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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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Proposed evolutionary history and duplication timings of the Pgc gene family in vertebrates.Numbers inside each box denotes gene numbers.
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pone-0032852-g005: Proposed evolutionary history and duplication timings of the Pgc gene family in vertebrates.Numbers inside each box denotes gene numbers.

Mentions: Here we analyse the evolutionary history of a gene family involved in the vertebrate gastric function, the Pgc, to find that extensive gene duplication and loss occurred in vertebrate classes. Our research begun by inquiring a long held premise that Pgc is a single copy gene family in vertebrate species [3], [9], [10], [11]. By taking an exhaustive search into various vertebrate genomes, we demonstrate that significant discrepancy in Pgc complements exists between species. For example, we find no Pgc-like gene in some teleost species (e.g. medaka), while up to five genes are found in the opossum and the western clawed frog. We next undertook a combination of phylogenetics and chromosomal gene location (and their neighbouring gene families) to reconstruct gene duplication timings and processes, relative to the divergence of major vertebrate classes. Our analysis supports an evolutionary scenario where tandem gene duplication and gene loss have dynamically taken place in the tetrapod lineage (Fig. 5). Consequently, we introduce a new gene nomenclature that incorporates the phylogenetic findings. Before the diversification of tetrapods, a gene duplication gave origin to two tandem paralogues, Pgbc and Pgc2. Preliminary data from the genome sequence of the coelacanth (Latimeria chalumnae) suggests that the duplication postdates the divergence of this basal Sarcopterygii lineage. Pgc2 was maintained in most tetrapod species, but not in placental mammals. Episodes of lineage specific expansion were also observed in the opossum. As for the Pgbc gene, it expanded independently in the western clawed frog to held four gene copies (Fig. 5). Following the separation of amphibians but before amniote divergence, the Pgbc gene tandem duplicated to originate Pgc1 and Pgb (Fig. 4), the latter being translocated from the Pgc locus in mammals. Pgc1 was retained in most species, but not in the chicken and turkey, while Pgb experienced events of loss in some mammalian species, namely humans (Fig. 5). One anolis sequence (Pgc1) is inconsistently placed with both phylogenetic methods. In the NJ tree, it groups with the opossum Pgc1 and basal to all other mammalian Pgc1 genes. However, in the ML tree the same sequence is basal to the Pgb clade. If we consider the ML tree pattern correct, then this new gene represents a new lineage which emerged in the ancestor of amniotes but was lost subsequently in birds (1 event), and mammals (second event), plus the loss of Pgc1 in the reptile. In contrast, the NJ tree requires less duplication and loss events. Thus, we consider more parsimonious to conclude that the anolis sequence is a true Pgc1 gene. The position of the sequence in the Pgc gene cluster is also in agreement with this interpretation. Although this is only indicative evidence, this gene maps on the side of Tfeb, just as is observed in other species.


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)

Proposed evolutionary history and duplication timings of the Pgc gene family in vertebrates.Numbers inside each box denotes gene numbers.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0032852-g005: Proposed evolutionary history and duplication timings of the Pgc gene family in vertebrates.Numbers inside each box denotes gene numbers.
Mentions: Here we analyse the evolutionary history of a gene family involved in the vertebrate gastric function, the Pgc, to find that extensive gene duplication and loss occurred in vertebrate classes. Our research begun by inquiring a long held premise that Pgc is a single copy gene family in vertebrate species [3], [9], [10], [11]. By taking an exhaustive search into various vertebrate genomes, we demonstrate that significant discrepancy in Pgc complements exists between species. For example, we find no Pgc-like gene in some teleost species (e.g. medaka), while up to five genes are found in the opossum and the western clawed frog. We next undertook a combination of phylogenetics and chromosomal gene location (and their neighbouring gene families) to reconstruct gene duplication timings and processes, relative to the divergence of major vertebrate classes. Our analysis supports an evolutionary scenario where tandem gene duplication and gene loss have dynamically taken place in the tetrapod lineage (Fig. 5). Consequently, we introduce a new gene nomenclature that incorporates the phylogenetic findings. Before the diversification of tetrapods, a gene duplication gave origin to two tandem paralogues, Pgbc and Pgc2. Preliminary data from the genome sequence of the coelacanth (Latimeria chalumnae) suggests that the duplication postdates the divergence of this basal Sarcopterygii lineage. Pgc2 was maintained in most tetrapod species, but not in placental mammals. Episodes of lineage specific expansion were also observed in the opossum. As for the Pgbc gene, it expanded independently in the western clawed frog to held four gene copies (Fig. 5). Following the separation of amphibians but before amniote divergence, the Pgbc gene tandem duplicated to originate Pgc1 and Pgb (Fig. 4), the latter being translocated from the Pgc locus in mammals. Pgc1 was retained in most species, but not in the chicken and turkey, while Pgb experienced events of loss in some mammalian species, namely humans (Fig. 5). One anolis sequence (Pgc1) is inconsistently placed with both phylogenetic methods. In the NJ tree, it groups with the opossum Pgc1 and basal to all other mammalian Pgc1 genes. However, in the ML tree the same sequence is basal to the Pgb clade. If we consider the ML tree pattern correct, then this new gene represents a new lineage which emerged in the ancestor of amniotes but was lost subsequently in birds (1 event), and mammals (second event), plus the loss of Pgc1 in the reptile. In contrast, the NJ tree requires less duplication and loss events. Thus, we consider more parsimonious to conclude that the anolis sequence is a true Pgc1 gene. The position of the sequence in the Pgc gene cluster is also in agreement with this interpretation. Although this is only indicative evidence, this gene maps on the side of Tfeb, just as is observed in other species.

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