Improved understanding of the role of gene and genome duplications in chordate evolution with new genome and transcriptome sequences

Funding: MEA-R is supported by funding from the University of St Andrews School of Biology and St Leonard’s College. Work in the lab of DEKF is funded by the BBSRC (BB/S016856/1) with additional support from the European project Assemble Plus (H2020-INFRAIA-1-2016–2017; grant no. 730984).Comparative approaches to understanding chordate genomes have uncovered a significant role for gene duplications, including whole genome duplications, giving rise to and expanding gene families. In developmental biology, gene families created and expanded by both tandem and whole genome duplications (WGDs) are paramount. These genes, often involved in transcription and signalling, are candidates for underpinning major evolutionary transitions because they are particularly prone to retention and subfunctionalisation, neofunctionalisation, or specialisation following duplication. Under the subfunctionalisation model, duplication lays the foundation for the diversification of paralogues, especially in the context of gene regulation. Tandemly duplicated paralogues reside in the same regulatory environment, which may constrain them and result in a gene cluster with closely linked but subtly different expression patterns and functions. Ohnologues (WGD paralogues) often diversify by partitioning their expression domains between retained paralogues, amidst the many changes in the genome during rediploidisation, including chromosomal rearrangements and extensive gene losses. The patterns of these retentions and losses is still not fully understood, nor is the full extent of the impact of gene duplication on chordate evolution. The growing number of sequencing projects, genomic resources, transcriptomics, and improvements to genome assemblies for diverse chordates from non-model and under-sampled lineages like the coelacanth, as well as key lineages, such as amphioxus and lamprey, has allowed more informative comparisons within developmental gene families as well as revealing the extent of conserved synteny across whole genomes. This influx of data provides the tools necessary for phylogenetically-informed comparative genomics, which will bring us closer to understanding the evolution of chordate body plan diversity and the changes underpinning the origin and diversification of vertebrates.Publisher PDFPeer reviewe

More than one-to-four via 2R : evidence of an independent amphioxus expansion and two-gene ancestral vertebrate state for MyoD-related Muscle Regulatory Factors (MRFs)

Funding: Madeleine Aase-Remedios and Dr Clara Coll-Lladówere supported by funding from the University of St Andrews, School of Biology and additional support from the CORBEL grant European Research Infrastructure cluster project.The evolutionary transition from invertebrates to vertebrates involved extensive gene duplication, but understanding precisely how such duplications contributed to this transition requires more detailed knowledge of specific cases of genes and gene families. MyoD (Myogenic differentiation) has long been recognized as a master developmental control gene and member of the MyoD family of bHLH transcription factors (Myogenic regulatory factors, MRFs) that drive myogenesis across the bilaterians. Phylogenetic reconstructions within this gene family are complicated by multiple instances of gene duplication and loss in several lineages. Following two rounds of whole genome duplication (2R WGD) at the origin of the vertebrates the ancestral function of MRFs is thought to have become partitioned amongst the daughter genes, so that MyoD and Myf5 act early in myogenic determination while Myog and Myf6 are expressed later, in differentiating myoblasts. Comparing chordate MRFs, we find an independent expansion of MRFs in the invertebrate chordate amphioxus, with evidence for a parallel instance of subfunctionalisation relative to that of vertebrates. Conserved synteny between chordate MRF loci supports the 2R WGD events as a major force in shaping the evolution of vertebrate MRFs. We also resolve vertebrate MRF complements and organization, finding a new type of vertebrate MRF gene in the process, which allowed us to infer an ancestral two-gene state in the vertebrates corresponding to the early- and late-acting types of MRFs. This necessitates a revision of previous conclusions about the simple one-to-four origin of vertebrate MRFs.Publisher PDFPeer reviewe

Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle

Madeleine E. Aase-Remedios and Clara Coll-Lladó were supported by funding from the University of St Andrews, School of Biology and additional support from St Leonards College (MEAR), the CORBEL grant European Research Infrastructure cluster project and European Assemble Plus (H2020-INFRAIA-1-2016-2017; grant no.730984). Transcriptome sequencing was done with an award under the BBSRC TGAC Capacity and Capability Challenge.Background:   The formation and functioning of muscles are fundamental aspects of animal biology, and the evolution of ‘muscle genes’ is central to our understanding of this tissue. Feeding-fasting-refeeding experiments have been widely used to assess muscle cellular and metabolic responses to nutrition. Though these studies have focused on vertebrate models and only a few invertebrate systems, they have found similar processes are involved in muscle degradation and maintenance. Motivation for these studies stems from interest in diseases whose pathologies involve muscle atrophy, a symptom also triggered by fasting, as well as commercial interest in the muscle mass of animals kept for consumption. Experimentally modelling atrophy by manipulating nutritional state causes muscle mass to be depleted during starvation and replenished with refeeding so that the genetic mechanisms controlling muscle growth and degradation can be understood. Results:  Using amphioxus, the earliest branching chordate lineage, we address the gap in previous work stemming from comparisons between distantly related vertebrate and invertebrate models. Our amphioxus feeding-fasting-refeeding muscle transcriptomes reveal a highly conserved myogenic program and that the pro-orthologues of many vertebrate myoblast fusion genes were present in the ancestral chordate, despite these invertebrate chordates having unfused mononucleate myocytes. We found that genes differentially expressed between fed and fasted amphioxus were orthologous to the genes that respond to nutritional state in vertebrates. This response is driven in a large part by the highly conserved IGF/Akt/FOXO pathway, where depleted nutrient levels result in activation of FOXO, a transcription factor with many autophagy-related gene targets. Conclusion:  Reconstruction of these gene networks and pathways in amphioxus muscle provides a key point of comparison between the distantly related groups assessed thus far, significantly refining the reconstruction of the ancestral state for chordate myoblast fusion genes and identifying the extensive role of duplicated genes in the IGF/Akt/FOXO pathway across animals. Our study elucidates the evolutionary trajectory of muscle genes as they relate to the increased complexity of vertebrate muscles and muscle development.Publisher PDFPeer reviewe

Genome of the rams horn snail Biomphalaria straminea : an obligate intermediate host of schistosomiasis

This work was supported by the Hong Kong Research Grant Council Collaborative Research Fund (C4015-20EF), General Research Fund (14100919), NSFC/RGC Joint Research Scheme (N_CUHK401/21), and The Chinese University of Hong Kong Direct Grant (4053433, 4053489). Y.Y., W.L.S., C.F.W., S.T.S.L., and Y.L. were supported by the Ph.D. studentships of The Chinese University of Hong Kong. A.H. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/N020146/1). T.B. is supported by a studentship from the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1). M.E.A.R. is supported by a Ph.D. studentship from the School of Biology and St Andrews University.Background: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. Findings: Using a combination of Illumina short‐read, 10X Genomics linked‐read, and Hi‐C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. Conclusion: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.Publisher PDFPeer reviewe

Gene and genome duplication in animal evolution

Gene and genome duplications have an important role in evolution as a mechanism that creates novel genetic material. Paralogues created by duplication can diversify in function and contribute to the complexity of genetic networks, especially in the context of the gene regulation and signalling pathways that control animal development. Clusters of related genes that have arisen by tandem duplication illustrate the role of regulatory elements in preserving synteny by constraining gene neighbourhoods. Whole genome duplications have occurred on the stems of lineages characterised by the evolution of novel structures, adaptations to different environments, and species diversity. Here, I aim to understand how gene and genome duplications have impacted specific developmental gene families and processes throughout animal evolution with a comparative genomics approach. I make use of genomic resources from phylogenetically informative lineages, including new genomes of early-branching chordates, spiralians, and ecdysozoans. I have examined the impact of the vertebrate two rounds of whole genome duplication on chordate muscle development including the highly conserved family of myogenic regulatory factors and muscle gene expression. I have also investigated the evolution of homeobox gene families, with a focus on clusters of genes found across bilaterians, and specifically focus on the Hox cluster. With phylogenetic and synteny analyses, I found that a tandem duplication underpins the origin of two vertebrate muscle gene types. I examined the impact of whole genome duplication on a diversity of genes encoding proteins in a highly conserved signalling pathway in muscle, and I surveyed and revised the hypotheses for the evolution of homeobox genes across the bilaterians. In doing so, I have also generated a large resource of genomic annotations and protein sequences to facilitate functional studies in the future. These findings not only have identified certain duplications that have underpinned certain known instances of subfunctionalisation among paralogues, but also indicate gene families to target for future study