Fine mapping of major QTL qshgd1 for spontaneous haploid genome doubling in maize (Zea mays L.).

KEY MESSAGE: A large-effect QTL was fine mapped, which revealed 79 gene models, with 10 promising candidate genes, along with a novel inversion. In commercial maize breeding, doubled haploid (DH) technology is arguably the most efficient resource for rapidly developing novel, completely homozygous lines. However, the DH strategy, using in vivo haploid induction, currently requires the use of mutagenic agents which can be not only hazardous, but laborious. This study focuses on an alternative approach to develop DH lines-spontaneous haploid genome duplication (SHGD) via naturally restored haploid male fertility (HMF). Inbred lines A427 and Wf9, the former with high HMF and the latter with low HMF, were selected to fine-map a large-effect QTL associated with SHGD-qshgd1. SHGD alleles were derived from A427, with novel haploid recombinant groups having varying levels of the A427 chromosomal region recovered. The chromosomal region of interest is composed of 45 megabases (Mb) of genetic information on chromosome 5. Significant differences between haploid recombinant groups for HMF were identified, signaling the possibility of mapping the QTL more closely. Due to suppression of recombination from the proximity of the centromere, and a newly discovered inversion region, the associated QTL was only confined to a 25 Mb region, within which only a single recombinant was observed among ca. 9,000 BC1 individuals. Nevertheless, 79 gene models were identified within this 25 Mb region. Additionally, 10 promising candidate genes, based on RNA-seq data, are described for future evaluation, while the narrowed down genome region is accessible for straightforward introgression into elite germplasm by BC methods.

The Ga1 locus of the genus Zea is associated with novel genome structures derived from multiple, independent nonhomologous recombination events.

The Ga1 locus controls cross-incompatibility between field corn and popcorn. The Ga1-S haplotype contains 2 types of pectin methylesterase (PME) genes, ZmPme3 and several copies of ZmGa1P that are expressed in silk and pollen, respectively. The ga1 haplotype contains nonfunctional tandem repeat sequences related to ZmPme3 and ZmGa1P. This haplotype can cross-pollinate freely and is widely present in field corn. The primary objective of this study is to characterize the repeat sequences from a diverse collection of maize and teosinte lines and use this information to understand the evolution of the Ga1 locus. First, we characterized the complexity of the Ga1 genome region in high-quality maize genome assemblies that led to their categorization into 5 groups based on the number and type of PME-like sequences found at this region. Second, we studied duplication events that led to the ga1 and Ga1-S repeats using maximum likelihood phylogenetic reconstruction. Divergence estimates of the ga1 haplotype suggest that the duplication events occurred more than 600 KYA whereas those in Ga1-S occurred at 3 time points, i.e. >600, ∼260, and ∼100 KYA. These estimates suggest that the ga1 and Ga1-S tandem duplication events occurred independently. Finally, analysis of ZmPme3 and ZmGa1P homologs in Zea and Tripsacum genomes suggests that ga1 and Ga1-S repeats originated from an ancestral pair of PME genes that duplicated and diverged through 2 evolutionary branches prior to the domestication of maize.

Unraveling Prevalence and Effects of Deleterious Mutations in Maize Elite Lines across Decades of Modern Breeding.

Future breeding is likely to involve the detection and removal of deleterious alleles, which are mutations that negatively affect crop fitness. However, little is known about the prevalence of such mutations and their effects on phenotypic traits in the context of modern crop breeding. To address this, we examined the number and frequency of deleterious mutations in 350 elite maize inbred lines developed over the past few decades in China and the United States. Our findings reveal an accumulation of weakly deleterious mutations and a decrease in strongly deleterious mutations, indicating the dominant effects of genetic drift and purifying selection for the two types of mutations, respectively. We also discovered that slightly deleterious mutations, when at lower frequencies, were more likely to be heterozygous in the developed hybrids. This is consistent with complementation as a potential explanation for heterosis. Subsequently, we found that deleterious mutations accounted for more of the variation in phenotypic traits than nondeleterious mutations with matched minor allele frequencies, especially for traits related to leaf angle and flowering time. Moreover, we detected fewer deleterious mutations in the promoter and gene body regions of differentially expressed genes across breeding eras than in nondifferentially expressed genes. Overall, our results provide a comprehensive assessment of the prevalence and impact of deleterious mutations in modern maize breeding and establish a useful baseline for future maize improvement efforts.

A complete telomere-to-telomere assembly of the maize genome.

