Search arXivSearch

arXiv · 1811.03177

How Many Subpopulations is Too Many? Exponential Lower Bounds for Inferring Population Histories

Abstract

Reconstruction of population histories is a central problem in population genetics. Existing coalescent-based methods, like the seminal work of Li and Durbin (Nature, 2011), attempt to solve this problem using sequence data but have no rigorous guarantees. Determining the amount of data needed to correctly reconstruct population histories is a major challenge. Using a variety of tools from information theory, the theory of extremal polynomials, and approximation theory, we prove new sharp information-theoretic lower bounds on the problem of reconstructing population structure -- the history of multiple subpopulations that merge, split and change sizes over time. Our lower bounds are exponential in the number of subpopulations, even when reconstructing recent histories. We demonstrate the sharpness of our lower bounds by providing algorithms for distinguishing and learning population histories with matching dependence on the number of subpopulations. Along the way and of independent interest, we essentially determine the optimal number of samples needed to learn an exponential mixture distribution information-theoretically, proving the upper bound by analyzing natural (and efficient) algorithms for this problem.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Younhun Kim, Frederic Koehler, Ankur Moitra, Elchanan Mossel, Govind Ramnarayan. 2019-05-08. How Many Subpopulations is Too Many? Exponential Lower Bounds for Inferring Population Histories. https://arxiv.org/abs/1811.03177

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

A conceptual predator-prey model with super-long transients

Drawing on the understanding of the logistic map, we propose a simple predator-prey model where predators and prey adapt to each other, leading to the co-evolution of the system. The special dynamics observed in periodic windows contribute to the coexistence of multiple time scales, adding to the complexity of the system. Typical dynamics in ecosystems, such as the persistence and coexistence of population cycles and chaotic behaviors, the emergence of super-long transients, regime shifts, and the quantifying of resilience, are encapsulated within this single model. The simplicity of our model allows for detailed analysis, reinforcing its potential as a conceptual tool for understanding ecosystems deeply.

q-bio.PE

Mutation Order and Selection Shape Intratumor Heterogeneity in Tumor Evolution

Cancer progression often requires multiple driver mutations, but the same drivers may be acquired in different orders. How these pathways jointly shape tumor clonal structure remains unclear. We develop a multitype branching-process model in which malignant transformation requires two driver mutations, distinguishing malignant cells by mutation order and the independent transformation event that founded their clone. Under a successive exponential approximation, we establish point-process limits for pathway-specific clone sizes and derive a closed-form expression for the limiting expected Simpson's index of the combined malignant population. When both mutation orders yield malignant cells with the same net growth rate, the index decomposes into effective pathway weights, determined by mutation rates and birth-death dynamics at preceding stages, and within-pathway concentration terms, determined by intermediate-to-malignant growth-rate ratios. A driver's effect on heterogeneity thus depends critically on when it is acquired. A strong driver acquired early expands the intermediate lineage and increases the supply of independent malignant founders, whereas the same driver acquired last strengthens the growth and age advantage of early-founded malignant clones. Under additive fitness effects, these opposing mechanisms can produce a non-monotone relationship between selective advantage and clonal concentration. Threshold-like non-additive fitness effects can generate highly concentrated malignant populations, while order-dependent terminal fitness causes the faster-growing pathway to dominate asymptotically. These results show how mutation order, mutational accessibility, selection, and epistasis jointly determine lineage-level intratumor heterogeneity.

q-bio.PE

Phase transitions in microbial lineage trees

Microbial populations exhibit high cell-to-cell variability, which fundamentally shapes population behavior. A striking consequence is the existence of phase transitions, where small genetic or environmental changes trigger abrupt shifts in population dynamics. While biological phase transitions have often been proposed, connecting observed behavior to the underlying physics has remained challenging. We combine population genetics with statistical physics to show how phase transitions arise naturally in microbial populations. We highlight the existence of a first-order transition in a model of bacterial plasmid engineering and find a strict lower bound on the number of plasmids that can be stably maintained in a population.

q-bio.PE