes globally categorized as pepsins, which are derived from pepsinogen precursors. Pepsins are involved in gastric digestion, a hallmark of vertebrate physiology. An important member among the pepsinogens is pepsinogen C (Pgc). A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga). Although gene sequences with similarity to Pgc have been described in some vertebrate groups, no exhaustive evolutionary framework has been considered so far.

Methodology/principal findings: By combining phylogenetics and genomic analysis, we find an unexpected Pgc diversity in the vertebrate sub-phylum. We were able to reconstruct gene duplication timings relative to the divergence of major vertebrate clades. Before tetrapod divergence, a single Pgc gene tandemly expanded to produce two gene lineages (Pgbc and Pgc2). These have been differentially retained in various classes. Accordingly, we find Pgc2 in sauropsids, amphibians and marsupials, but not in eutherian mammals. Pgbc was retained in amphibians, but duplicated in the ancestor of amniotes giving rise to Pgb and Pgc1. The latter was retained in mammals and probably in reptiles and marsupials but not in birds. Pgb was kept in all of the amniote clade with independent episodes of loss in some mammalian species. Lineage specific expansions of Pgc2 and Pgbc have also occurred in marsupials and amphibians respectively. We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation.

Conclusions: We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes. We hypothesize that gene expansion lead to functional divergence in tetrapods, coincident with the invasion of terrestrial habitats.

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Pgc loci are conserved in teleost species, and indicate gene loss in some lineages.Gac – G. aculeatus, Tru- T. rubripes, Tni- T. nigroviridis, Ola- O. latipes and Dre- D. rerio. Numbers are distances between genes in Kb.
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pone-0032852-g004: Pgc loci are conserved in teleost species, and indicate gene loss in some lineages.Gac – G. aculeatus, Tru- T. rubripes, Tni- T. nigroviridis, Ola- O. latipes and Dre- D. rerio. Numbers are distances between genes in Kb.

Mentions: In contrast to tetrapods a single Pgc gene sequence has been described in various teleost species [9], a conclusion we now extent to stickleback. In this species, we find a single Pgc gene localizing to Group XIX (Fig. 4). A close inspection of the gene families flanking GacPgc shows no evidence of syntenic conservation in comparison to the tetrapod Pgc locus. We find for example that the stickleback orthologues of Frs3 and Tfeb which outflank the Pgc gene cluster in tetrapods localize to Sca_27 in stickleback (not shown). Thus, Pgc has been apparently translocated from its original position in either tetrapods or teleosts and is of no evolutionary meaning. Mapping information from cartilaginous fish and pre-3R teleost species may provide insightful information on this issue. Except for the stickleback, we found no Pgc-like sequence in other teleost species with full genome sequences. To confirm the loss of Pgc sequences we analysed the composition of the GacPgc locus in zebrafish, medaka, pufferfish, and green pufferfish (Fig. 4). This approach confirms that neither of these species has a Pgc sequence in the genome (nor evidence for pseudogenization), despite the conservation of locus composition and organization.


The evolution of pepsinogen C genes in vertebrates: duplication, loss and functional diversification.

Castro LF, Lopes-Marques M, Gonçalves O, Wilson JM - PLoS ONE (2012)

Pgc loci are conserved in teleost species, and indicate gene loss in some lineages.Gac – G. aculeatus, Tru- T. rubripes, Tni- T. nigroviridis, Ola- O. latipes and Dre- D. rerio. Numbers are distances between genes in Kb.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3298455&req=5

pone-0032852-g004: Pgc loci are conserved in teleost species, and indicate gene loss in some lineages.Gac – G. aculeatus, Tru- T. rubripes, Tni- T. nigroviridis, Ola- O. latipes and Dre- D. rerio. Numbers are distances between genes in Kb.
Mentions: In contrast to tetrapods a single Pgc gene sequence has been described in various teleost species [9], a conclusion we now extent to stickleback. In this species, we find a single Pgc gene localizing to Group XIX (Fig. 4). A close inspection of the gene families flanking GacPgc shows no evidence of syntenic conservation in comparison to the tetrapod Pgc locus. We find for example that the stickleback orthologues of Frs3 and Tfeb which outflank the Pgc gene cluster in tetrapods localize to Sca_27 in stickleback (not shown). Thus, Pgc has been apparently translocated from its original position in either tetrapods or teleosts and is of no evolutionary meaning. Mapping information from cartilaginous fish and pre-3R teleost species may provide insightful information on this issue. Except for the stickleback, we found no Pgc-like sequence in other teleost species with full genome sequences. To confirm the loss of Pgc sequences we analysed the composition of the GacPgc locus in zebrafish, medaka, pufferfish, and green pufferfish (Fig. 4). This approach confirms that neither of these species has a Pgc sequence in the genome (nor evidence for pseudogenization), despite the conservation of locus composition and organization.

Bottom Line: A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga).We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation.We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes.

View Article: PubMed Central - PubMed

Affiliation: CIMAR Associate Laboratory, CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, UPorto-University of Porto, Porto, Portugal. filipe.castro@ciimar.up.pt

ABSTRACT

Background: Aspartic proteases comprise a large group of enzymes involved in peptide proteolysis. This collection includes prominent enzymes globally categorized as pepsins, which are derived from pepsinogen precursors. Pepsins are involved in gastric digestion, a hallmark of vertebrate physiology. An important member among the pepsinogens is pepsinogen C (Pgc). A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga). Although gene sequences with similarity to Pgc have been described in some vertebrate groups, no exhaustive evolutionary framework has been considered so far.

Methodology/principal findings: By combining phylogenetics and genomic analysis, we find an unexpected Pgc diversity in the vertebrate sub-phylum. We were able to reconstruct gene duplication timings relative to the divergence of major vertebrate clades. Before tetrapod divergence, a single Pgc gene tandemly expanded to produce two gene lineages (Pgbc and Pgc2). These have been differentially retained in various classes. Accordingly, we find Pgc2 in sauropsids, amphibians and marsupials, but not in eutherian mammals. Pgbc was retained in amphibians, but duplicated in the ancestor of amniotes giving rise to Pgb and Pgc1. The latter was retained in mammals and probably in reptiles and marsupials but not in birds. Pgb was kept in all of the amniote clade with independent episodes of loss in some mammalian species. Lineage specific expansions of Pgc2 and Pgbc have also occurred in marsupials and amphibians respectively. We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation.

Conclusions: We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes. We hypothesize that gene expansion lead to functional divergence in tetrapods, coincident with the invasion of terrestrial habitats.

Show MeSH