Biology subjects

Gagnon, E.

Publications and source records attributed to Gagnon, E..

10 recordsLinked to original sources

bioRxiv2025

A new phylogeny and phylogenetic classification for Solanaceae

Solanaceae are a globally distributed family of considerable economic importance. Recent phylogenetic work on various clades in the family has resulted in a plethora of names at various taxonomic levels. This results in a confusing set of names applied to clades at different ranks, and to the use of informal names that are often not accepted in online resources. To solve this problem, we present here a phylogenetic classification following the PhyloCode for the Solanaceae. Traditional taxon names previously recognized at the ranks of tribe, genus, and section were maintained when associated with clades. We base our clade definitions on a newly constructed phylogeny of the family using 10 plastid and nuclear markers with a broad sampling of 1,474 species, roughly half of the diversity of the family. We complement this marker-based analysis with a phylogenomic analysis of 110 taxa (including 97 of the 102 genera in the family) using the Angiosperms353 probe set. This pair of analyses produced highly concordant phylogenies and provides strong support for the clades included in the classification. In total, we propose and define rank-free names for 38 major clades, including 16 infrageneric taxa within the mega-diverse Solanum. This rank-free system intends to promote name stability as new data become available, avoiding name changes to well-known groups.

evolutionary biology↗

bioRxiv2025

CD33 Epitope Editing Unlocks UM171-Expanded Cord Blood Grafts for AML Immunotherapy

Immunotherapies in acute myeloid leukemia (AML) are limited by shared antigen expression between leukemic and healthy hematopoietic cells, leading to on-target toxicity. Here we developed a clinically scalable strategy to engineer cord blood (CB)-derived hematopoietic stem and progenitor cell (HSPC) grafts resistant to CD33-directed therapies. Leveraging UM171-mediated expansion and adenine base editing, we precisely disrupted a critical epitope in CD33 required for gemtuzumab ozogamicin (GO) binding, centered on phenylalanine 21, while preserving CD33 expression and its sialic acid binding function. Ex vivo edited HSPCs maintained robust multilineage engraftment, T-cell output, and conferred protection from GO-induced myelotoxicity in xenograft models, without impairing anti-leukemic efficacy. Editing was efficient across multiple donors, enriched in primitive subsets, and exhibited minimal off-target activity by ultra-deep exome sequencing. Our work establishes base editor-driven epitope engineering as an improved approach to CD33-targeted immunotherapy-compatible HSPC grafts, enabling safe integration of currently available agents into post-transplant care.

immunology↗

bioRxiv2024

Solanum pan-genomics and pan-genetics reveal paralogs as contingencies in crop engineering

Pan-genomics and genome editing technologies are revolutionizing the breeding of globally cultivated crops. A transformative opportunity lies in the reciprocal exchange of genotype-to-phenotype knowledge of agricultural traits between these major crops and hundreds of locally cultivated indigenous crops, thereby enhancing the diversity and resilience of our food system. However, species-specific genetic variants and their interactions with desired natural or engineered mutations pose barriers to achieving predictable phenotypic effects, even between closely related crops or genotypes. Here, by establishing a pan-genome of the crop-rich genus Solanum and integrating functional genomics and genetics, we show that gene duplication and subsequent paralog diversification are a major obstacle to genotype-phenotype predictability. Despite broad conservation of gene macrosynteny among chromosome-scale references for 22 species, including 13 indigenous crops, hundreds of global and lineage-specific gene duplications exhibited dynamic evolutionary trajectories in paralog sequence, expression, and function, including among members of key domestication gene families. Extending our pan-genome with 10 cultivars of African eggplant and leveraging quantitative genetics and genome editing, we uncovered an intricate history of paralog emergence and evolution within this indigenous crop. The loss of an ancient redundant paralog of the classical regulator of stem cell proliferation and fruit organ number, CLAVATA3 (CLV3), was compensated by a lineage-specific tandem duplication. Subsequent pseudogenization of the derived copy followed by a cultivar-specific structural variant resulted in a single fused functional copy of CLV3 that modifies locule number alongside a newly identified gene controlling the same trait. Our findings demonstrate that paralog diversifications over short evolutionary periods are critical yet underexplored contingencies in trait evolvability and independent crop domestication histories. Unraveling these contingencies is crucial for translating genotype-to-phenotype relationships across related species.

