SummaryThe interrelationships of the flatworms (phylum Platyhelminthes) are poorly resolved despite decades of morphological and molecular phylogenetic studies [1, 2]. The earliest-branching clades (Catenulida, Macrostomorpha, and Polycladida) share spiral cleavage and entolecithal eggs with other lophotrochozoans. Lecithoepitheliata have primitive spiral cleavage but derived ectolecithal eggs. Other orders (Rhabdocoela, Proseriata, Tricladida and relatives, and Bothrioplanida) all have derived ectolecithal eggs but have uncertain affinities to one another. The orders of parasitic Neodermata emerge from an uncertain position from within these ectolecithal classes. To tackle these problems, we have sequenced transcriptomes from 18 flatworms and 5 other metazoan groups. The addition of published data produces an alignment of >107,000 amino acids with less than 28% missing data from 27 flatworm taxa in 11 orders covering all major clades. Our phylogenetic analyses show that Platyhelminthes consist of the two clades Catenulida and Rhabditophora. Within Rhabditophora, we show the earliest-emerging branch is Macrostomorpha, not Polycladida. We show Lecithoepitheliata are not members of Neoophora but are sister group of Polycladida, implying independent origins of the ectolecithal eggs found in Lecithoepitheliata and Neoophora. We resolve Rhabdocoela as the most basally branching euneoophoran taxon. Tricladida, Bothrioplanida, and Neodermata constitute a group that appears to have lost both spiral cleavage and centrosomes. We identify Bothrioplanida as the long-sought closest free-living sister group of the parasitic Neodermata. Among parasitic orders, we show that Cestoda are closer to Trematoda than to Monogenea, rejecting the concept of the Cercomeromorpha. Our results have important implications for understanding the evolution of this major phylum.

A long-standing belief is that aging (senescence) is the result of stochastic damage accumulation. Alternatively, senescent pathology may also result from late-life, wild-type gene action (i.e., antagonistic pleiotropy, as argued by Williams) leading to non-adaptive run-on of developmental programs (or quasi-programs) (as suggested more recently by Blagosklonny). In this study, we use existing and new data to show how uterine tumors, a prominent form of senescent pathology in the nematode Caenorhabditis elegans, likely result from quasi-programs. Such tumors develop from unfertilized oocytes which enter the uterus and become hypertrophic and replete with endoreduplicated chromatin masses. Tumor formation begins with ovulation of unfertilized oocytes immediately after exhaustion of sperm stocks. We show that the timing of this transition between program and quasi-program (i.e., the onset of senescence), and the onset of tumor formation, depends upon the timing of sperm depletion. We identify homology between uterine tumors and mammalian ovarian teratomas, which both develop from oocytes that fail to mature after meiosis I. In teratomas, futile activation of developmental programs leads to the formation of differentiated structures within the tumor. We report that older uterine tumors express markers of later embryogenesis, consistent with teratoma-like activation of developmental programs. We also present evidence of coupling of distal gonad atrophy to oocyte hypertrophy. This study shows how the Williams Blagosklonny model can provide a mechanistic explanation of this component of C. elegans aging. It also suggests etiological similarity between teratoma and some forms of senescent pathology, insofar as both are caused by quasi-programs.

Animals detect light using opsin photopigments. Xenopsin, a recently classified subtype of opsin, challenges our views on opsin and photoreceptor evolution. Originally thought to belong to the Gαi-coupled ciliary opsins, xenopsins are now understood to have diverged from ciliary opsins in pre-bilaterian times, but little is known about the cells that deploy these proteins, or if they form a photopigment and drive phototransduction. We characterized xenopsin in a flatworm, Maritigrella crozieri, and found it expressed in ciliary cells of eyes in the larva, and in extraocular cells around the brain in the adult. These extraocular cells house hundreds of cilia in an intra-cellular vacuole (phaosome). Functional assays in human cells show Maritigrella xenopsin drives phototransduction primarily by coupling to Gαi. These findings highlight similarities between xenopsin and c-opsin and reveal a novel type of opsin-expressing cell that, like jawed vertebrate rods, encloses the ciliary membrane within their own plasma membrane.