Biology subjects

Healey, A. L.

Publications and source records attributed to Healey, A. L..

5 recordsLinked to original sources

bioRxiv2026

Pangenomics and machine learning reveal genetic variation to optimize carotenoids in sorghum grain

Enhancing grain carotenoid concentration to increase yellowness and provitamin A content in sorghum (Sorghum bicolor [L.] Moench) is a major breeding objective across sub-Saharan Africa. Carotenoid breeding is constrained by costly post-harvest phenotyping and can be accelerated through genetic markers that capture functional variation in key carotenoid biosynthesis genes. Zeaxanthin epoxidase (ZEP) is a major gene controlling sorghum grain carotenoid accumulation, and SNP-based KASP markers facilitate selection of high-carotenoid grain, although quantitative variation remains among lines carrying the favorable allele. We hypothesized that additional functional variation within ZEP and other carotenoid biosynthesis pathway genes contributes to this variation and can be revealed by a pangenome-informed analysis. Using a 33-member pangenome reference, we characterized sequence and structural variation at ZEP and other key carotenoid biosynthesis genes and applied pangenome-derived genotyping to study marker diversity associated with carotenoid accumulation. Evaluation of ZEP in the pangenome reference revealed previously uncharacterized structural variation that is absent from the BTx623 primary reference genome. A pangenome-based association analysis identified genetic markers associated with the accumulation of carotenoids which were specific to particular pangenome reference members, including in RTx430 and SRN39, both yellow endosperm lines. Machine learning identified markers in ZEP, {beta}-OH, ZDS, and Z-ISO as the most predictive for all carotenoid traits, suggesting a multi-locus genetic architecture underlies the accumulation of carotenoids in sorghum grain. By integrating sorghum pangenomic resources with machine learning, this study establishes a framework for pangenome-accelerated trait discovery and identifies new genetic targets for carotenoid biofortification in sorghum.

genomics↗

bioRxiv2025

Delivering trait-enhanced varieties to African smallholders through a pangenomic breeding network

Pangenomics has been promoted to accelerate breeding of orphan crops, but smallholder farmers in developing nations have seen little benefit so far. To address this gap, we built a global pangenomic breeding network, integrating African breeding programs, U.S. land grant universities, and international nonprofit research organizations. Here we demonstrate that pangenomics, when integrated with local crop improvement knowledge and global scientific partnerships, can facilitate breeding of drought and pest resilient varieties for smallholders. To breed trait-enhanced sorghum varieties with lgs1-1 resistance to witchweed (Striga hermonthica) for smallholders in Niger, one of the worlds least developed nations, we used population genomics across local and global scales to develop lgs1-1 Striga resistance markers, and deployed them for rapid introgression of resistance into locally-preferred varieties. Genomic characterization, along with controlled experiments in laboratory, pot, field stations, and smallholder farms, confirmed lgs1-1 resistance was introgressed without loss of essential local-preference traits. New pangenomic resources, including global resequencing and graph pangenomes, further accelerated design of broadly-applicable markers. Unlocking the potential of pangenomics for stress-resilience breeding depended on stakeholder input, strong inference, South-led decision support software, and a dense collaborative network. The experience of the network provides a scalable roadmap for collaborative pangenomic breeding of trait-enhanced varieties for the worlds lowest-resourced farmers.

genomics↗

bioRxiv2025

Developing future resilience from signatures of adaptation across the sorghum pangenome

While the green revolution adapted a handful of crops to homogenous and high-input industrialized agriculture, much of the global population still relies on local food production from low-input smallholder farms that grow highly variable crop cultivars. The high diversity of the grain and bioenergy crop sorghum 1-4, and many other crops that were not homogenized during the green revolution 5, not only provides the raw materials for breeders to make substantial gains in cultivar improvement, but also constrains breeding efforts due to highly specialized locally adapted plant phenotypes 6. Here, we construct a 33-member pangenome and identify trait-associated variants in 1,988 cultivars and landraces. We then apply these resources to explore the complex interplay between historical contingency, ongoing adaptation, and the potential for future gains through climate-aware genome-enabled breeding. Specifically, our analyses conclusively demonstrate that multiple nested, deeply diverged, and previously uncharacterized structural variants in the domestication gene SHATTERING1 distinguish the previously established multicentric origin of sorghum. We then apply landscape genomics tests to reveal how gene flow, adaptation, and secondary contact created the complex genetic mosaic in current global breeding networks. Further analysis of climate-gene associations highlights candidate loci underlying adaptation, including the biosynthetic gene cluster for the cyanogenic glucoside dhurrin. Combined, the pangenome-informed variants developed here will enable both trait discovery and subsequent marker assays to accelerate breeding and provide a framework for similar applications in other diverse and non-model crops.

genomics↗

bioRxiv2025

Ancient pangenomic origins of noncanonical NLR genes underlying the recent evolutionary rescue of a staple crop

Evolutionary rescue occurs when populations in deteriorating environments avoid extinction by rapid adaptation. The recent evolutionary rescue of the cereal crop sorghum via RMES1 aphid resistance is among a few known in situ cases, but its pangenomic origins and molecular basis is not yet known. Here, we describe the behavioral effects, molecular endophenotypes, and pangenomic evolution underlying this evolutionary rescue. Analysis of near-isogenic lines show that RMES1 disrupts phloem feeding via global immunity activation of conserved defense networks. A growth-to-defense transition is evidenced by extensive transcriptome remodeling (>15% of expressed genes) and mediated by salicylic acid signaling. Nucleotide-binding leucine-rich repeat (NLR) immune receptor genes at the RMES1 locus harbored on a large tandem duplication have extensive copy number variation across the sorghum pangenome. The likely causative NLRs (RMES1A and RMES1B) were inferred from expression and structural variation. The NLRs encoded at RMES1 lack an N-terminal signaling domain and have nucleotide-binding domain sequence variation expected to result in a loss of ATP binding, suggesting RMES1 NLRs function via a noncanonical mechanism. The RMES1 NLR family is shared across the grass super-pangenome and includes the brown planthopper resistance gene BPH40 in Oryza sativa, which is syntenic to RMES1. Finally, k-mer analysis of RMES1 haplotypes in the sorghum pangenome established the East African origin of rare standing variation for resistance. Thus, the birth-and-death process at an ancient gene cluster generated pangenomic variation that was recruited to activate coordinated defense pathways and provide evolutionary rescue.

genetics↗

bioRxiv2024

ZW sex chromosome structure in Amborella trichopoda

Sex chromosomes have evolved hundreds of times, and their recent origins in flowering plants can shed light on the early consequences of suppressed recombination. Amborella trichopoda, the sole species on a lineage that is sister to all other extant flowering plants, is dioecious with a young ZW sex determination system. Here we present a haplotype-resolved genome assembly, including highly-contiguous assemblies of the Z and W chromosomes. We identify a [~]3-Megabase sex-determination region (SDR) captured in two strata that includes a [~]300-Kilobase inversion that is enriched with repetitive sequence and contains a homolog of the Arabidopsis METHYLTHIOADENOSINE NUCLEOSIDASE (MTN1-2) genes, which are known to be involved in fertility. However, the remainder of the SDR does not show patterns typically found in non-recombining SDRs, like repeat accumulation and gene loss. These findings are consistent with the hypothesis that dioecy is recently derived in Amborella and the sex chromosome pair has not significantly degenerated.

genomics↗