Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci

Abstract

Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species.

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

“…Knockdown of ADAM19 phenocopies ADAM13 loss of function in X. tropicalis embryos Our phylogenetic and syntenic (gene linkage) analyses suggest that ADAM12, ADAM13 and ADAM19 form a subfamily of proteolytically active ADAMs that is conserved among vertebrates (note that the mammalian ortholog of Xenopus ADAM13 is ADAM33) (Bahudhanapati et al, 2015;Wei et al, 2010a). Similar to its X. laevis ortholog ), X. tropicalis adam19 was found to be expressed in the dorsal mesoderm during midgastrulation, and broadly in the dorsal ectoderm at the end of gastrulation ( Fig.…”

“…The striking similarity between the loss-of-function phenotypes of ADAM13 and ADAM19 implies a connection between the in vivo roles of these two metalloproteinases. Because ADAM19 is one of the closest paralogs of ADAM13 (Bahudhanapati et al, 2015;Wei et al, 2010a), the simplest explanation is that these two ADAMs have redundant functions. To examine whether this is the case, we first compared the in vivo roles of the protease activities of ADAM13 and ADAM19.…”

ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126

“…At present, most GC patients are clinically diagnosed in the advanced stages and the median survival time of GC patients with local invasion or metastasis is less than 12 months (2). The challenges of discovering associated tumor markers and understanding the mechanisms of GC initiation, progression and metastasis, are the keys to diagnose, prevent and treat GC appropriately in the early stages as well as develop targeted treatment 3A disintegrin and metalloproteinases (ADAMs), are a family of proteins which play a pivotal role in the proteolytic process implicated in cell-cell and cell-matrix interactions (4). Members of the ADAM family are divided into two groups: membrane-anchored and the secreted-type proteins (ADAMST) (5).…”

Canonical Wnt Mechanisms in Neural Crest Induction

“…Knockdown of ADAM19 phenocopies ADAM13 loss of function in X. tropicalis embryos Our phylogenetic and syntenic (gene linkage) analyses suggest that ADAMs 12, 13 and 19 form a subfamily of proteolytically active ADAMs that is conserved among vertebrates (note that the mammalian ortholog of Xenopus ADAM13 is ADAM33) (Bahudhanapati et al, 2015;Wei et al, 2010a). Similar to its X. laevis ortholog , X. tropicalis adam19 was found to be expressed in the dorsal mesoderm during mid-gastrulation, and broadly in the dorsal ectoderm at the end of gastrulation (Figs.…”

“…Because ADAM19 is one of the closest paralogs of ADAM13 (Bahudhanapati et al, 2015;Wei et al, 2010a), the simplest explanation is that these two ADAMs have redundant functions. To examine if this is the case, we first compared the in vivo roles of the protease activities of ADAMs 13 and 19.…”