PaperPlayer biorxiv genomics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.30.229872v1?rss=1

Authors: Etebari, K., Hereward, J., Sailo, A., Ahoafi, E. M., Tautua, R., Tsatsia, H., Jackson, G. V., Furlong, M. J.

Abstract:

Incursions of the Coconut rhinoceros beetle (CRB), Oryctes rhinoceros, have been detected in several countries of the south-west Pacific in recent years, resulting in an expansion of the pest's geographic range. It has been suggested that this resurgence is related to an O. rhinoceros mitochondrial lineage (previously referred to as the CRB-G biotype) that is reported to show reduced susceptibility to the well-established classical biocontrol agent, Oryctes rhinoceros nudivirus (OrNV). We investigated O. rhinoceros population genetics and the OrNV status of adult specimens collected in the Philippines and seven different South Pacific island countries (Fiji, New Caledonia, Papua New Guinea (PNG), Samoa, Solomon Islands, Tonga, and Vanuatu). Based on the presence of single nucleotide polymorphisms (snps) in the mitochondrial Cytochrome C Oxidase subunit I (CoxI) gene, we found three major mitochondrial lineages (CRB-G, a PNG lineage (CRB-PNG) and the South Pacific lineage (CRB-S)) across the region. Haplotype diversity varied considerably between and within countries. The O. rhinoceros population in most countries was monotypic and all individuals tested belonged to a single mitochondrial lineage (Fiji, CRB-S; Tonga, CRB-S; Vanuatu, CRB-PNG; PNG (Kimbe), CRB-PNG; New Caledonia CRB-G; Philippines, CRB-G). However, in Samoa we detected CRB-S and CRB-PNG and in Solomon Islands we detected all three haplotype groups. Genotyping-by-Sequencing (GBS) methods were used to genotype 10,000 snps from 230 insects across the Pacific and showed genetic differentiation in the O. rhinoceros nuclear genome among different geographical populations. The GBS data also provided evidence for gene flow and admixture between different haplotypes in Solomon Islands. Therefore, contrary to earlier reports, CRB-G is not solely responsible for damage to the coconut palms reported since the pest was first recorded in Solomon Islands in 2015. We also PCR-screened a fragment of OrNV from 260 insects and detected an extremely high prevalence of viral infection in all three haplotypes in the region. We conclude that the haplotype groups CRB-G, CRB-S, and PNG, do not represent biotypes, subspecies, or cryptic species, but simply represent different invasions of O. rhinoceros across the Pacific. This has important implications for management, especially biological control, of Coconut rhinoceros beetle in the region.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.30.228320v1?rss=1

Authors: Techer, M. A., Roberts, J. M. K., Cartwright, R. A., Mikheyev, A. S.

Abstract:

Host switching allows parasites to expand their niches. However, successful switching may require suites of adaptations and may decrease performance on the old host. As a result, reductions in gene flow accompany many host switches, driving speciation. Because host switches tend to be rapid, it is difficult to study them in real time and their demographic parameters remain poorly understood. As a result, fundamental factors that control subsequent parasite evolution, such as the size of the switching population or the extent of immigration from the original host, remain largely unknown. To shed light on the host switching process, we explored how host switches occur in independent host shifts by two ectoparasitic honey bee mites (Varroa destructor and V. jacobsoni). Both switched to the western honey bee (Apis mellifera) after it was brought into contact with their ancestral host (Apis cerana), ~70 and ~12 years ago, respectively. Varroa destructor subsequently caused worldwide collapses of honey bee populations. Using whole-genome sequencing on 44 mites collected in their native ranges from both the ancestral and novel hosts, we were able to reconstruct the known temporal dynamics of the switch. We further found that hundreds of haploid genomes were involved in the initial host switch, and, despite being greatly reduced, some gene flow remains between mites adapted to different hosts remains. Our findings suggest that while reproductive isolation may facilitate fixation of traits beneficial for exploitation of the new host, ongoing genetic exchange may allow genetic amelioration of inbreeding effects.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.30.225821v1?rss=1

Authors: Senra, M., Fonseca, A. L.

Abstract:

Tyrosinases (EC 1.14.18.1) are type-3 copper metalloenzymes with strong oxidative capacities and low allosteric selectivity to phenolic and non-phenolic aromatic compounds that have been used as biosensors and biocatalysts to mitigate the impacts of environmental contaminants over aquatic ecosystems. However, the widespread use of these polyphenol oxidases is limited by elevated production costs and restricted knowledge on their spectrum of action. Here, six tyrosinase homologs were identified and characterized from the genomes of 4 widespread freshwater ciliates using bioinformatics. Binding energies between 3D models of these homologs and ~1000 contaminants of emerging concern (CECs), including fine chemicals, pharmaceuticals, personal care products, illicit drugs, natural toxins, and pesticides were estimated through virtual screening, suggesting their spectrum of action and potential uses in environmental biotechnology might be considerably broader than previously thought. Moreover, considering that many ciliates, including those caring tyrosinase genes within their genomes are fast-growing unicellular microeukaryotes that can be efficiently culturable at large-scales under in vitro conditions, should be regarded as potential low-cost sources for the production of relevant biotechnological molecules.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.31.231761v1?rss=1

Authors: Halo, J., Pendelton, A. L., Shen, F., Doucet, A. J., Derrien, T., Hitte, C., Kirby, L. E., Myers, B., Sliwerska, E., Emery, S., Moran, J. V., Boyko, A., Kidd, J. M.