A complete telomere-to-telomere (T2T) finished genome has been the long pursuit of genomic research. Through generating deep coverage ultralong Oxford Nanopore Technology (ONT) and PacBio HiFi reads, we report here a complete genome assembly of maize with each chromosome entirely traversed in a single contig. The 2,178.6 Mb T2T Mo17 genome with a base accuracy of over 99.99% unveiled the structural features of all repetitive regions of the genome. There were several super-long simple-sequence-repeat arrays having consecutive thymine-adenine-guanine (TAG) tri-nucleotide repeats up to 235 kb. The assembly of the entire nucleolar organizer region of the 26.8 Mb array with 2,974 45S rDNA copies revealed the enormously complex patterns of rDNA duplications and transposon insertions. Additionally, complete assemblies of all ten centromeres enabled us to precisely dissect the repeat compositions of both CentC-rich and CentC-poor centromeres. The complete Mo17 genome represents a major step forward in understanding the complexity of the highly recalcitrant repetitive regions of higher plant genomes.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

A happy accident: a novel turfgrass reference genome.

Poa pratensis, commonly known as Kentucky bluegrass, is a popular cool-season grass species used as turf in lawns and recreation areas globally. Despite its substantial economic value, a reference genome had not previously been assembled due to the genome's relatively large size and biological complexity that includes apomixis, polyploidy, and interspecific hybridization. We report here a fortuitous de novo assembly and annotation of a P. pratensis genome. Instead of sequencing the genome of a C4 grass, we accidentally sampled and sequenced tissue from a weedy P. pratensis whose stolon was intertwined with that of the C4 grass. The draft assembly consists of 6.09 Gbp with an N50 scaffold length of 65.1 Mbp, and a total of 118 scaffolds, generated using PacBio long reads and Bionano optical map technology. We annotated 256K gene models and found 58% of the genome to be composed of transposable elements. To demonstrate the applicability of the reference genome, we evaluated population structure and estimated genetic diversity in P. pratensis collected from three North American prairies, two in Manitoba, Canada and one in Colorado, USA. Our results support previous studies that found high genetic diversity and population structure within the species. The reference genome and annotation will be an important resource for turfgrass breeding and study of bluegrasses.

Targeting SELPLG/P-selectin glycoprotein ligand 1 in preclinical ARDS: Genetic and epigenetic regulation of the SELPLG promoter.

We previously identified a missense single nucleotide polymorphism rs2228315 (G>A, Met62Ile) in the selectin-P-ligand gene (SELPLG), encoding P-selectin glycoprotein ligand 1 (PSGL-1), to be associated with increased susceptibility to acute respiratory distress syndrome (ARDS). These earlier studies demonstrated that SELPLG lung tissue expression was increased in mice exposed to lipopolysaccharide (LPS)- and ventilator-induced lung injury (VILI) suggesting that inflammatory and epigenetic factors regulate SELPLG promoter activity and transcription. In this report, we used a novel recombinant tandem PSGL1 immunoglobulin fusion molecule (TSGL-Ig), a competitive inhibitor of PSGL1/P-selectin interactions, to demonstrate significant TSGL-Ig-mediated decreases in SELPLG lung tissue expression as well as highly significant protection from LPS- and VILI-induced lung injury. In vitro studies examined the effects of key ARDS stimuli (LPS, 18% cyclic stretch to simulate VILI) on SELPLG promoter activity and showed LPS-mediated increases in SELPLG promoter activity and identified putative promoter regions associated with increased SELPLG expression. SELPLG promoter activity was strongly regulated by the key hypoxia-inducible transcription factors, HIF-1α, and HIF-2α as well as NRF2. Finally, the transcriptional regulation of SELPLG promoter by ARDS stimuli and the effect of DNA methylation on SELPLG expression in endothelial cell was confirmed. These findings indicate SELPLG transcriptional regulation by clinically-relevant inflammatory factors with the significant TSGL-Ig-mediated attenuation of LPS and VILI highly consistent with PSGL1/P-selectin as therapeutic targets in ARDS.

ERG Functionally Overlaps with Other Ets Proteins in Promoting TH9 Cell Expression of Il9 during Allergic Lung Inflammation.

