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

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Extensive chordate and annelid macrosynteny reveals ancestral homeobox gene organization

Genes with the homeobox motif are crucial in developmental biology and widely implicated in the evolution of development. The Antennapedia (ANTP)-class is one of the two major classes of animal homeobox genes, and includes the Hox genes, renowned for their role in patterning the anterior–posterior axis of animals. The origin and evolution of the ANTP-class genes are a matter of some debate. A principal guiding hypothesis has been the existence of an ancient gene Mega-cluster deep in animal ancestry. This hypothesis was largely established from linkage data from chordates, and the Mega-cluster hypothesis remains to be seriously tested in protostomes. We have thus mapped ANTP-class homeobox genes to the chromosome level in a lophotrochozoan protostome. Our comparison of gene organization in Platynereis dumerilii and chordates indicates that the Mega-cluster, if it did exist, had already been broken up onto four chromosomes by the time of the protostome–deuterostome ancestor (PDA). These results not only elucidate an aspect of the genome organization of the PDA but also reveal high levels of macrosynteny between P. dumerilii and chordates. This implies a very low rate of interchromosomal genome rearrangement in the lineages leading to P. dumerilii and the chordate ancestor since the time of the PDA

Nuclear genomes of Birgus latro, Paralithodes camtschaticus, and Panulirus ornatus

This dataset contains curated genomes (with soft-masked repetitive elements) of three decapods. The organisms are: the coconut crab (Birgus latro), the red king crab (Paralithodes camtschaticus), and the ornate spiny lobster (Panulirus ornatus). The genomes were assembled during a study of terrestrialism in the Anomura and are the first draft assemblies of the nuclear genomes of each of the three organisms. The accompanying raw annotation files were generated using RNA-seq hints

Terpenes and Terpenoids in Plants: Interactions with Environment and Insects

The interactions of plants with environment and insects are bi-directional and dynamic. Consequently, a myriad of mechanisms has evolved to engage organisms in different types of interactions. These interactions can be mediated by allelochemicals known as volatile organic compounds (VOCs) which include volatile terpenes (VTs). The emission of VTs provides a way for plants to communicate with the environment, including neighboring plants, beneficiaries (e.g., pollinators, seed dispersers), predators, parasitoids, and herbivores, by sending enticing or deterring signals. Understanding terpenoid distribution, biogenesis, and function provides an opportunity for the design and implementation of effective and efficient environmental calamity and pest management strategies. This review provides an overview of plant–environment and plant–insect interactions in the context of terpenes and terpenoids as important chemical mediators of these abiotic and biotic interactions

Identification of putative ecdysteroid and juvenile hormone pathway genes in the shrimp Neocaridina denticulata

© 2014 Elsevier Inc. Although the sesquiterpenoid juvenile hormone (JH) and the steroidal ecdysteroids are of vital importance to the development and reproduction of insects, our understanding of the evolution of these crucial hormonal regulators in other arthropods is limited. To better understand arthropod hormone evolution and regulation, here we describe the hormonal pathway genes (e.g. those involved in hormone biosynthesis, degradation, regulation and signal transduction) of a new decapod model, the shrimp Neocaridina denticulata. The majority of known insect sesquiterpenoid and ecdysteroid pathway genes and their regulators are contained in the N. denticulata genome. In the sesquiterpenoi d pathway, these include biosynthetic pathway components: juvenile hormone acid methyltransferase (JHAMT); hormone binding protein: juvenile hormone binding protein (JHBP); and degradation pathway components: juvenile hormone esterase (JHE), juvenile hormone esterase binding protein (JHEBP) and juvenile hormone epoxide hydrolase (JHEH), with the JHBP, JHEBP and JHEH genes being discovered in a crustacean for the first time here. Ecdysteroid biosynthetic pathway genes identified include spook, phantom, disembodied, shadow and CYP18. Potential hormonal regulators and signal transducers such as allatostatins (ASTs), Methoprene-tolerant (Met), Retinoid X receptor (RXR), Ecdysone receptor (EcR), calponin-like protein Chd64, FK509-binding protein (FKBP39), Broad-complex (Br-c), and crustacean hyperglycemic hormone/molt-inhibiting hormone/gonad-inhibiting hormone (CHH/MIH/GIH) genes are all present in the shrimp N. denticulata. To our knowledge, this is the first report of these hormonal pathways and their regulatory genes together in a single decapod, providing a vital resource for further research into development, reproduction, endocrinology and evolution of crustaceans, and arthropods in general.Link_to_subscribed_fulltex