Clouse RM et al. (2015), Phylotranscriptomic analysis uncovers a wealth ...

ECB-ART-48270

R Soc Open Sci 2015 Dec 04;212:150377. doi: 10.1098/rsos.150377.

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Phylotranscriptomic analysis uncovers a wealth of tissue inhibitor of metalloproteinases variants in echinoderms.

Clouse RM , Linchangco GV , Kerr AM , Reid RW , Janies DA .

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Tissue inhibitors of metalloproteinases (TIMPs) help regulate the extracellular matrix (ECM) in animals, mostly by inhibiting matrix metalloproteinases (MMPs). They are important activators of mutable collagenous tissue (MCT), which have been extensively studied in echinoderms, and the four TIMP copies in humans have been studied for their role in cancer. To understand the evolution of TIMPs, we combined 405 TIMPs from an echinoderm transcriptome dataset built from 41 specimens representing all five classes of echinoderms with variants from protostomes and chordates. We used multiple sequence alignment with various stringencies of alignment quality to cull highly divergent sequences and then conducted phylogenetic analyses using both nucleotide and amino acid sequences. Phylogenetic hypotheses consistently recovered TIMPs as diversifying in the ancestral deuterostome and these early lineages continuing to diversify in echinoderms. The four vertebrate TIMPs diversified from a single copy in the ancestral chordate, all other copies being lost. Consistent with greater MCT needs owing to body wall liquefaction, evisceration, autotomy and reproduction by fission, holothuroids had significantly more TIMPs and higher read depths per contig. Ten cysteine residues, an HPQ binding site and several other residues were conserved in at least 70% of all TIMPs. The conservation of binding sites and the placement of echinoderm TIMPs involved in MCT modification suggest that ECM regulation remains the primary function of TIMP genes, although within this role there are a large number of specialized copies.

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Genes referenced: LOC115919351 LOC115925415 LOC583082

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	Figure 1. Stichopus horrens Selenka, 1867 before (a) and after (b) dermal liquefaction (photos: Katherine Brunson).
	Figure 2. Boxplots for the 405 TIMP genes identified in our transcriptome database, represented as a proportion of all contigs assembled from each taxon, and averaged across each of the five classes (a), as well as the average read depth per TIMP contig, as a proportion of all reads for each taxon, averaged for each class (b).
	Figure 3. Best tree recovered under maximum-likelihood using the final, selected terminal set of 180 echinoderm and 46 non-echinoderm sequences. They were aligned as amino acids then back-translated; the tree to the left was recovered from using coding sequences, and the tree to the right shows the result of tree-searching the same alignments translated to amino acids. Numbers Iâ€“IV denote key events in the evolution of deuterostome TIMPs, shown in figure 5.
	Figure 4. Simplified lineages-through-time (LTT) plots for TIMP genes in specimens with more than 10 copies in an alignment of 392 echinoderm TIMP coding sequences. The x-axis of each plot is the time since the root, and the y-axis is the number of lineages; the final lineage count is shown to the right of the final height. p-Values for the gamma statistic are shown for each specimen, lower values indicating a greater deviation from a constant rate of diversification.
	Figure 5. Schematic of key events in the evolution of TIMP genes in deuterostomes. After the split between Protostomia and Deuterostomia, there was a diversification of TIMPs which persisted into the five echinoderm classes (I). One early TIMP lineage was inherited by the ancestor of all chordates and is the progenitor of TIMPs 1â€“4 studied in vertebrates (II), and its sister lineage diversified and continued into the echinoderms (III). Of this latter lineage, one copy diversified much later in holothuroids, giving rise to the tensilin gene (IV).

References [+] :

Aberer, Pruning rogue taxa improves phylogenetic accuracy: an efficient algorithm and webservice. 2013, Pubmed