CD4+ TH cells develop into subsets that are specialized in the secretion of particular cytokines to mediate restricted types of inflammation and immune responses. Among the subsets that promote development of allergic inflammatory responses, IL-9-producing TH9 cells are regulated by a number of transcription factors. We have previously shown that the E26 transformation-specific (Ets) family members PU.1 and Ets translocation variant 5 (ETV5) function in parallel to regulate IL-9. In this study we identified a third member of the Ets family of transcription factors, Ets-related gene (ERG), that mediates IL-9 production in TH9 cells in the absence of PU.1 and ETV5. Chromatin immunoprecipitation assays revealed that ERG interaction at the Il9 promoter region is restricted to the TH9 lineage and is sustained during murine TH9 polarization. Knockdown or knockout of ERG during murine or human TH9 polarization in vitro led to a decrease in IL-9 production in TH9 cells. Deletion of ERG in vivo had modest effects on IL-9 production in vitro or in vivo. However, in the absence of PU.1 and ETV5, ERG was required for residual IL-9 production in vitro and for IL-9 production by lung-derived CD4 T cells in a mouse model of chronic allergic airway disease. Thus, ERG contributes to IL-9 regulation in TH9 cells.

Allele-specific Expression Reveals Multiple Paths to Highland Adaptation in Maize.

Maize is a staple food of smallholder farmers living in highland regions up to 4,000 m above sea level worldwide. Mexican and South American highlands are two major highland maize growing regions, and population genetic data suggest the maize's adaptation to these regions occurred largely independently, providing a case study for convergent evolution. To better understand the mechanistic basis of highland adaptation, we crossed maize landraces from 108 highland and lowland sites of Mexico and South America with the inbred line B73 to produce F1 hybrids and grew them in both highland and lowland sites in Mexico. We identified thousands of genes with divergent expression between highland and lowland populations. Hundreds of these genes show patterns of convergent evolution between Mexico and South America. To dissect the genetic architecture of the divergent gene expression, we developed a novel allele-specific expression analysis pipeline to detect genes with divergent functional cis-regulatory variation between highland and lowland populations. We identified hundreds of genes with divergent cis-regulation between highland and lowland landrace alleles, with 20 in common between regions, further suggesting convergence in the genes underlying highland adaptation. Further analyses suggest multiple mechanisms contribute to this convergence in gene regulation. Although the vast majority of evolutionary changes associated with highland adaptation were region specific, our findings highlight an important role for convergence at the gene expression and gene regulation levels as well.

Biochemical and genomic identification of novel biomarkers in progressive sarcoidosis: HBEGF, eNAMPT, and ANG-2.

Background: Progressive pulmonary fibrosis is a serious complication in subjects with sarcoidosis. The absence of reliable, non-invasive biomarkers that detect early progression exacerbates the difficulty in predicting sarcoidosis severity. To potentially address this unmet need, we evaluated a panel of markers for an association with sarcoidosis progression (HBEGF, NAMPT, IL1-RA, IL-6, IL-8, ANG-2). This panel encompasses proteins related to inflammation, vascular injury, cell proliferation, and fibroblast mitogenesis processes. Methods: Plasma biomarker levels and biomarker protein expression in lung and lymph nodes tissues (immunohistochemical studies) from sarcoidosis subjects with limited disease and progressive (complicated) sarcoidosis were performed. Gene expression of the protein-coding genes included in this panel was analyzed using RNAseq in sarcoidosis granulomatous tissues from lung and lymph nodes. Results: Except for IL-8, plasma levels of each biomarker-eNAMPT, IL-1RA, IL-6, ANG-2, and HBEGF-were significantly elevated in sarcoidosis subjects compared to controls. In addition, plasma levels of HBEGF were elevated in complicated sarcoidosis, while eNAMPT and ANG-2 were observed to serve as markers of lung fibrosis in a subgroup of complicated sarcoidosis. Genomic studies corroborated HBEGF and NAMPT among the top dysregulated genes and identified cytokine-related and fibrotic pathways in lung granulomatous tissues from sarcoidosis. Conclusion: These findings suggest HBEGF, eNAMPT, and ANG-2 may serve as potential novel indicators of the clinical severity of sarcoidosis disease.

Genome sequencing reveals evidence of adaptive variation in the genus Zea.

Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in wild relatives of maize. Here, we characterize a high-density genomic variation map from 744 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 70 million single-nucleotide polymorphisms. The variation map reveals evidence of selection within taxa displaying novel adaptations. We focus on adaptive alleles in highland teosinte and temperate maize, highlighting the key role of flowering-time-related pathways in their adaptation. To show the utility of variants in these data, we generate mutant alleles for two flowering-time candidate genes. This work provides an extensive sampling of the genetic diversity of Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.

eNAMPT Neutralization Preserves Lung Fluid Balance and Reduces Acute Renal Injury in Porcine Sepsis/VILI-Induced Inflammatory Lung Injury.

