Genotype-fitness mapping of adaptive mutants reveals shifting low-dimensional structure across divergent environments Predicting the effect of a genetic mutation on fitness is a major challenge in evolutionary biology. This study uses fitness effects of a large collection of adaptive yeast mutants in multiple lab env...

Really excited that this major work from my PhD is finally published in @plosbiology.org ! In it, we were trying to tackle a fundamental question in evolution - how do genetic mutations map onto evolutionary fitness? (1/n)
journals.plos.org/plosbiology/...

Nice to see this published at @PLoS Comp Bio. Big improvements after peer review and important input from @gsherloc.bsky.social! Hopefully, this tool will be helpful for those interested in using barcodes for detecting new beneficial mutations.

journals.plos.org/ploscompbiol...

Gotta love a peppered moth story (and a soft selective sweep to boot)!

In new work by @jahn0.bsky.social and I in @jbloomlab.bsky.social, we investigate how sequence constraints differ across influenza HA subtypes.

We find ~50% of sites in HA display substantially different amino-acid preferences across H3, H5, and H7.

doi.org/10.64898/202...

SpaceBar enables single-cell-resolution clone tracing with imaging-based spatial transcriptomics - Nature Methods SpaceBar is a cellular barcoding strategy for simultaneous analysis of cell clonal and spatial identities.

SpaceBar: a cellular barcoding approach for simultaneous analysis of cell clonal and spatial identities.

www.nature.com/articles/s41...

We designed SpaceBar to be as easy to use as possible:

Cells are labeled via lentivirus transduction, and barcode detection works with any standard imaging-based spatial transcriptomics workflow.

w/ Yael Heyman and @arjunraj.bsky.social

Check out the thread from the preprint for more info!

SpaceBar enables single-cell-resolution clone tracing with imaging-based spatial transcriptomics Nature Methods - SpaceBar is a cellular barcoding strategy for simultaneous analysis of cell clonal and spatial identities.

Excited that SpaceBar is now out in Nature Methods!🥳

We combined clone tracing with spatial transcriptomics to untangle what drives gene expression in tumors: a cell's identity or its neighborhood?

Most genes were driven by location, but some showed strong clonal patterns.

rdcu.be/eVhpc

🗞️ New preprint from the lab, led by our postdoc Ana Garoña (not on here) in collab with @andreagiometto.bsky.social: “Experimental evolution of cellular miniaturization reveals a mechanism for cell size evolution”, aka: “honey, we shrank the yeasts!” 🎥
www.biorxiv.org/content/10.6...

So excited to share this work led by @alexrob.bsky.social with Ben Kerr!

We investigated a poliovirus capsid inhibitor that exploits a breakdown in the genotype-phenotype map to prevent drug resistance evolution. Or does it?

See Alex's thread, but a few extras:

#socialviruses #evosky #virosky 🧪

High-resolution mapping of a rapidly evolving complex trait reveals genotype-phenotype stability and an unpredictable genetic architecture of adaptation The extent to which adaptation can be predicted, particularly for traits with complex genetic bases, is unknown. Here, we leveraged a model complex trait, model species, and high-powered longitudinal ...

Thrilled to finally share the magnum opus of my PhD that focuses on the genetic basis of evolutionary change! Specifically, we know we can map the genetic basis of a trait, but can we tell which genes will underlie the trait shift when it evolves? doi.org/10.1101/2025...

Insertion of an invading retrovirus regulates a novel color trait in swordtail fish For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable wi...

I am so excited to share new work on a TE insertion that regulates iridescence in swordtails, led by fantastic grad student @nadiahaghani.bsky.social and with help from many coauthors! In a time that has been so difficult to navigate, this & other projects have kept my spirits up: shorturl.at/NE65A

Glass beads of all sorts balancing on wavy threads.

How is functional variation at large-effect loci maintained in natural populations, even as environments change? In a paper led by @mkarag.bsky.social, we tracked known pesticide resistant alleles in outdoor 𝘋. 𝘮𝘦𝘭𝘢𝘯𝘰𝘨𝘢𝘴𝘵𝘦𝘳 cages & inferred selection and dominance from temporal sequencing data.

Excited to share our recent work from @lowelab.bsky.social on the intersection of life history and cell type evolution: www.biorxiv.org/content/10.1...

Massively parallel interrogation of the fitness of natural variants in ancient signaling pathways reveals pervasive local adaptation The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are almost always neutral as suggested by neutral and n...

One of the most exciting works of my career, years in the making. We used high-throughput precision genome editing to test the fitness effects of thousands of natural variants. Our findings challenge the long-held assumption that common variants are inconsequential.

www.biorxiv.org/content/10.1...

Somatic mutation and selection at population scale - Nature A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Our latest work is out in Nature today. In this paper, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people www.nature.com/articles/s41...

