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Telford, M.

Publications and source records attributed to Telford, M..

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OMA standalone: orthology inference among public and custom genomes and transcriptomes

Genomes and transcriptomes are now typically sequenced by individual labs, but analysing them often remains challenging. One essential step in many analyses lies in identifying orthologs--corresponding genes across multiple species--but this is far from trivial. The OMA (Orthologous MAtrix) database is a leading resource for identifying orthologs among publicly available, complete genomes. Here, we describe the OMA pipeline available as a standalone program for Linux and Mac. When run on a cluster, it has native support for the LSF, SGE, PBS Pro, and Slurm job schedulers and can scale up to thousands of parallel processes. Another key feature of OMA standalone is that users can combine their own data with existing public data by exporting genomes and pre-computed alignments from the OMA database, which currently contains over 2100 complete genomes. We compare OMA standalone to other methods in the context of phylogenetic tree inference, by inferring a phylogeny of the Lophotrochozoa, a challenging clade within the Protostomes. We also discuss other potential applications of OMA standalone, including identifying gene families having undergone duplications/losses in specific clades, and identifying potential drug targets in non-model organisms. OMA Standalone is available at http://omabrowser.org/standalone under the permissible open source Mozilla Public License Version 2.0.

bioinformatics

The mitochondrial genomes of the mesozoans Intoshia linei, Dicyema sp., and Dicyema japonicum

The Dicyemida and Orthonectida are two groups of tiny, simple, vermiform parasites that have historically been united in a group named the Mesozoa. Both Dicyemida and Orthonectida have just two cell layers and appear to lack any defined tissues. They were initially thought to be evolutionary intermediates between protozoans and metazoans but more recent analyses indicate that they are protostomian metazoans that have undergone secondary simplification from a complex ancestor. Here we describe the first almost complete mitochondrial genome sequence from an orthonectid, Intoshia linei, and describe nine and eight mitochondrial protein-coding genes from Dicyema sp. and Dicyema japonicum, respectively. The 14,247 base pair long I. linei sequence has typical metazoan gene content, but is exceptionally AT-rich, and has a divergent gene order compared to other metazoans. The data we present from the Dicyemida provide very limited support for the suggestion that dicyemid mitochondrial genes are found on discrete mini-circles, as opposed to the large circular mitochondrial genomes that are typical across the Metazoa. The cox1 gene from dicyemid species has a series of conserved in-frame deletions that is unique to this lineage. Using cox1 genes from across the genus Dicyema, we report the first internal phylogeny of this group.\n\nKey FindingsO_LIWe report the first almost-complete mitochondrial genome from an orthonectid parasite, Intoshia linei, including 12 protein-coding genes; 20 tRNAs and putative sequences for large and small subunit rRNAs. We find that the I. linei mitochondrial genome is exceptionally AT-rich and has a novel gene order compared to other published metazoan mitochondrial genomes. These findings are indicative of the rapid rate of evolution that has occurred in the I. linei mitochondrial genome.\nC_LIO_LIWe also report nine and eight protein-coding genes, respectively, from the dicyemid species Dicyema sp. and Dicyema japonicum, and use the cox1 genes from both species for phylogenetic inference of the internal phylogeny of the dicyemids.\nC_LIO_LIWe find that the cox1 gene from dicyemids has a series of four conserved in-frame deletions which appear to be unique to this group.\nC_LI

evolutionary biology

Monsters in the uterus: A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans

Many diseases whose frequency increases with advancing age are caused by aging (senescence), but the mechanisms of senescence remain poorly understood. According to G.C. Williams and M.V. Blagosklonny, a major etiological determinant of senescence is late-life, wild-type gene action and non-adaptive execution of biological programs (or quasi-programs). These generate a wide range of senescent pathologies causing illness and death. Here we investigate the etiology of a prominent senescent pathology in the nematode C. elegans, uterine tumors, in the light of the Williams Blagosklonny theory. Uterine tumors develop from unfertilized, immature oocytes which execute incomplete embryogenetic programs. This includes extensive endomitosis, leading to formation of chromatin masses and cellular hypertrophy. The starting point of pathogenesis is exhaustion of sperm stocks. The timing of this transition between program and quasi-program can be altered by blocking sperm production (causing earlier tumors) or supplying additional sperm by mating (delaying tumor onset). Other pathophysiological determinants are yolk consumption by tumors, and bacterial proliferation within tumors. Uterine tumors resemble mammalian ovarian teratomas (tera, Greek: monster) in that both develop from oocytes that fail to mature after meiosis I, and both are the result of quasi-programs. Moreover, older but not younger uterine tumors show expression of markers of later embryogenesis, i.e. are teratoma-like. These results show how uterine tumors in C. elegans form as the result of run-on of embryogenetic quasi-programs. They also suggest fundamental etiological equivalence between teratoma and some forms of senescent pathology, insofar as both are caused by quasi-programs.

developmental biology

The mitochondrial genomes of the acoelomorph wormsParatomella rubra and Isodiametra pulchra

Acoels are small, ubiquitous, but understudied, marine worms with a very simple body plan. Their internal phylogeny is still in parts unresolved, and the position of their proposed phylum Xenacoelomorpha (Xenoturbella+Acoela) is still debated.\n\nHere we describe mitochondrial genome sequences from two acoel species: Paratomella rubra and Isodiametra pulchra. The 14,954 nucleotide-long P. rubra sequence is typical for metazoans in size and gene content. The larger I. pulchra mitochondrial genome contains both ribosomal genes, 21 tRNAs, but only 11 protein-coding genes. We find evidence suggesting a duplicated sequence in the I. pulchra mitochondrial genome.\n\nMitochondrial sequences for both P. rubra and I. pulchra have a unique genome organisation in comparison to other published metazoan mitochondrial genomes. We found a large degree of protein-coding gene and tRNA overlap in P. rubra, with little non-coding sequence making the genome compact. Conversely, the I. pulchra mitochondrial genome has many long non-coding sequences between genes, likely driving the genome size expansion. Phylogenetic trees inferred from concatenated alignments of mitochondrial genes grouped the fast-evolving Acoela and Tunicata, almost certainly due to the systematic error of long branch attraction: a reconstruction artefact that is probably compounded by the fast substitution rate of mitochondrial genes in this taxon.

evolutionary biology