genetics↗

bioRxiv2024

Convergent evolution of plant prickles is drivenby repeated gene co-option over deep time

An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. Here we genetically dissected repeated origins and losses of prickles, sharp epidermal projections, that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genus Solanum. Strikingly, homologs promote prickle formation across angiosperms that collectively diverged over 150 million years ago. By developing new Solanum genetic systems, we leveraged this discovery to eliminate prickles in a wild species and an indigenously foraged berry. Our findings implicate a shared hormone-activation genetic program underlying evolutionarily widespread and recurrent instances of plant morphological innovation.

evolutionary biology↗

bioRxiv2023

Contrasting patterns of presence-absence variation of NLRS within S. chilense are mainly shaped by past demographic history

Understanding the evolution of pathogen resistance genes (nucleotide-binding site-leucine-rich repeats, also known as NLRs) within a species requires a comprehensive examination of factors that affect gene loss and gain. We present a new reference genome of Solanum chilense, that leads to an increased number and more accurate annotation of NLRs. Next, using a target-capture approach, we quantify the presence-absence variation (PAV) of NLR loci across 20 populations from different habitats. We build a rigorous pipeline to validate the identification of PAV of NLRs, then show that PAV is larger within populations than between populations, suggesting that maintenance of NLR diversity is linked to population dynamics. Furthermore, the amount of PAV is not correlated with the NLR presence in gene clusters in the genome, but rather with the past demographic history of the species, with loss of NLRs in diverging populations at the distribution edges and smaller population sizes. Finally, using a redundancy analysis, we find limited evidence of PAV being linked to environmental gradients. Our results contradict the classic assumptions of the important selective role of PAV for NLRs, and suggest that NLRs PAV is driven by random processes (and weak selection) in an outcrossing plant with high nucleotide diversity.

evolutionary biology↗

bioRxiv2023

Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform.

The majority of cancer deaths are caused by solid tumors, where the four most prevalent cancers (breast, lung, colorectal and prostate) account for more than 60% of all cases (1). Tumor cell heterogeneity driven by variable cancer microenvironments, such as hypoxia, is a key determinant of therapeutic outcome. We developed a novel culture protocol, termed the Long-Term Hypoxia (LTHY) time course, to recapitulate the gradual development of severe hypoxia seen in vivo, to mimic conditions observed in primary tumors. Cells subjected to LTHY underwent a non-canonical epithelial to mesenchymal transition (EMT) based on miRNA and mRNA signatures as well as displayed EMT-like morphological changes. Concomitant to this, we report production of a novel truncated isoform of WT1 transcription factor (tWt1), a non-canonical EMT driver, with expression driven by a yet undescribed intronic promoter through hypoxia-responsive elements (HREs). We further demonstrated that tWt1 initiates translation from an intron-derived start codon, retains proper subcellular localization, DNA binding, and its human ortholog negatively predicts long-term patient survival. Our study demonstrates the importance of culture conditions that better mimic those observed in cancers, especially with regards to hypoxia, and identifies a novel isoform of WT1 which correlates with poor long-term survival in ovarian cancer.

molecular biology↗

bioRxiv2023

Morphological trait evolution in Solanum (Solanaceae): evolutionary lability of key taxonomic characters

Solanum L. is one of the worlds largest and economically most important plant genera, including 1,245 currently accepted species and several major and minor crops (e.g., tomato, potato, brinjal eggplant, scarlet eggplant, Gboma eggplant, lulo, and pepino). Here we provide an overview of the evolution of 25 key morphological traits for the major and minor clades of this giant genus based on stochastic mapping using a well-sampled recently published phylogeny of Solanum. The most evolutionarily labile traits (showing >150 transitions across the genus) relate to plant structure (growth form and sympodial unit structure), herbivore defence (glandular trichomes), pollination (corolla shape and colour), and dispersal (fruit colour). Ten further traits show evolutionary lability with 50-100 transitions across the genus (e.g., specialised underground organs, trichome structure, leaf type, inflorescence position and branching, stamen heteromorphism). Our results reveal a number of highly convergent traits in Solanum, including tubers, rhizomes, simple leaves, yellow corollas, heteromorphic anthers, dioecy, and dry fruits, and some unexpected pathways of trait evolution that could be explored in future studies. We show that informally named clades of Solanum can be morphologically defined by trait combinations providing a tool for identification and enabling predictive phylogenetic placement of unsampled species.

