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Updated: Sep 15, 2025

Following the Dynamics of Structural Variants in Experimentally Evolved Populations
Published on: February 3, 2023
Coalescence and Translation: A Language Model for Population Genetics
Kevin Korfmann1, Nathaniel S Pope1, Melinda Meleghy2
1University of Oregon, Institute of Ecology and Evolution, Eugene, USA.
Abstract:
Probabilistic models such as the sequentially Markovian coalescent (SMC) have long provided a powerful framework for population genetic inference, enabling reconstruction of demographic history and ancestral relationships from genomic data. However, these methods are inherently specialized, relying on predefined assumptions and/or limited scalability. Recent advances in simulation and deep learning provide an alternative approach: learning directly to generalize from synthetic genetic data to infer specific hidden evolutionary processes. Here we reframe the inference of coalescence times as a problem of translation between two biological languages: the sparse, observable patterns of mutation along the genome and the unobservable ancestral recombination graph (ARG) that gave rise to them. Inspired by large language models, we develop cxt, a decoder-only transformer that autoregressively predicts coalescent events conditioned on local mutational context. We show that cxt performs on par with state-of-the-art MCMC-based likelihood models across a broad range of demographic scenarios, including both in-distribution and out-of-distribution settings. Trained on simulations spanning the stdpopsim catalog, the model generalizes robustly and enables efficient inference at scale, producing over a million coalescence predictions in minutes. In addition cxt produces a well calibrated approximate posterior distribution of its predictions, enabling principled uncertainty quantification. Our work moves towards a foundation model for population genetics, bridging deep learning and coalescent theory to enable flexible, scalable inference of genealogical history from genomic data.
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