Abstract:

Technological advances have allowed improvements in genome reference sequence assemblies. Here, we combined long- and short-read sequence resources to assemble the genome of a female Great Dane dog. This assembly has improved continuity compared to the existing Boxer-derived (CanFam3.1) reference genome. Annotation of the Great Dane assembly identified 22,182 protein-coding gene models and 7,049 long non-coding RNAs, including 49 protein-coding genes not present in the CanFam3.1 reference. The Great Dane assembly spans the majority of sequence gaps in the CanFam3.1 reference and illustrates that 2,151 gaps overlap the transcription start site of a predicted protein-coding gene. Moreover, a subset of the resolved gaps, which have an 80.95% median GC content, localize to transcription start sites and recombination hotspots more often than expected by chance, suggesting the stable canine recombinational landscape has shaped genome architecture. Alignment of the Great Dane and CanFam3.1 assemblies identified 16,834 deletions and 15,621 insertions, as well as 2,665 deletions and 3,493 insertions located on secondary contigs. These structural variants are dominated by retrotransposon insertion/deletion polymorphisms and include 16,221 dimorphic canine short interspersed elements (SINECs) and 1,121 dimorphic long interspersed element-1 sequences (LINE-1_Cfs). Analysis of sequences flanking the 3'-end of LINE-1_Cfs (i.e., LINE-1_Cf 3'-transductions) suggests multiple retrotransposition-competent LINE-1_Cfs segregate among dog populations. Consistent with this conclusion, we demonstrate that a canine LINE-1_Cf element with intact open reading frames can retrotranspose its own RNA and that of a SINEC_Cf consensus sequence in cultured human cells, implicating ongoing retrotransposon activity as a driver of canine genetic variation.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.31.231522v1?rss=1

Authors: Housman, G., Quillen, E. E., Stone, A. C.

Abstract:

Objective: Epigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations. Methods: Genome-wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip. Results: Several significantly differentially methylated positions (DMPs) and regions (DMRs) were found between tissue types. Substantial OA-related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA-related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA-related methylation patterns in primates. Conclusions: Overall, these findings reinforce current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This work further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.31.231498v1?rss=1

Authors: Lai, E., Joseph, B.

Abstract:

Accurate splice site selection is critical for fruitful gene expression. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic splice sites (SS), even though majority of these bear weak splicing motifs and appear incompetent. Mechanistically, the EJC directly conceals splicing elements through position-specific recruitment, preventing SS definition. We note that intron removal using strong, canonical SS yields AG|GU signatures at exon-exon junctions. Unexpectedly, we discover that scores of these minimal exon junction sequences are in fact EJC-suppressed 5' and 3' recursive SS, and that loss of EJC regulation from such transcripts triggers faulty mRNA resplicing. An important corollary is that intronless cDNA expression constructs from aforementioned targets yield high levels of unanticipated, truncated transcripts generated by resplicing. Consequently, we conclude the EJC has ancestral roles to defend transcriptome fidelity by (1) repressing illegitimate splice sites on pre-mRNAs, and (2) preventing inadvertent activation of such sites on spliced segments.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.30.228460v1?rss=1

Authors: Paul, D., Jani, K., Kumar, J., Chauhan, R., Seshadri, V., Lal, G., Karyakarte, R., Joshi, S., Tambe, M., Sen, S., Karade, S., Anand, K. B., Shergill, S. P. S., Gupta, R. M., Bhat, M. K., Sahu, A., Shouche, Y. S.

Abstract:

