Project description:A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.
Project description:A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.
Project description:A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.
Project description:A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.
Project description:RNA sequencing (RNA-seq) has been a widely used high-throughput method to characterize transcriptomic dynamics spatiotemporally. However, typical RNA-seq data analysis pipelines depend on either a sequenced genome or reference transcripts. This constriction makes the use of RNA-seq for species lacking both of sequenced genomes and reference transcripts challenging. To solve this problem, we developed CRSP, an RNA-seq pipeline integrating multiple comparative species strategy but not depending on a specific sequenced genome or reference transcripts. Benchmarking suggests the CRSP tool can achieve high accuracy to quantify gene expression levels.
Project description:Venomous animals have traditionally been studied from a proteomic (but also transcriptomic) perspective, often overlooking the study of venom from a genomic point of view until recently. The rise of genomics has led to an increase in the number of reference genomes for non-model organisms, including venomous taxa, enabling new questions on venom evolution from a genomic context. Although venomous snakes are the fundamental model system in venom research, the number of high-quality reference genomes in the group remains limited. In this study, we present a high-quality chromosome-level reference genome for the Arabian horned viper (Cerastes gasperettii), a highly venomous snake native to the Arabian Peninsula. Our highly-contiguous genome allowed us to explore macrochromosomal rearrangements within the Viperidae family, as well as across squamate reptile evolution. Furthermore, we identified a total of ten different toxins conforming the venom’s core, in line with our proteomic results. We also compared microsyntenic changes in the main toxin gene clusters with those of other venomous snake species, highlighting the pivotal role of gene duplication and loss in the emergence and diversification of the two main toxin families for Cerastes gasperettii. Using Illumina data, we reconstructed the demographic history and genome-wide diversity of the species, revealing how historical aridity likely drove population expansions. Finally, this study highlights the importance of using long-read sequencing as well as chromosome-level reference genomes to disentangle the origin and diversification of toxin families in venomous species.
Project description:Venomous animals have traditionally been studied from a proteomic (but also transcriptomic) perspective, often overlooking the study of venom from a genomic point of view until recently. The rise of genomics has led to an increase in the number of reference genomes for non-model organisms, including venomous taxa, enabling new questions on venom evolution from a genomic context. Although venomous snakes are the fundamental model system in venom research, the number of high-quality reference genomes in the group remains limited. In this study, we present a high-quality chromosome-level reference genome for the Arabian horned viper (Cerastes gasperettii), a highly venomous snake native to the Arabian Peninsula. Our highly-contiguous genome allowed us to explore macrochromosomal rearrangements within the Viperidae family, as well as across squamate reptile evolution. Furthermore, we identified a total of ten different toxins conforming the venom’s core, in line with our proteomic results. We also compared microsyntenic changes in the main toxin gene clusters with those of other venomous snake species, highlighting the pivotal role of gene duplication and loss in the emergence and diversification of the two main toxin families for Cerastes gasperettii. Using Illumina data, we reconstructed the demographic history and genome-wide diversity of the species, revealing how historical aridity likely drove population expansions. Finally, this study highlights the importance of using long-read sequencing as well as chromosome-level reference genomes to disentangle the origin and diversification of toxin families in venomous species.
Project description:Genome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for studying DNA methylation in non-model organisms, we developed an integrated approach for studying DNA methylation differences without a reference genome. Experimentally, our method relies on an optimized 96-well protocol for reduced representation bisulfite sequencing (RRBS), which we have validated in nine species (human, mouse, rat, cow, dog, chicken, zebrafish, carp, and sea bass). Bioinformatically, we developed the RefFreeDMA software (http://RefFreeDMA.computational-epigenetics.org) to deduce ad hoc genomes directly from RRBS reads and to pinpoint differentially methylated regions. These regions are interpreted using motif enrichment analysis and/or cross-mapping to annotated genomes. We validated our method by reference-free analysis of cell type-specific DNA methylation in the blood of human, cow, and carp. In summary, we present a cost-effective method for epigenome analysis in ecology and evolution, which enables epigenome-wide association studies in natural populations and species without a reference genome.