Ghost Loci Imply Hox and ParaHox Existence in the Last Common Ancestor of Animals

SummaryHox genes are renowned for patterning animal development, with widespread roles in developmental gene regulation. Despite this importance, their evolutionary origin remains obscure, due to absence of Hox genes (and their evolutionary sisters, the ParaHox genes) from basal lineages and because the phylogenies of these genes are poorly resolved [1–7]. This has led to debate about whether Hox and ParaHox genes originated coincidently with the origin of animals or instead evolved after the divergence of the earliest animal lineages [7, 8]. Here we use genomic synteny and Monte Carlo-based simulations to resolve Hox/ParaHox origins, our approach being independent of poorly resolved homeodomain phylogenies and better able to accommodate gene loss. We show Trox-2 of placozoans occupies a ParaHox locus. In addition, a separate locus sharing synteny and hence homology with human Hox loci exists in the placozoan genome, but without a Hox-like gene in it. We call this second locus a “ghost” Hox locus, because it is homologous to the human Hox loci, but does not itself contain a Hox gene. Extending our approach to sponges, we discover distinct ghost Hox and ParaHox loci. Thus, distinct Hox and ParaHox loci were present in the last common ancestor of all living animal lineages

Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus

Bats are exceptional among mammals for harbouring diverse pathogens and for their robust immune systems. In addition, bats are unusually long-lived and show low rates of cancer. Contiguous and complete reference genomes are needed to determine the genetic basis of these adaptations and establish bats as models for research into mammalian health. Here we sequenced and analysed the genomes of the Jamaican fruit bat ( Artibeus jamaicensis ) and the Mesoamerican mustached bat ( Pteronotus mesoamericanus ). We sequenced these two species using a mix of Illumina and Oxford Nanopore Technologies (ONT), assembling draft genomes with some of the highest contig N50s (28-29Mb) of bat genomes to date. Work is in progress to increase the base-level accuracies of these genomes. We conducted gene annotation and identified a set of 10,928 orthologs from bats and mammalian outgroups including humans, rodents, horses, pigs, and dogs. To detect positively selected genes as well as lineage-specific gene gains and losses, we carried out comprehensive branch-site likelihood ratio tests and gene family size analyses. Our analysis found signatures of rapid evolution in the innate immune response genes of bats, and evidence of past infections with diverse viral clades in Artibeus jamaicensis and Pteronotus mesoamericanus . We additionally found evidence of positive selection of tumor suppressors, which may play a role in the low cancer rates, in the most recent common ancestor of bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health

Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano.

The free-living flatworm, Macrostomum lignano has an impressive regenerative capacity. Following injury, it can regenerate almost an entirely new organism because of the presence of an abundant somatic stem cell population, the neoblasts. This set of unique properties makes many flatworms attractive organisms for studying the evolution of pathways involved in tissue self-renewal, cell-fate specification, and regeneration. The use of these organisms as models, however, is hampered by the lack of a well-assembled and annotated genome sequences, fundamental to modern genetic and molecular studies. Here we report the genomic sequence of M. lignano and an accompanying characterization of its transcriptome. The genome structure of M. lignano is remarkably complex, with ∼75% of its sequence being comprised of simple repeats and transposon sequences. This has made high-quality assembly from Illumina reads alone impossible (N50=222 bp). We therefore generated 130× coverage by long sequencing reads from the Pacific Biosciences platform to create a substantially improved assembly with an N50 of 64 Kbp. We complemented the reference genome with an assembled and annotated transcriptome, and used both of these datasets in combination to probe gene-expression patterns during regeneration, examining pathways important to stem cell function.This work is supported by National Institutes of Health Grants R37 GM062534 (to G.J.H.) and R01-HG006677 (to M.S.); National Science Foundation Grant DBI-1350041 (to M.S.); and a Swiss National Science Foundation Grant 31003A-143732 (to L.S.). This work was performed with assistance from Cold Spring Harbor Laboratory Shared Resources, which are funded, in part, by Cancer Center Support Grant 5P30CA045508.This is the final version of the article. It first appeared from PNAS via http://dx.doi.org/10.1073/pnas.151671811