evolutionary biology↗

bioRxiv2021

Uncovering the Genetic Architecture of Broad Antisocial Behavior through a Genome-Wide Association Study Meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8,058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, P = 6.32 x 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). The SNP-based heritability of ASB was 8.4% (s.e.= 1.2%). Polygenic-risk-score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg{square}={square}0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg{square}={square}0.54), cognitive ability (intelligence rg= -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg={square}- 0.58, fathers age at death rg= -0.54). Our findings provide a starting point towards identifying critical biosocial risk mechanisms for the development of ASB.

genetics↗

bioRxiv2021

Phylogenomic data reveal hard polytomies across the backbone of the large genus Solanum (Solanaceae)

Premise of the studyEvolutionary studies require solid phylogenetic frameworks, but increased volumes of phylogenomic data have revealed incongruent topologies among gene trees in many organisms both between and within genomes. Some of these incongruences indicate polytomies that may remain impossible to resolve. Here we investigate the degree of gene-tree discordance in Solanum, one of the largest flowering plant genera that includes the cultivated potato, tomato, and eggplant, as well as 24 minor crop plants. MethodsA densely sampled species-level phylogeny of Solanum is built using unpublished and publicly available Sanger sequences comprising 60% of all accepted species (742 spp.) and nine regions (ITS, waxy, and seven plastid markers). The robustness of this topology is tested by examining a full plastome dataset with 140 species and a nuclear target-capture dataset with 39 species of Solanum (Angiosperms353 probe set). Key resultsWhile the taxonomic framework of Solanum remained stable, gene tree conflicts and discordance between phylogenetic trees generated from the target-capture and plastome datasets were observed. The latter correspond to regions with short internodal branches, and network analysis and polytomy tests suggest the backbone is composed of three polytomies found at different evolutionary depths. The strongest area of discordance, near the crown node of Solanum, could potentially represent a hard polytomy. ConclusionsWe argue that incomplete lineage sorting due to rapid diversification is the most likely cause for these polytomies, and that embracing the uncertainty that underlies them is crucial to understand the evolution of large and rapidly radiating lineages.

evolutionary biology↗

bioRxiv2020

Codon arrangement modulates MHC-I peptides presentation

MHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP-coding codons (MCCs), while excluding the MCC per se. CAMAP predictions were significantly more accurate when using original codon sequences than shuffled codon sequences which reflect amino acid usage. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules and applied to several cell types and species. Combining MAP ligand scores, transcript expression level and CAMAP scores was particularly useful to increaser MAP prediction accuracy. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking the MCCs (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome. Author summaryMHC-I associated peptides (MAPs) are small fragments of intracellular proteins presented at the surface of cells and used by the immune system to detect and eliminate cancerous or virus-infected cells. While it is theoretically possible to predict which portions of the intracellular proteins will be naturally processed by the cells to ultimately reach the surface, current methodologies have prohibitively high false discovery rates. Here we introduce an artificial neural network called Codon Arrangement MAP Predictor (CAMAP) which integrates information from mRNA-to-protein translation to other factors regulating MAP biogenesis (e.g. MAP ligand score and transcript expression levels) to improve MAP prediction accuracy. While most MAP predictive approaches focus on MAP sequences per se, CAMAPs novelty is to analyze the MAP-flanking mRNA sequences, thereby providing completely independent information for MAP prediction. We show on several datasets that the integration of CAMAP scores with other known factors involved in MAP presentation (i.e. MAP ligand score and mRNA expression) significantly improves MAP prediction accuracy, and further validate CAMAP learned features using an in-vitro assay. These findings may have major implications for the design of vaccines against cancers and viruses, and in times of pandemics could accelerate the identification of relevant MAPs of viral origins.

bioinformatics↗