Genetic background sets the trajectory of experimental cancer evolution - Nature

Experimentally replaying tumour evolution in divergent mouse strains reveals the importance of interactions between genetic ancestry and acquired cancer-driving mutations in shaping the earliest stage...

nature.com

2026 Function of Evolving Systems Conference GRC

The 2026 Gordon Research Conference on Function of Evolving Systems will be held in Waterville Valley, New Hampshire. Apply today to reserve your spot.

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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...

journals.plos.org

Putting BASIL in a BLT: A Bayesian filtering method for estimating the fitness effects of nascent adaptive mutations

Author summary Beneficial mutations are rare but they are the ultimate drivers of evolution by natural selection. Evolutionary biologists seek to understand how many beneficial mutations an organism h...

journals.plos.org

Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures

Hemagglutinins (HA) from different influenza A virus subtypes share as little as ∼40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ∼50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge. ### Competing Interest Statement JDB consults for Apriori Bio, Invivyd, Pfizer, GSK, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to the deep mutational scanning of viral proteins. National Institute of Allergy and Infectious Diseases, R01AI165821, 75N93021C00015 U.S. National Science Foundation, DGE-2140004 Howard Hughes Medical Institute, https://ror.org/006w34k90

doi.org

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.

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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.

rdcu.be

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 ...

doi.org

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...

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biorxiv.org

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...

biorxiv.org

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.

nature.com

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.

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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

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...

biorxiv.org

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...

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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....

biorxiv.org

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...

biorxiv.org

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 ...

science.org

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, ...

biorxiv.org