Background: Numerous potential ARDS therapeutics, based upon preclinical successful rodent studies that utilized LPS challenge without mechanical ventilation, have failed in Phase 2/3 clinical trials. Recently, ALT-100 mAb, a novel biologic that neutralizes the TLR4 ligand and DAMP, eNAMPT (extracellular nicotinamide phosphoribosyltransferase), was shown to reduce septic shock/VILI-induced porcine lung injury when delivered 2 h after injury onset. We now examine the ALT-100 mAb efficacy on acute kidney injury (AKI) and lung fluid balance in a porcine ARDS/VILI model when delivered 6 h post injury. Methods/Results: Compared to control PBS-treated pigs, exposure of ALT-100 mAb-treated pigs (0.4 mg/kg, 2 h or 6 h after injury initiation) to LPS-induced pneumonia/septic shock and VILI (12 h), demonstrated significantly diminished lung injury severity (histology, BAL PMNs, plasma cytokines), biochemical/genomic evidence of NF-kB/MAP kinase/cytokine receptor signaling, and AKI (histology, plasma lipocalin). ALT-100 mAb treatment effectively preserved lung fluid balance reflected by reduced BAL protein/tissue albumin levels, lung wet/dry tissue ratios, ultrasound-derived B lines, and chest radiograph opacities. Delayed ALT-100 mAb at 2 h was significantly more protective than 6 h delivery only for plasma eNAMPT while trending toward greater protection for remaining inflammatory indices. Delayed ALT-100 treatment also decreased lung/renal injury indices in LPS/VILI-exposed rats when delivered up to 12 h after LPS. Conclusions: These studies indicate the delayed delivery of the eNAMPT-neutralizing ALT-100 mAb reduces inflammatory lung injury, preserves lung fluid balance, and reduces multi-organ dysfunction, and may potentially address the unmet need for novel therapeutics that reduce ARDS/VILI mortality.

Convergent domestication: Finding the genes that make crops.

A recent study shows that convergent selection of orthologs encoding a WD40 protein in maize and rice occurs during domestication. Knockout of these genes increases yield in both crops with no detectable effects on other agronomic traits. Identification of convergent selection can focus improvement efforts.

An adaptive teosinte mexicana introgression modulates phosphatidylcholine levels and is associated with maize flowering time.

Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.

Demonstration of local adaptation in maize landraces by reciprocal transplantation.

Populations are locally adapted when they exhibit higher fitness than foreign populations in their native habitat. Maize landrace adaptations to highland and lowland conditions are of interest to researchers and breeders. To determine the prevalence and strength of local adaptation in maize landraces, we performed a reciprocal transplant experiment across an elevational gradient in Mexico. We grew 120 landraces, grouped into four populations (Mexican Highland, Mexican Lowland, South American Highland, South American Lowland), in Mexican highland and lowland common gardens and collected phenotypes relevant to fitness and known highland-adaptive traits such as anthocyanin pigmentation and macrohair density. 67k DArTseq markers were generated from field specimens to allow comparisons between phenotypic patterns and population genetic structure. We found phenotypic patterns consistent with local adaptation, though these patterns differ between the Mexican and South American populations. Quantitative trait differentiation (Q ST) was greater than neutral allele frequency differentiation (F ST) for many traits, signaling directional selection between pairs of populations. All populations exhibited higher fitness metric values when grown at their native elevation, and Mexican landraces had higher fitness than South American landraces when grown in these Mexican sites. As environmental distance between landraces' native collection sites and common garden sites increased, fitness values dropped, suggesting landraces are adapted to environmental conditions at their natal sites. Correlations between fitness and anthocyanin pigmentation and macrohair traits were stronger in the highland site than the lowland site, supporting their status as highland-adaptive. These results give substance to the long-held presumption of local adaptation of New World maize landraces to elevation and other environmental variables across North and South America.

Critical role for the lung endothelial nonmuscle myosin light-chain kinase isoform in the severity of inflammatory murine lung injury.