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200

The origin of the Hox and ParaHox loci and animal homeobox evolution

The homeobox superfamily is one of the most significant gene families in the evolution of developmental processes in animals. Within this superfamily the ANTP class has expanded exclusively in animals and, therefore, the reconstruction of its origin and diversification into the different ‘modern’ families have become prominent questions in the ‘evo-devo’ field. The current burgeoning availability of animal genome sequences is improving the resolution of these questions, putting them in a genome evolution context, as well as providing the field with a large, detailed and diverse catalogue of animal homeobox complements. Here I have contributed with a new hypothesis on the origin and evolution of the Hox and ParaHox loci and the new term, ghost loci, referring to homologous genome regions that have lost their homeobox genes. This hypothesis proposes that the last common ancestor of all animals had a much more complex genome (i.e. differentiated Hox, ParaHox and NK loci) that underwent a simplification in the early animal lineages of sponges and placozoans. In collaboration with the Adamska group I resolved the orthology of the first ever ParaHox genes reported in calcareous sponges. This finding serves as an independent confirmation of the ghost loci hypothesis and further resolves the events of secondary simplification within the sponge lineage. Finally, I have catalogued the homeobox complement of the newly sequenced arthropod, the myriapod Strigamia maritima, and examined the linkage and clustering of these genes. This has furthered our understanding of the evolution of the ANTP class. The diversity of the homeobox complement and the retention in this myriapod and the retention of some homeobox genes not previously described within arthropods, in combination with the interesting phylogenetic position that this lineage occupies relative to other arthropods, makes this complement an important point of reference for comparison within the arthropods and in a broader perspective in the ecdyzosoans. These findings have provided significant further insights into the origin and evolution of the homeobox superfamily, with important implications for animal evolution and the evolution of development

Mechanisms of gene duplication and translocation and progress towards understanding their relative contributions to animal genome evolution

Duplication of genetic material is clearly a major route to genetic change, with consequences for both evolution and disease. A variety of forms and mechanisms of duplication are recognised, operating across the scales of a few base pairs upto entire genomes. With the ever-increasing amounts of gene and genome sequence data that are becoming available, our understanding of the extent of duplication is greatly improving, both in terms of the scales of duplication events as well as their rates of occurrence. An accurate understanding of these processes is vital if we are to properly understand important events in evolution as well as mechanisms operating at the level of genome organisation. Here we will focus on duplication in animal genomes and how the duplicated sequences are distributed, with the aim of maintaining a focus on principles of evolution and organisation that are most directly applicable to the shaping of our own genome.Publisher PDFPeer reviewe

A Caenorhabditis elegans Model for Integrating the Functions of Neuropsychiatric Risk Genes Identifies Components Required for Normal Dendritic Morphology

Analysis of patient-derived DNA samples has identified hundreds of variants that are likely involved in neuropsychiatric diseases such as autism spectrum disorder (ASD) and schizophrenia (SCZ). While these studies couple behavioral phenotypes to individual genotypes, the number and diversity of candidate genes implicated in these disorders highlights the fact that the mechanistic underpinnings of these disorders are largely unknown. Here, we describe a RNAi-based screening platform that uses C. elegans to screen candidate neuropsychiatric risk genes (NRGs) for roles in controlling dendritic arborization. To benchmark this approach, we queried published lists of NRGs whose variants in ASD and SCZ are predicted to result in complete or partial loss of gene function. We found that a significant fraction (>16%) of these candidate NRGs are essential for dendritic development. Furthermore, these gene sets are enriched for dendritic arbor phenotypes (>14 fold) when compared to control RNAi datasets of over 500 human orthologs. The diversity of PVD structural abnormalities observed in these assays suggests that the functions of diverse NRGs (encoding transcription factors, chromatin remodelers, molecular chaperones and cytoskeleton-related proteins) converge to regulate neuronal morphology and that individual NRGs may play distinct roles in dendritic branching. We also demonstrate that the experimental value of this platform by providing additional insights into the molecular frameworks of candidate NRGs. Specifically, we show that ANK2/UNC-44 function is directly integrated with known regulators of dendritic arborization and suggest that altering the dosage of ARID1B/LET-526 expression during development affects neuronal morphology without diminishing aspects of cell fate specification