Biology subjects

Irwin, D. M.

Publications and source records attributed to Irwin, D. M..

6 recordsLinked to original sources

bioRxiv2024

Identification and genomic characterization of a novel bisegmented coronavirus in the lesser panda

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses and are renowned for their capacity to infect a diverse range of animals, including humans. In this study, we report the identification and characterization of a novel bisegmented coronavirus, designated LpCoV, from a dead lesser panda, which exhibited severe clinical manifestations and lesions in multiple organs. The LpCoV represents the first documented coronavirus with a unique bisegmented genome while maintaining the typical coronavirus morphology. One genomic segment encodes the ORF1ab polyprotein, while the other segment encodes the spike and nucleocapsid proteins, notably lacking the envelope (E) and membrane (M) genes. The pairwise patristic distances of the five concatenated domains in the replicase region (3CLpro, NiRAN, RdRP, ZBD, and HEL1) between LpCoV and -{delta} coronaviruses range from 1.19 to 1.70. Based on the classification criteria established by the International Committee on Taxonomy of Viruses (ICTV), LpCoV is proposed to constitute a new genus within the Coronaviridae family. An epidemiological investigation identified five LpCoV-like viruses in lesser pandas from two different provinces (Sichuan and Jiangsu) indicating the long-term circulation and expansion of bisegmented coronaviruses in wildlife. These findings highlight the imperative for comprehensive viral surveillance in wildlife, which is essential for understanding and mitigating the risk of animal diseases and zoonotic spillover.

microbiology↗

bioRxiv2022

Multiple omic investigations of freeze tolerance adaptation in the aquatic ectothermic vertebrate, the Amur sleeper

Freeze tolerance is an amazing overwintering strategy that enables ectotherms to occupy new niches and survive in cold climates. However, the genetic basis underpinning this ecologically relevant adaptation is largely unknown. Amur sleeper is the only known freeze-tolerant fish species that can overwinter with its entire body frozen in ice. Here, we sequenced the chromosome-level genome of the Amur sleeper and performed comparative genomic, transcriptomic, and metabolomic analyses to investigate this remarkable adaptation. Phylogenetic analyses showed that the Amur sleeper diverged from its close relative with no cold hardiness about 15.07 million years ago and revealed two unusual population expansions during the glacial epochs. Integrative omics data identified a synchronous regulation of genes and metabolites involved in hypometabolism and cellular stress response, and several related genes showed strong evidence of accelerated evolution and positive selection. Potential evolutionary innovations that might aid in freezing survival were found to be associated with the dynamic rearrangement of the cytoskeleton to maintain cell viability, redistribution of water and cryoprotectants to limit cell volume reduction, and inhibition in nerve activity to facilitate dormancy, demonstrating a coordinated evolution for this complex adaptation. Overall, our work provides valuable resources and opportunities to unveil the genetic basis of freeze tolerance adaptation in ectothermic vertebrates.

evolutionary biology↗

bioRxiv2021

Single-cell RNA-sequencing reveals thoracolumbar vertebra heterogeneity and rib-genesis in pigs

Thoracolumbar vertebra (TLV) and rib primordium (RP) development is a common evolutionary feature across vertebrates although whole-organism analysis of TLV and RP gene expression dynamics has been lacking. Here we investigated the single-cell transcriptomic landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene-expression signatures. In-depth dissection of the gene-expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and rib development. Further analysis of cell-type-specific and strand-specific expression uncovered the extremely high levels of HOXA10 3-UTR sequence specific to osteoblast of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell-type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

developmental biology↗

bioRxiv2020

Worldwide tracing of mutations and the evolutionary dynamics of SARS-CoV-2

Understanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.

microbiology↗

bioRxiv2019

Convergent genomic signatures of high altitude adaptation among domestic mammals

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we utilized 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provides insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

evolutionary biology↗

bioRxiv2016

Evolutionary history of the brown rat: out of southern East Asia and selection

The brown rat (Rattus norvegicus) is found wherever humans live and transmits many diseases, and its breeding produced the laboratory rat used widely in medical research. Here, we sequenced whole genomes from 118 rats to explore the origin and dispersal routes of the brown rat and the domestication of the laboratory rat. We showed that brown rats migrated about 3600 years ago from southern East Asia, rather than Northern Asia as formerly suggested, to the Middle East and then to Europe and Africa. Many genes involved in the immune system experienced positive selection in the wild brown rat, while genes involved in the nervous system and energy metabolism showed evidence of artificial selection during the domestication of laboratory strains. Our findings demystify the puzzling origin and migration of brown rats and reveal the impact of evolution and domestication on this animal.

evolutionary biology↗