Genomic signatures of isolation, hybridization, and selection during speciation of island finches

Sister species occurring sympatrically on islands are rare and offer unique opportunities to understand how speciation can proceed in the face of gene flow. The São Tomé grosbeak is a massive-billed, 'giant' finch endemic to the island of São Tomé in the Gulf of Guinea, where it has diverged from its co-occurring sister species the Príncipe seedeater, an average-sized finch that also inhabits two neighbouring islands. Here, we show that the grosbeak carries a large number of unique alleles different from all three Príncipe seedeater populations, but also shares many alleles with the sympatric São Tomé population of the seedeater, a genomic signature signifying divergence in isolation as well as subsequent introgressive hybridization. Furthermore, genomic segments that remain unique to the grosbeak are situated close to genes, including genes that determine bill morphology, suggesting the preservation of adaptive variation through natural selection during divergence with gene flow. This study reveals a complex speciation process whereby genetic drift, introgression, and selection during periods of isolation and secondary contact all have shaped the diverging genomes of these sympatric island endemic finches.

Genomic and Metabolomic Analyses of the Marine Fungus Emericellopsis cladophorae: Insights into Saltwater Adaptability Mechanisms and Its Biosynthetic Potential

The genus Emericellopsis is found in terrestrial, but mainly in marine, environments with a worldwide distribution. Although Emericellopsis has been recognized as an important source of bioactive compounds, the range of metabolites expressed by the species of this genus, as well as the genes involved in their production are still poorly known. Untargeted metabolomics, using UPLC- QToF–MS/MS, and genome sequencing (Illumina HiSeq) was performed to unlock E. cladophorae MUM 19.33 chemical diversity. The genome of E. cladophorae is 26.9 Mb and encodes 8572 genes. A large set of genes encoding carbohydrate-active enzymes (CAZymes), secreted proteins, transporters, and secondary metabolite biosynthetic gene clusters were identified. Our analysis also revealed genomic signatures that may reflect a certain fungal adaptability to the marine environment, such as genes encoding for (1) the high-osmolarity glycerol pathway; (2) osmolytes’ biosynthetic processes; (3) ion transport systems, and (4) CAZymes classes allowing the utilization of marine polysaccharides. The fungal crude extract library constructed revealed a promising source of antifungal (e.g., 9,12,13-Trihydroxyoctadec-10-enoic acid, hymeglusin), antibacterial (e.g., NovobiocinA), anticancer (e.g., daunomycinone, isoreserpin, flavopiridol), and anti-inflammatory (e.g., 2’-O-Galloylhyperin) metabolites. We also detected unknown compounds with no structural match in the databases used. The metabolites’ profiles of E. cladophorae MUM 19.33 fermentations were salt dependent. The results of this study contribute to unravel aspects of the biology and ecology of this marine fungus. The genome and metabolome data are relevant for future biotechnological exploitation of the species.

Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.

Genomic diversification of long polynucleotide fragments is a signature of emerging SARS-CoV-2 variants of concern

Highly transmissible or immuno-evasive SARS-CoV-2 variants have intermittently emerged and outcompeted previously circulating strains, resulting in repeated COVID-19 surges, reinfections, and breakthrough infections in vaccinated individuals. With over 5 million SARS-CoV-2 genomes sequenced globally over the last 2 years, there is unprecedented data to decipher how competitive viral evolution results in the emergence of fitter SARS-CoV-2 variants. Much attention has been directed to studying how specific mutations in the Spike protein impact its binding to the ACE2 receptor or viral neutralization by antibodies, but there is limited knowledge of genomic signatures shared primarily by dominant variants. Here we introduce a methodology to quantify the genome-wide distinctiveness of polynucleotide fragments of various lengths (3- to 240-mers) that constitute SARS-CoV-2 lineage genomes. Compared to standard phylogenetic distance metrics and overall mutational load, the quantification of distinctive 9-mer polynucleotides provides a higher resolution of separation between variants of concern (Reference = 89, IQR: 65-108; Alpha = 166, IQR: 150-182; Beta 130, IQR: 113-147; Gamma = 165, IQR: 152-180; Delta = 234, IQR: 216-253; and Omicron = 294, IQR: 287-315). The similar scoring of the Alpha and Gamma variants by our methodology is consistent with these strains emerging at approximately the same time and circulating in distinct geographical regions as dominant strains. Furthermore, evaluation of genomic distinctiveness for 1,363 lineages annotated in GISAID highlights that polynucleotide diversity has increased over time (R2 = 0.37) and that VOCs show high distinctiveness compared to non-VOC contemporary lineages. To facilitate similar real-time assessments on the competitive fitness potential of future variants, we are launching a freely accessible resource for infusing pandemic preparedness with genomic inference ("GENI" — https://academia.nferx.com/GENI). This study demonstrates the value of characterizing new SARS-CoV-2 variants by their genome-wide polynucleotide distinctiveness and emphasizes the need to go beyond a narrow set of mutations at known functionally salient sites.

binny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms existing state-of-the-art binning methods and finds unique genomes that could not be detected by other methods. binny uses k-mer-composition and coverage by metagenomic reads for iterative, non-linear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets. When compared to five widely used binning algorithms, binny recovers the most near-complete (>95% pure, >90% complete) and high-quality (>90% pure, >70% complete) genomes from simulated data sets from the Critical Assessment of Metagenome Interpretation (CAMI) initiative, as well as from a real-world benchmark comprised of metagenomes from various environments. binny is implemented as Snakemake workflow and available from https://github.com/a-h-b/binny.

