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Surprising complexity of the ancestral apoptosis network.

ABSTRACT: Apoptosis, one of the main types of programmed cell death, is regulated and performed by a complex protein network. Studies in model organisms, mostly in the nematode Caenorhabditis elegans, identified a relatively simple apoptotic network consisting of only a few proteins. However, analysis of several recently sequenced invertebrate genomes, ranging from the cnidarian sea anemone Nematostella vectensis, representing one of the morphologically simplest metazoans, to the deuterostomes sea urchin and amphioxus, contradicts the current paradigm of a simple ancestral network that expanded in vertebrates.Here we show that the apoptosome-forming CED-4/Apaf-1 protein, present in single copy in vertebrate, nematode, and insect genomes, had multiple paralogs in the cnidarian-bilaterian ancestor. Different members of this ancestral Apaf-1 family led to the extant proteins in nematodes/insects and in deuterostomes, explaining significant functional differences between proteins that until now were believed to be orthologous. Similarly, the evolution of the Bcl-2 and caspase protein families appears surprisingly complex and apparently included significant gene loss in nematodes and insects and expansions in deuterostomes.The emerging picture of the evolution of the apoptosis network is one of a succession of lineage-specific expansions and losses, which combined with the limited number of 'apoptotic' protein families, resulted in apparent similarities between networks in different organisms that mask an underlying complex evolutionary history. Similar results are beginning to surface for other regulatory networks, contradicting the intuitive notion that regulatory networks evolved in a linear way, from simple to complex.

SUBMITTER: Zmasek CM

PROVIDER: S-EPMC2246300 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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Surprising complexity of the ancestral apoptosis network.

Zmasek Christian M CM Zhang Qing Q Ye Yuzhen Y Godzik Adam A

Genome biology 20070101 10

<h4>Background</h4>Apoptosis, one of the main types of programmed cell death, is regulated and performed by a complex protein network. Studies in model organisms, mostly in the nematode Caenorhabditis elegans, identified a relatively simple apoptotic network consisting of only a few proteins. However, analysis of several recently sequenced invertebrate genomes, ranging from the cnidarian sea anemone Nematostella vectensis, representing one of the morphologically simplest metazoans, to the deuter ...[more]

PMID: 17958905

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Project description:BACKGROUND:All surgical meshes entering the U.S. market have been cleared for clinical use by the 510(k) process of the Food and Drug Administration (FDA), in which devices simply require proof of "substantial equivalence" to predicate devices, without the need for clinical trials. However, recalled meshes associated with adverse effects may, indirectly, continue to serve as predicates for new devices raising concerns over the safety of the 510(k) route. METHODOLOGY:Here we assess the potential magnitude of this problem by determining the ancestral network of equivalence claims linking recently cleared surgical meshes. Using the FDA website we identified all surgical meshes cleared by the 510(k) route between January 2013 and December 2015 along with all listed predicates for these devices. Using a network approach, we trace the ancestry of predicates across multiple generations of equivalence claims and identify those meshes connected to devices that have since recalled from the market along with the reason for their recall. CONCLUSIONS:We find that the 77 surgical meshes cleared between 2013 and 2015 are based on 771 interconnected predicate claims of equivalence from 400 other devices. The vast majority of these devices (97%) are descended from only six surgical meshes that were present on the market prior to 1976. One of these ancestral meshes alone, provided the basis of 183 subsequent devices. Furthermore, we show that 16% of recently cleared devices are connected through equivalence claims to the 3 predicate meshes that have been recalled for design and material related flaws causing serious adverse events. Taken together, our results show that surgical meshes are connected through a tangled web of equivalency claims and many meshes recently cleared by the FDA have connections through chains of equivalency to devices which have been recalled from the market due to concerns over clinical safety. These findings raise concerns over the efficacy of the 510(k) route in ensuring patient safety.

Dataset Information

Surprising complexity of the ancestral apoptosis network.

Publications

Surprising complexity of the ancestral apoptosis network.

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