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

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...

金属蛋白酶组织抑制剂（Tissue inhibitors of metalloproteinases, TIMPs）主要通过抑制基质金属蛋白酶（matrix metalloproteinases, MMPs），参与调控动物体内的细胞外基质（extracellular matrix, ECM）。它们是可变胶原组织（mutable collagenous tissue, MCT）的重要激活因子，该类因子已在棘皮动物（echinoderms）中得到广泛研究，而人类体内的4种TIMP拷贝在癌症发生中的作用也已被深入探究。为解析TIMP家族的演化历程，本研究整合了由覆盖棘皮动物全部5个纲的41份标本构建的棘皮动物转录组数据集中的405条TIMP序列，以及原口动物（protostomes）与脊索动物（chordates）中的TIMP变异序列。研究采用不同严格程度的比对质量标准开展多序列比对，以剔除高度趋异的序列，随后分别基于核苷酸序列与氨基酸序列进行系统发育分析。系统发育假说一致显示，TIMP家族在后口动物（deuterostome）祖先类群中发生分化，且这些早期谱系在棘皮动物中持续演化扩张。脊椎动物的4种TIMP均由单拷贝基因演化而来……