Research

Mutations are the ultimate source of all genetic variation, yet mutation rates vary orders of magnitude across the genome, among cell types, and across species. We use ultra-accurate sequencing technologies — including Duplex Sequencing — to characterize mutation rates and spectra at unprecedented resolution. A central question is why mutation rates are systematically lower in functionally important regions of the genome, and what molecular mechanisms underlie this pattern.

Current projects include:

• Epigenome-recruited DNA repair and mutation rate reduction in plants

• Somatic mutation dynamics and deleterious variation in clonal walnut and pistachio cultivars

• Mutation bias and natural selection in Arabidopsis thaliana

• Mechanisms of mutation rate variation across the plant kingdom

A key discovery from the lab is that the histone mark H3K4me1 directly recruits DNA repair proteins in plants, providing a mechanistic explanation for why mutation rates are lower in gene-rich, H3K4me-enriched regions of the genome. We are extending this work to understand how chromatin-targeted DNA repair has evolved independently across the tree of life and how these mechanisms shape the landscape of genetic variation within and among species.

Current projects include:

• H3K4me-associated hypomutation in plants

• Convergent evolution of epigenome-recruited DNA repair across the tree of life

• Chromatin features predicting intron architecture and mutation rates

Plants harbor extraordinary structural variation — inversions, transposable elements, copy number variants, and pan-genome loci present in some individuals but absent in others. We use long-read sequencing and comparative genomics to characterize this variation and understand how it contributes to phenotypic diversity, reproductive biology, and local adaptation across plant populations and species.

Current projects include:

• Pistachio pan-genome and multi-genome reference

• Comparative genomics of repeat-rich and structurally complex plant genomes

• Segregation distortion and unusual chromosome biology in alfalfa and other polyploids

We leverage natural loss-of-function alleles to infer gene function at population scale — an approach we call functional GWAS or loss-of-function burden testing. By identifying which genes, when disrupted, produce detectable phenotypic effects across individuals, we can discover gene functions systematically and without prior functional annotation. This scales to any species with population-level genomic data and provides direct targets for breeding, gene editing, and understanding evolution.

This work builds on our foundational studies of adaptive loss-of-function in plants and extends them into crop systems where understanding which genes matter — and how — has direct practical value.

Current projects include:

• Loss-of-function burden testing in cassava (Manihot esculenta) landraces

• Loss-of-function variation in diploid wheat (Triticum monococcum)

• Scalable frameworks for functional gene discovery across crop species

Many of the world’s crop species remain genomically understudied. We build genomic resources — reference genomes, pan-genomes, population-scale sequencing datasets — for these species and use them to study the genetic basis of agriculturally important traits, climate adaptation, and fundamental questions about genome evolution.

Species we have worked with include pistachio (Pistacia vera), walnut (Juglans regia), cassava (Manihot esculenta), celery (Apium graveolens), diploid wheat (Triticum monococcum), rice (Oryza sativa), alfalfa (Medicago sativa), almonds (Prunus dulcis), and black cottonwood (Populus trichocarpa). Projects range from understanding mutation histories of clonal cultivars to assembling reference genomes for breeding and fundamental science.

Current projects include:

• Pistachio pan-genome, reference genome, and kernel development

• Cassava population genomics and climate adaptation in Colombian landraces

• Climate adaptation and somatic mutation in Populus trichocarpa

• Genome assembly and annotation for celery, wheat, and other crop species