Fluctuating DNA methylation tracks cancer evolution at clinical scale Nature - Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

Cancer is an evolutionary disease, but does knowing a cancer’s evolutionary past help predict its future? Out today in @nature, we learnt the evolution of 2000 lymphoid cancers and found it was highly correlated with clinical outcomes! (1/7)
rdcu.be/eFrrc

The constant barrage of terrible news on bluesky has made me feel weird about promoting papers, but people in the lab have been doing so much amazing work over the past few months that I want to share a few brief teasers/links:

Super cool work, Joao! This matches some hints we had in some of our work that this likely happens after just 1 or 2 adaptive steps in our yeast system! Glad to see it studied in detail!

Frequency-dependent fitness effects are ubiquitous In simple microbial populations, the fitness effects of most selected mutations are generally taken to be constant, independent of genotype frequency. This assumption underpins predictions about evolutionary dynamics, epistatic interactions, and the maintenance of genetic diversity in populations. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli Long-Term Evolution Experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in approximately 80\% of strain pairs tested. Most competitions exhibit negative frequency-dependence, where fitness advantages decline as mutant frequency increases. Furthermore, we demonstrate that the strength of frequency-dependence is predictable from invasion fitness measurements, with invasion fitness explaining approximately half of the biological variation in frequency-dependent slopes. Additionally, we observe violations of fitness transitivity in several strain combinations, indicating that competitive relationships cannot always be predicted from fitness relative to a single reference strain alone. Through high-resolution measurements of within-growth cycle dynamics, we show that simple resource competition explains a substantial portion of the frequency-dependence: when faster-growing genotypes dominate populations, they deplete shared resources more rapidly, reducing the time available for fitness differences to accumulate. Our results demonstrate that even in a simple model system designed to minimize ecological complexity, subtle ecological interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary dynamics. ### Competing Interest Statement The authors have declared no competing interest.

How common are frequency dependent fitness effects?

New preprint out today 👇
doi.org/10.1101/2025...

Congratulations, Roshni! Excited to see all the great things from your lab!

Bittersweet to be leaving @docedge.bsky.social after a wonderful postdoc, but excited to share that I'm joining @uoregon.bsky.social next month as an Assistant Professor in the Department of Data Science.

Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium Cells require highly polymorphic receptors to perform accurate self/non-self recognition. In the amoeba Dicytostelium discoideum, polymorphic TgrB1 & TgrC1 proteins are used to bind sister cells and e...

I'm excited to announce our new biorxiv preprint, wherein we investigate the evolution of the weirdest genetic locus I've ever seen! Behold the tgr genes of the social amoeba, which mediate self/non-self discrimination during facultative multicellularity 🐅 🧵 1/
www.biorxiv.org/content/10.1...

A high-resolution two-step evolution experiment in yeast reveals a shift from pleiotropic to modular adaptation Evolution is expected to involve mutations that are small and modular in effect, but recent findings suggest that mutations early in an adaptive process can have strong and pleiotropic effects. This s...

Having a great time at #smbe2025! So many great talks and conversations. Thank you again to @iamphioxus.bsky.social for the opportunity to present our work! Much of it is from the paper by @grantkinsler.bsky.social and @yuping-li.bsky.social journals.plos.org/plosbiology/... 1/n

Excited to read it!

New review article with @mmdesai.bsky.social is out today! Grateful for the opportunity to contribute something we hope will serve the community well

Junior, Assistant, or Associate Specialist – Xue Lab University of California, Irvine is hiring. Apply now!

The Xue lab at UC Irvine is looking for a staff scientist to support our work investigating how microbes interact and evolve in the gut microbiome! Open to a wide range of previous experience levels, see ad for more.
recruit.ap.uci.edu/JPF09601

Gastruloid patterning reflects division of labor among biased stem cell clones Embryonic development typically requires precise coordination among cells to achieve reproducible outcomes, leading to the assumption that cellular heterogeneity must be minimized or buffered against....

[0/8] Stoked to share our work with @arjunraj.bsky.social on tissue organization in the gastruloid. We use lineage tracing and spatial transcriptomics to show that diversity among stem cell clones promotes, rather than hinders, gastruloid development: www.biorxiv.org/content/10.1...

Single-cell spatial mapping reveals reproducible cell type organization and spatially-dependent gene expression in gastruloids Gastruloids are three-dimensional stem-cell-based models that recapitulate key aspects of mammalian gastrulation, including formation of an anterior-posterior (AP) axis. However, we do not have detail...

Very excited to share our new work on gastruloids by the incredible Cat Triandafillou! We mapped gene expression across 26 individual gastruloids at single-cell resolution and discovered some pretty amazing patterns about how these "mini-embryos" organize themselves.
www.biorxiv.org/content/10.1...

Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae The constraints that govern the evolution of gene expression patterns across development remain unclear. Single-cell RNA sequencing can detail these constraints by systematically profiling homologous ...

Happy to announce our paper comparing embryonic gene expression between C. elegans and C. briggsae, work led by Christopher Large with Rupa Khanal and in collaboration with Junhyong Kim and Bob Waterston. www.science.org/doi/10.1126/...

Team Avenir forever!