Grant Kinsler
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grantkinsler.bsky.social
Grant Kinsler
@grantkinsler.bsky.social
Postdoc at UPenn thinking about mutations, cells, and evolution.
Pinned
Excited to share SpaceBar - our new method for labeling and detecting clones with imaging-based spatial transcriptomics platforms! w/ Yael Heyman and @arjunraj.bsky.social www.biorxiv.org/content/10.1... 🧵
Reposted by Grant Kinsler
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
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...
shorturl.at
November 12, 2025 at 8:34 PM
Reposted by Grant Kinsler
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.
November 6, 2025 at 9:51 PM
Reposted by Grant Kinsler
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...
www.biorxiv.org
November 6, 2025 at 10:03 PM
Reposted by Grant Kinsler
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...
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...
www.biorxiv.org
October 22, 2025 at 5:46 PM
Reposted by Grant Kinsler
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...
Somatic mutation and selection at population scale - Nature
A new version of nanorate DNA&nbsp;sequencing, with an&nbsp;error rate&nbsp;lower than five errors&nbsp;per billion base pairs&nbsp;and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection&nbsp;and&nbsp;the generation of high-resolution&nbsp;selection&nbsp;maps across coding and non-coding sites for many genes.
www.nature.com
October 8, 2025 at 4:31 PM
Reposted by Grant Kinsler
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
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.
rdcu.be
September 10, 2025 at 4:17 PM
Reposted by Grant Kinsler
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:
September 10, 2025 at 4:46 PM
Reposted by Grant Kinsler
How common are frequency dependent fitness effects?

New preprint out today 👇
doi.org/10.1101/2025...
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.
doi.org
August 21, 2025 at 7:23 PM
Reposted by Grant Kinsler
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.
August 6, 2025 at 5:18 PM
Reposted by Grant Kinsler
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...
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...
www.biorxiv.org
August 5, 2025 at 12:56 AM
Reposted by Grant Kinsler
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
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...
journals.plos.org
July 22, 2025 at 10:56 PM
Reposted by Grant Kinsler
New review article with @mmdesai.bsky.social is out today! Grateful for the opportunity to contribute something we hope will serve the community well
July 21, 2025 at 5:30 PM
Reposted by Grant Kinsler
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
Junior, Assistant, or Associate Specialist – Xue Lab
University of California, Irvine is hiring. Apply now!
recruit.ap.uci.edu
July 17, 2025 at 8:32 PM
Reposted by Grant Kinsler
[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...
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....
www.biorxiv.org
July 15, 2025 at 3:44 PM
Reposted by Grant Kinsler
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...
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...
www.biorxiv.org
July 15, 2025 at 3:43 PM
Reposted by Grant Kinsler
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/...
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 ...
www.science.org
June 20, 2025 at 8:25 PM
Reposted by Grant Kinsler
Delighted to share our latest on longitudinal methylation dynamics preceding cancer. Epigenetic signs of AML appear in blood DECADES before Dx.
👉 Early cancer detection
👉 Methylation drivers
👉 Epimutation rates
👉 CpG lineage tracing

www.biorxiv.org/content/10.1...
July 3, 2025 at 8:47 PM
Reposted by Grant Kinsler
Another super interesting paper from @jamieblundell.bsky.social on signatures of cancer that appear long before the clinical diagnosis. www.biorxiv.org/content/10.1...
Methylation dynamics in the decades preceding acute myeloid leukaemia
DNA methylation is emerging as a highly sensitive and specific marker of cancer initiation and progression. How these cancer-specific methylation changes are established in the decades before cancer, ...
www.biorxiv.org
July 9, 2025 at 2:29 PM
Reposted by Grant Kinsler
Excited to share our latest by my postdoc Ben KS: we use statistical physics & Bayesian inference to model genome-wide perturbation outcomes. Remarkably, perturbation responses are encoded in gene "chatter" even before the perturbation–a fundamental insight with broad implications
shorturl.at/2LHbw
July 6, 2025 at 10:11 PM
Reposted by Grant Kinsler
@harmitmalik.bsky.social and I had a lot of fun sharing our science with intrepid science spotlight reporter David Sokolov (not on blue sky)! I should hire him as my writing coach. Check out his excellent write-up describing our recent study here: www.fredhutch.org/en/news/spot....
July 2, 2025 at 4:43 AM
Reposted by Grant Kinsler
1/27 We have a new paper out! Turns out that snowflake yeast have been hiding a secret from us - they've evolved a (very!) crude circulatory system. Not with blood vessels or a heart, but through spontaneous fluid flows powered by their metabolism. 🧪🔬

www.science.org/doi/full/10....
June 24, 2025 at 4:52 PM
Reposted by Grant Kinsler
To what extent is cancer development deterministic and predictable..?

Does the germline genome affect that predictability...?

Preprint: www.biorxiv.org/content/10.1...
January 15, 2025 at 7:32 PM
Reposted by Grant Kinsler
Using barcodes 📊 to track cancer 💊 resistance evolution: is it clonal selection or plasticity? @fwhiting.bsky.social‬ knows! His new "Evolutionary Informed Resistance Assays" (EIRAs) framework infers resistance evolution dynamics from barcode diversity data. www.nature.com/articles/s41... @icr.ac.uk
Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding - Nature Communications
Understanding the dynamics of how drug resistance originates in cancer remains crucial, but it is not possible to observe them directly. Here, the authors construct a mathematical framework to infer d...
www.nature.com
June 20, 2025 at 12:49 PM
Reposted by Grant Kinsler
Check out this brand new fellowship from the Simon’s Foundation in Ecology and Evolution. Incoming grad students this year are eligible to apply. No citizenship restrictions. www.simonsfoundation.org/grant/simons...
Simons Graduate Fellowships in Ecology and Evolution
The purpose of these awards is to provide support for students entering U.S.-based Ph.D. programs with a plan to perform research in ecology and evolution. While we will consider all projects in ecolo...
www.simonsfoundation.org
June 2, 2025 at 5:16 PM
Reposted by Grant Kinsler
1/n 🧵 Excited to share our new paper! We developed a framework to reveal hidden simplicity in how organisms adapt to different environments, particularly focusing on antibiotic resistance evolution. #EvolutionaryBiology #MachineLearning
Learning the Shape of Evolutionary Landscapes: Geometric Deep Learning Reveals Hidden Structure in Phenotype-to-Fitness Maps https://www.biorxiv.org/content/10.1101/2025.05.07.652616v1
May 15, 2025 at 2:33 PM