India has become the third worst-hit nation by the COVID-19 pandemic caused by the SARS-CoV-2 virus. Here, we investigated the molecular, phylogenomic, and evolutionary dynamics of SARS-CoV-2 in western India, the most affected region of the country. A total of 90 genomes were sequenced. Four nucleotide variants, namely C241T, C3037T, C14408T (Pro4715Leu), and A23403G (Asp614Gly), located at 5'UTR, Orf1a, Orf1b, and Spike protein regions of the genome, respectively, were predominant and ubiquitous (90%). Phylogenetic analysis of the genomes revealed four distinct clusters, formed owing to different variants. The major cluster (cluster 4) is distinguished by mutations C313T, C5700A, G28881A are unique patterns and observed in 45% of samples. We thus report a newly emerging pattern of linked mutations. The predominance of these linked mutations suggests that they are likely a part of the viral fitness landscape. A novel and distinct pattern of mutations in the viral strains of each of the districts was observed. The Satara district viral strains showed mutations primarily at the 3' end of the genome, while Nashik district viral strains displayed mutations at the 5' end of the genome. Characterization of Pune strains showed that a novel variant has overtaken the other strains. Examination of the frequency of three mutations i.e., C313T, C5700A, G28881A in symptomatic versus asymptomatic patients indicated an increased occurrence in symptomatic cases, which is more prominent in females. The age-wise specific pattern of mutation is observed. Mutations C18877T, G20326A, G24794T, G25563T, G26152T, and C26735T are found in more than 30% study samples in the age group of 10-25. Intriguingly, these mutations are not detected in the higher age range 61-80. These findings portray the prevalence of unique linked mutations in SARS-CoV-2 in western India and their prevalence in symptomatic patients.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.30.228122v1?rss=1

Authors: Han, Y., Nikolic, M., Gobs, M., Franzen, J., de Haan, G., Geiger, H., Wagner, W.

Abstract:

Age-associated DNA methylation reflects aspects of biological aging - therefore epigenetic clocks for mice can help to elucidate the impact of treatments or genetic background on the aging process in this model organism. Initially, age-predictors for mice were trained on genome-wide DNA methylation profiles, whereas we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three CG dinucleotides (CpGs). Here, we have re-evaluated pyrosequencing approaches in comparison to droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CpGs the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified in murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the epigenetic age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe further optimized and alternative targeted methods to determine epigenetic clocks in mice.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.29.227637v1?rss=1

Authors: Bikel, S., Gamaliel Lopez-Leal, G., Cornejo-Granados, F., Gallardo-Becerra, L., Sanchez, F., Equihua-Medina, E., Ochoa-Romo, J. P., Lopez-Contreras, B. E., Canizales-Quinteros, S., Ochoa-Leyva, A.

Abstract:

Changes in the composition of the human gut microbiome are recognized to have a significant association with obesity and metabolic syndrome. Mexico leads worldwide childhood-obesity rankings representing an epidemic problem for public health. To this date, it is still unclear how the gut phageome, the bacteriophage component of the virome, influences childhood obesity and obesity with metabolic syndrome. We characterized the gut phageome of 28 school-age children with healthy normal-weight (NW), obese (O), and obese with metabolic syndrome (OMS) profiles, using metagenomic sequencing of virus-like particles (VLPs) from fecal samples. Viromes derived from VLPs were mainly dominated by Caudovirales, and only Inoviridae family was significantly increased in obesity. The three groups showed a similar number of VLPs, while a significant increase in phage richness and diversity was found in obesity groups compared NW. Few phage contigs dominated the phageome composition in NW, being increased in obesity groups. Interestingly, the majority of the phageome was shared among all individuals, establishing a core and common phageome, which abundances correlated with anthropometric and biochemical traits and bacteria previously associated with obesity and metabolic syndrome. We also established a healthy core phageome shared in >80% of NW samples, with a decreased prevalence in the O and OMS groups. Our data support that changes in the gut phageome may contribute to obesity and metabolic syndrome development via bacterial dysbiosis. We consider the phageome characterization provides the basis for novel diagnostic and therapeutic strategies for managing obesity and preventing metabolic syndrome development in obese children through potential phage manipulation. To the best of our knowledge, this study represents the most in-depth sequenced dataset of human bacteriophages, demonstrating for the first time that alterations of the gut phageome characterize obesity.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.29.226373v1?rss=1

Authors: Lee, C. A., Abd-Rabbo, D., Reimand, J.

Abstract:

Localised variation of somatic mutation rates affects diverse functional sequence elements in cancer genomes through poorly understood mutational processes. Here, we characterise the mutational landscape of 640,000 gene regulatory and chromatin architectural elements in 2,421 whole cancer genomes using our new statistical model RM2. This method quantifies differential mutation rates and signatures in classes of genomic elements via genetic, trinucleotide and megabase-scale effects. We report a detailed map of localised mutational processes affecting CTCF binding sites, transcription start sites (TSS) and cancer-specific open-chromatin regions. This includes a pan-cancer indel depletion in open-chromatin sites, a TSS-specific mutational process correlated with mRNA abundance in core cellular and cancer-associated processes, a subset of hypermutated, constitutively active CTCF binding sites involved in chromatin architectural interactions, and an enrichment of signature SBS17b in CTCF sites in gastrointestinal cancers. We also detect genetic driver alterations potentially underlying localised mutation rates, including RAD21 amplifications and BRAF mutations associating with mutagenesis of CTCF binding sites, and SDHA amplifications indicative of frequent lung cancer mutations in open-chromatin sites. Our framework and the catalogue of localised mutational processes provide novel perspectives to cancer genome evolution and its implications for oncogenesis, tumor heterogeneity and cancer driver gene discovery.

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