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1.
Nature ; 563(7732): 501-507, 2018 11.
Article in English | MEDLINE | ID: mdl-30429615

ABSTRACT

Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.


Subject(s)
Aedes/genetics , Arbovirus Infections/virology , Arboviruses , Genome, Insect/genetics , Genomics/standards , Insect Control , Mosquito Vectors/genetics , Mosquito Vectors/virology , Aedes/virology , Animals , Arbovirus Infections/transmission , Arboviruses/isolation & purification , DNA Copy Number Variations/genetics , Dengue Virus/isolation & purification , Female , Genetic Variation/genetics , Genetics, Population , Glutathione Transferase/genetics , Insecticide Resistance/drug effects , Male , Molecular Sequence Annotation , Multigene Family/genetics , Pyrethrins/pharmacology , Reference Standards , Sex Determination Processes/genetics
2.
Nucleic Acids Res ; 47(8): 4198-4210, 2019 05 07.
Article in English | MEDLINE | ID: mdl-30805621

ABSTRACT

The ribosome exit tunnel is an important structure involved in the regulation of translation and other essential functions such as protein folding. By comparing 20 recently obtained cryo-EM and X-ray crystallography structures of the ribosome from all three domains of life, we here characterize the key similarities and differences of the tunnel across species. We first show that a hierarchical clustering of tunnel shapes closely reflects the species phylogeny. Then, by analyzing the ribosomal RNAs and proteins, we explain the observed geometric variations and show direct association between the conservations of the geometry, structure and sequence. We find that the tunnel is more conserved in the upper part close to the polypeptide transferase center, while in the lower part, it is substantially narrower in eukaryotes than in bacteria. Furthermore, we provide evidence for the existence of a second constriction site in eukaryotic exit tunnels. Overall, these results have several evolutionary and functional implications, which explain certain differences between eukaryotes and prokaryotes in their translation mechanisms. In particular, they suggest that major co-translational functions of bacterial tunnels were externalized in eukaryotes, while reducing the tunnel size provided some other advantages, such as facilitating the nascent chain elongation and enabling antibiotic resistance.


Subject(s)
Archaea/genetics , Bacteria/genetics , Eukaryota/genetics , Protein Biosynthesis , RNA, Ribosomal/chemistry , Ribosomal Proteins/chemistry , Ribosomes/ultrastructure , Amino Acid Sequence , Archaea/classification , Archaea/metabolism , Bacteria/classification , Bacteria/metabolism , Cryoelectron Microscopy , Crystallography, X-Ray , Eukaryota/classification , Eukaryota/metabolism , Nucleic Acid Conformation , Phylogeny , Protein Folding , Protein Structure, Secondary , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Ribosomes/classification , Ribosomes/genetics , Ribosomes/metabolism , Sequence Alignment , Sequence Homology, Amino Acid
3.
Nat Commun ; 15(1): 579, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233380

ABSTRACT

Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.


Subject(s)
Chromatin , Evolution, Molecular , Animals , Chromatin/genetics , Genome/genetics , Anura/genetics , Xenopus/genetics , Centromere/genetics
4.
Science ; 356(6333): 92-95, 2017 04 07.
Article in English | MEDLINE | ID: mdl-28336562

ABSTRACT

The Zika outbreak, spread by the Aedes aegypti mosquito, highlights the need to create high-quality assemblies of large genomes in a rapid and cost-effective way. Here we combine Hi-C data with existing draft assemblies to generate chromosome-length scaffolds. We validate this method by assembling a human genome, de novo, from short reads alone (67× coverage). We then combine our method with draft sequences to create genome assemblies of the mosquito disease vectors Aeaegypti and Culex quinquefasciatus, each consisting of three scaffolds corresponding to the three chromosomes in each species. These assemblies indicate that almost all genomic rearrangements among these species occur within, rather than between, chromosome arms. The genome assembly procedure we describe is fast, inexpensive, and accurate, and can be applied to many species.


Subject(s)
Aedes/genetics , Contig Mapping/methods , Genome, Insect , Animals , Conserved Sequence , Culex/genetics , Gene Rearrangement , Humans , Nucleic Acid Conformation
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