Genomic signatures of desert adaptation at gene-rich regions in zebu cattle from the African drylands

Sudan, the largest country in Africa, acts as a corridor between North and sub-Saharan Africa along the river Niles. It comprises warm arid and semi-arid grazing lands, and it is home to the second-largest African population of indigenous livestock. Indigenous Sudanese cattle are mainly indicine/zebu (humped) type. They thrive in the harshest dryland environments characterised by high temperatures, long seasonal dry periods, nutritional shortages, and vector diseases challenges. We investigated genome diversity in six indigenous African zebu breeds sampled in Sudan (Aryashai, Baggara, Butana, Fulani, Gash, and Kenana). We adopted three genomic scan approaches to identify candidate selective sweeps regions (ZHp, FST, XP-EHH). We identified a set of gene-rich selective sweep regions shared across African and Asian zebu or unique to Sudanese zebu. In particular, African and Asian zebu candidate gene-rich regions are detected on chromosomes 2, 5 and 7. They include genes involved in immune response, body size and conformation, and stress response to heat. In addition, a 250 kb selective sweep on chromosome 16 was detected exclusively in five Sudanese zebu populations. This region spans seven genes, including PLCH2, PEX10, PRKCZ and SKI, which are involved in alternative adaptive metabolic strategies of insulin signalling, glucose homeostasis, and fat metabolism. Together, these genes may contribute to the zebu cattle resilience to heat, nutritional and water shortages. Our results highlight the putative importance of selection at gene-rich genome regions, which might be under a common regulatory genetic control, as an evolutionary mechanism for rapid adaptation to the complexity of environmental challenges.

Clinical and genomic signatures of rising SARS-CoV-2 Delta breakthrough infections in New York

In 2021, Delta has become the predominant SARS-CoV-2 variant worldwide. While vaccines effectively prevent COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occur. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contribute to increased rates of breakthrough infections compared to unvaccinated controls. Here, we show a steep and near complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25, its spike mutation S112L, and nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthroughs increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. Our data indicate a limited impact of vaccine escape in favor of Delta’s increased epidemic growth in times of waning vaccine protection.

Genetic Relationships and Genome Selection Signatures Between Soybean Cultivars from Brazil and United States After Decades of Breeding

Soybeans are one of the most important crops worldwide. Brazil and the United States (US) are the world’s two biggest producers of this legume. The increase of publicly available DNA sequencing data as well as high-density genotyping data of multiple soybean germplasms has made it possible to understand the genetic relationships and identify genomics regions that underwent selection pressure during soy domestication and breeding. In this study, we analyzed the genetic relationships between Brazilian (N=235) and US soybean cultivars (N=675) released in different decades, and screened for genomic signatures between Brazilian and US cultivars. The population structure analysis demonstrated that the Brazilian germplasm has a narrower genetic base than the US germplasm. The US cultivars was grouped according to the maturity groups, while Brazilian cultivars were separated according to decades of releases. We found 73 SNPs that differentiate Brazilian and US soybean germplasm. Maturity-associated SNPs showed high allelic frequency differences between Brazil and US accessions. Other important loci were identified separating cultivars released before and after 1996 in Brazil. Our data showed important genomic regions under selection during decades of soybean breeding in Brazil and the US that should be targeted to adapt lines from different origins in these countries.

Genomic signatures and insights into host niche adaptation of the entomopathogenic fungus Metarhizium humberi

The genus Metarhizium is composed of species used in biological control programes of agricultural pests worldwide. This genus includes common fungal pathogen of many insects and mites and endophytes that can increase plant growth. Metarhizium humberi was recently described as a new species. This species is highly virulent against some insect pests and promotes growth in sugarcane, strawberry, and soybean crops. In the present study, we sequenced the genome of M. humberi, isolate ESALQ1638, and performed a functional analysis to determine its genomic signatures and highlight the genes and biological processes associated with its lifestyle. The genome annotation predicted 10633 genes in M. humberi, of which 92.0% are assigned putative functions, and ∼17% of the genome was annotated as repetitive sequences. We found that 18.5% of the M. humberi genome is similar to experimentally validated proteins associated with pathogen-host interaction. Compared to the genomes of eight Metarhizium species, the M. humberi ESALQ1638 genome revealed some unique traits that stood out, e.g.,, more genes functionally annotated as polyketide synthases (PKs), overrepresended GO-terms associated to transport of ions, organic and amino acid, a higher percentage of repetitive elements, and higher levels of RIP-induced point mutations. The M. humberi genome will serve as a resource for promoting studies on genome structure and evolution that can contribute to research on biological control and plant biostimulation. Thus, the genomic data supported the broad host range of this species within the generalist PARB clade and suggested that M. humberi ESALQ1638 might be particularly good at producing secondary metabolites and might be more efficient in transporting amino acids an organics compounds.

Genomic signatures of pre-resistance in Mycobacterium tuberculosis

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.