Hox genes are not always Colinear

The deuterostomes are the clade of animals for which we have the most detailed understanding of Hox cluster organisation. With the Hox cluster of amphioxus (Branchiostoma floridae) we have the best prototypical, least derived Hox cluster for the group, whilst the urochordates present us with some of the most highly derived and disintegrated clusters. Combined with the detailed mechanistic understanding of vertebrate Hox regulation, the deuterostomes provide much of the most useful data for understanding Hox cluster evolution. Considering both the prototypical and derived deuterostome Hox clusters leads us to hypothesize that Temporal Colinearity is the main constraining force on Hox cluster organisation, but until we have a much deeper understanding of the mechanistic basis for this phenomenon, and know how widespread across the Bilateria the mechanism(s) is/are, then we cannot know how the Hox cluster of the last common bilaterian operated and what have been the major evolutionary forces operating upon the Hox gene cluster

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

Evolutionary diversification of the canonical Wnt signaling effector TCF/LEF in chordates

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), linked projects, references BB/S016856/1 and BB/S020640/1.Wnt signaling is essential during animal development and regeneration, but also plays an important role in diseases such as cancer and diabetes. The canonical Wnt signaling pathway is one of the most conserved signaling cascades in the animal kingdom, with the T-cell factor/lymphoid enhancer factor (TCF/LEF) proteins the major mediators of Wnt/β-catenin-regulated gene expression. In comparison to invertebrates, vertebrates possess a high diversity of TCF/LEF family genes, implicating this as a possible key change to Wnt signaling at the evolutionary origin of vertebrates. However, the precise nature of this diversification is only poorly understood. The aim of this study is to clarify orthology, paralogy and isoform relationships within the TCF/LEF gene family within chordates via in silico comparative study of TCF/LEF gene structure, molecular phylogeny and gene synteny. Our results support the notion that the four TCF/LEF paralog subfamilies in jawed vertebrates (gnathostomes) evolved via the two rounds of whole-genome duplication that occurred during early vertebrate evolution. Importantly, gene structure comparisons and synteny analysis of jawless vertebrate (cyclostome) TCFs suggest that a TCF7L2-like form of gene structure is a close proxy for the ancestral vertebrate structure. In conclusion, we propose a detailed evolutionary path based on a new pre-whole-genome duplication vertebrate TCF gene model. This ancestor gene model highlights the chordate and vertebrate innovations of TCF/LEF gene structure, providing the foundation for understanding the role of Wnt/β-catenin signaling in vertebrate evolution.Publisher PDFPeer reviewe

Sampling the fish gill microbiome : a comparison of tissue biopsies and swabs

Funding Information: The research costs of this work were supported by the BBSRC EASTBIO DTP and Marine Alliance for Science and Technology Scotland (MASTS) small grants funding scheme. Acknowledgements The authors would like to thank Scottish Sea Farms (SSF) for the kind facilitation of fieldwork that provided material in this project, particularly the staff at the Loch Spelve facility, and the health team at SSF, particularly Dr. Ralph Bickerdike. Thanks are due as well to Professor Matt Holden and Kerry Pettigrew of the Infection Group within the Biomedical Sciences Research Complex, School of Medicine, University of St Andrews, for assistance within the laboratory, as well as Dr. David Bass at the Centre for Environment Fisheries and Aquaculture Science for helpful proofreading.Peer reviewedPublisher PD

The Amphioxus Hox Cluster: Characterization, Comparative Genomics, and Evolution

The amphioxus Hox cluster is often viewed as “archetypal” for the chordate lineage. Here we present a descriptive account of the 448kb region spanning the Hox cluster of the amphioxus Branchiostoma floridae from Hox14 to Hox1.We provide complete coding sequences of all 14 previously described amphioxus sequences and describe a detailed analysis of the conserved non-coding regulatory sequence elements. We find that the posterior part of the Hox cluster is so highly derived that even the complete genomic sequence is insufficient to decide whether the posterior Hox genes arose by independent duplications or whether they are true orthologs of the corresponding gnathostome paralog groups. In contrast, the anterior region is much better conserved. The amphioxus Hox cluster strongly excludes repetitive elements with the exception of two repeat islands in the posterior region. Repeat exclusion is also observed in gnathostomes, but not protostome Hox clusters. We thus hypothesize that the much shorter vertebrate Hox clusters are the result of extensive resolution of the redundancy of regulatory DNA following the genome duplications rather than the consequence of a selection pressure to remove non-functional sequence from the cluster

MicroRNA clusters integrate evolutionary constraints on expression and target affinities : the miR-6/5/4/286/3/309 cluster in Drosophila

This research was supported by the Hong Kong Research Grant Council GRF Grant (14103516), The Chinese University of Hong Kong Direct Grant (4053248), and TUYF Charitable Trust (6903957) (JHLH).A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs.PostprintPeer reviewe

Introduction to <i>Hox modules in evolution and development</i>

Hox genes revolutionised the field of evolutionary developmental biology (evo-devo), giving us unprecedented insight into how the animal kingdom evolved from a molecular perspective. The fields of developmental and evolutionary biology overlap significantly and are mutually beneficial, and this synergy manifests itself as evo-devo, demonstrating that neither field can be properly understood without the other. Hox genes are key to this endeavour. We are now embarking on a new revolution in Hox biology, stimulated by significant technical developments in genome sequencing and functional genetics. These new techniques are releasing us from the previous constraints of having to focus on genetically tractable ‘model species’ to obtain molecular mechanistic insights. Understanding the origins of the beautiful diversity of animal life is now within our reach, and this book provides a window on how we are starting out on this exciting journey.</p

Introduction to <i>Hox modules in evolution and development</i>

Hox genes revolutionised the field of evolutionary developmental biology (evo-devo), giving us unprecedented insight into how the animal kingdom evolved from a molecular perspective. The fields of developmental and evolutionary biology overlap significantly and are mutually beneficial, and this synergy manifests itself as evo-devo, demonstrating that neither field can be properly understood without the other. Hox genes are key to this endeavour. We are now embarking on a new revolution in Hox biology, stimulated by significant technical developments in genome sequencing and functional genetics. These new techniques are releasing us from the previous constraints of having to focus on genetically tractable ‘model species’ to obtain molecular mechanistic insights. Understanding the origins of the beautiful diversity of animal life is now within our reach, and this book provides a window on how we are starting out on this exciting journey.</p