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Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization.

ABSTRACT: The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs) common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10), thrombotic thrombocytopenic purpura (ADAMTS13), and Ehlers-Danlos syndrome type VIIC (ADAMTS2) in humans and belted white-spotting mutation in mice (ADAMTS20).Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu), chordate (Ciona) and invertebrate (Drosophila and Caenorhabditis) ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans.The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15) that may have distinct aggrecanase and angiogenesis functions.

SUBMITTER: Nicholson AC

PROVIDER: S-EPMC549037 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization.

Nicholson Ainsley C AC Malik Shehre-Banoo SB Logsdon John M JM Van Meir Erwin G EG

BMC evolutionary biology 20050204

<h4>Background</h4>The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs) common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndro ...[more]

PMID: 15693998

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Project description:BackgroundThe protozoan pathogens Leishmania major, Trypanosoma brucei and Trypanosoma cruzi (the Tritryps) are parasites that produce devastating human diseases. These organisms show very unusual mechanisms of gene expression, such as polycistronic transcription. We are interested in the study of tRNA genes, which are transcribed by RNA polymerase III (Pol III). To analyze the sequences and genomic organization of tRNA genes and other Pol III-transcribed genes, we have performed an in silico analysis of the Tritryps genome sequences.ResultsOur analysis indicated the presence of 83, 66 and 120 genes in L. major, T. brucei and T. cruzi, respectively. These numbers include several previously unannotated selenocysteine (Sec) tRNA genes. Most tRNA genes are organized into clusters of 2 to 10 genes that may contain other Pol III-transcribed genes. The distribution of genes in the L. major genome does not seem to be totally random, like in most organisms. While the majority of the tRNA clusters do not show synteny (conservation of gene order) between the Tritryps, a cluster of 13 Pol III genes that is highly syntenic was identified. We have determined consensus sequences for the putative promoter regions (Boxes A and B) of the Tritryps tRNA genes, and specific changes were found in tRNA-Sec genes. Analysis of transcription termination signals of the tRNAs (clusters of Ts) showed differences between T. cruzi and the other two species. We have also identified several tRNA isodecoder genes (having the same anticodon, but different sequences elsewhere in the tRNA body) in the Tritryps.ConclusionA low number of tRNA genes is present in Tritryps. The overall weak synteny that they show indicates a reduced importance of genome location of Pol III genes compared to protein-coding genes. The fact that some of the differences between isodecoder genes occur in the internal promoter elements suggests that differential control of the expression of some isoacceptor tRNA genes in Tritryps is possible. The special characteristics found in Boxes A and B from tRNA-Sec genes from Tritryps indicate that the mechanisms that regulate their transcription might be different from those of other tRNA genes.

Project description:IntroductionThe recently established Linderniaceae, separated from the traditionally defined Scrophulariaceae, is a taxonomically complicated family. Although previous phylogenetic studies based on a few short DNA markers have made great contributions to the taxonomy of Linderniaceae, limited sampling and low resolution of the phylogenetic tree have failed to resolve controversies between some generic circumscriptions. The plastid genome exhibits a powerful ability to solve phylogenetic relationships ranging from shallow to deep taxonomic levels. To date, no plastid phylogenomic studies have been carried out in Linderniaceae.MethodsIn this study, we newly sequenced 26 plastid genomes of Linderniaceae, including eight genera and 25 species, to explore the phylogenetic relationships and genome evolution of the family through plastid phylogenomic and comparative genomic analyses.ResultsThe plastid genome size of Linderniaceae ranged from 152,386 bp to 154,402 bp, exhibiting a typical quartile structure. All plastomes encoded 114 unique genes, comprising 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. The inverted repeat regions were more conserved compared with the single-copy regions. A total of 1803 microsatellites and 1909 long sequence repeats were identified, and five hypervariable regions (petN-psbM, rps16-trnQ, rpl32-trnL, rpl32, and ycf1) were screened out. Most protein-coding genes were relatively conserved, with only the ycf2 gene found under positive selection in a few species. Phylogenomic analyses confirmed that Linderniaceae was a distinctive lineage and revealed that the presently circumscribed Vandellia and Torenia were non-monophyletic.DiscussionComparative analyses showed the Linderniaceae plastomes were highly conservative in terms of structure, gene order, and gene content. Combining morphological and molecular evidence, we supported the newly established Yamazakia separating from Vandellia and the monotypic Picria as a separate genus. These findings provide further evidence to recognize the phylogenetic relationships among Linderniaceae and new insights into the evolution of the plastid genomes.

Project description:BACKGROUND: Proteins of the mammalian PYHIN (IFI200/HIN-200) family are involved in defence against infection through recognition of foreign DNA. The family member absent in melanoma 2 (AIM2) binds cytosolic DNA via its HIN domain and initiates inflammasome formation via its pyrin domain. AIM2 lies within a cluster of related genes, many of which are uncharacterised in mouse. To better understand the evolution, orthology and function of these genes, we have documented the range of PYHIN genes present in representative mammalian species, and undertaken phylogenetic and expression analyses. RESULTS: No PYHIN genes are evident in non-mammals or monotremes, with a single member found in each of three marsupial genomes. Placental mammals show variable family expansions, from one gene in cow to four in human and 14 in mouse. A single HIN domain appears to have evolved in the common ancestor of marsupials and placental mammals, and duplicated to give rise to three distinct forms (HIN-A, -B and -C) in the placental mammal ancestor. Phylogenetic analyses showed that AIM2 HIN-C and pyrin domains clearly diverge from the rest of the family, and it is the only PYHIN protein with orthology across many species. Interestingly, although AIM2 is important in defence against some bacteria and viruses in mice, AIM2 is a pseudogene in cow, sheep, llama, dolphin, dog and elephant. The other 13 mouse genes have arisen by duplication and rearrangement within the lineage, which has allowed some diversification in expression patterns. CONCLUSIONS: The role of AIM2 in forming the inflammasome is relatively well understood, but molecular interactions of other PYHIN proteins involved in defence against foreign DNA remain to be defined. The non-AIM2 PYHIN protein sequences are very distinct from AIM2, suggesting they vary in effector mechanism in response to foreign DNA, and may bind different DNA structures. The PYHIN family has highly varied gene composition between mammalian species due to lineage-specific duplication and loss, which probably indicates different adaptations for fighting infectious disease. Non-genomic DNA can indicate infection, or a mutagenic threat. We hypothesise that defence of the genome against endogenous retroelements has been an additional evolutionary driver for PYHIN proteins.

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Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization.

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Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization.

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