Global knockout of the nonmuscle isoform of myosin light-chain kinase (nmMLCK), a primary cellular regulator of cytoskeletal machinery, is strongly protective in preclinical murine models of inflammatory lung injury. The current study was designed to assess the specific contribution of endothelial cell (EC) nmMLCK to the severity of murine inflammatory lung injury produced by lipopolysaccharide (LPS) and mechanical ventilation ventilator-induced lung injury or ventilation (VILI). Responses to combined LPS/VILI exposure were assessed in: (i) wild-type (WT) C57BL/6J mice; (ii) transgenic mice with global deletion of nmMLCK (nmMylk -/-); (iii) transgenic nmMylk -/- mice with overexpression of nmMLCK restricted to the endothelium (nmMylk -/-/ec-tg+). Lung inflammation indices included lung histology, bronchoalveolar lavage (BAL) polymorphonuclear leukocytes (PMNs), lung protein biochemistry, tissue albumin levels, Evans blue dye (EBD) lung extravasation, and plasma cytokines (interleukin-6 [IL-6], keratinocyte chemoattractant [KC]/IL-8, IL-1bß, extracellular nicotinamide phosphoribosyltransferase, tumor necrosis factor-α). Compared to WT C57BL/6J mice, the severity of LPS/VILI-induced lung injury was markedly reduced in mice with global nmMLCK deletion reflected by reductions in histologic inflammatory lung injury, BAL PMN counts, mitogen-activated protein kinase, and NF-kB pathway activation in lung homogenates, plasma cytokine levels, and parameters of lung permeability (increased BAL protein, tissue albumin levels, EBD lung extravasation). In contrast, mice with restricted overexpression of nmMLCK in EC (nmMylk -/-/ec-tg+) showed significant persistence of LPS/VILI-induced lung injury severity compared to WT mice. In conclusion, these studies strongly endorse the role of EC nmMLCK in driving the severity of preclinical inflammatory lung injury. Precise targeting of EC nmMLCK may represent an attractive therapeutic strategy to reduce lung inflammation and both lung and systemic vascular permeability.

Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial.

Background: In the phase 2/3 BLAZE-1 trial, bamlanivimab and etesevimab together reduced coronavirus disease 2019 (COVID-19)-related hospitalizations and any-cause mortality in ambulatory patients. Herein, we assess the impact of bamlanivimab and etesevimab treatment on the severity and length of symptoms and health outcomes among patients at increased risk for severe COVID-19. Methods: In the phase 3 portion of BLAZE-1 (NCT04427501), symptomatic patients with increased risk for severe COVID-19 were randomized (2:1) to a single infusion of 700 mg bamlanivimab and 1400 mg etesevimab or placebo. Hospitalization events, vital signs, and symptomatology were monitored throughout the trial. Results: Overall, 769 patients were randomized to bamlanivimab and etesevimab together (n = 511) or placebo (n = 258). The time to sustained symptom resolution was significantly shorter among patients who received bamlanivimab and etesevimab compared with placebo (8 vs 10 days; P < .01). The median time to first sustained symptom resolution of body aches and pain, chills, fatigue, feeling feverish, headache, and shortness of breath was significantly different in patients receiving bamlanivimab and etesevimab compared to placebo (P < .05). The proportion of patients who experienced COVID-19-related hospitalization by day 29 was significantly reduced among the bamlanivimab and etesevimab group compared with placebo (0.8% vs 5.4%; P < .01). The mean duration of hospital stay was numerically shorter among patients who received bamlanivimab and etesevimab (7.3 vs 13.5 days; P = .16), with fewer intensive care admissions. Conclusions: Patients receiving bamlanivimab and etesevimab together resolved their symptoms more rapidly than those receiving placebo. Bamlanivimab and etesevimab treatment was associated with reduced rates of hospitalizations and shorter hospital stays. Clinical Trials Registration: NCT04427501.

A B73×Palomero Toluqueño mapping population reveals local adaptation in Mexican highland maize.

Generations of farmer selection in the central Mexican highlands have produced unique maize varieties adapted to the challenges of the local environment. In addition to possessing great agronomic and cultural value, Mexican highland maize represents a good system for the study of local adaptation and acquisition of adaptive phenotypes under cultivation. In this study, we characterize a recombinant inbred line population derived from the B73 reference line and the Mexican highland maize variety Palomero Toluqueño. B73 and Palomero Toluqueño showed classic rank-changing differences in performance between lowland and highland field sites, indicative of local adaptation. Quantitative trait mapping identified genomic regions linked to effects on yield components that were conditionally expressed depending on the environment. For the principal genomic regions associated with ear weight and total kernel number, the Palomero Toluqueño allele conferred an advantage specifically in the highland site, consistent with local adaptation. We identified Palomero Toluqueño alleles associated with expression of characteristic highland traits, including reduced tassel branching, increased sheath pigmentation and the presence of sheath macrohairs. The oligogenic architecture of these three morphological traits supports their role in adaptation, suggesting they have arisen from consistent directional selection acting at distinct points across the genome. We discuss these results in the context of the origin of phenotypic novelty during selection, commenting on the role of de novo mutation and the acquisition of adaptive variation by gene flow from endemic wild relatives.