arXiv subjects

Ester Lázaro

Publications and source records attributed to Ester Lázaro.

3 recordsLinked to original sources

arXiv2026

Bacteriophage Q$β$: Six Decades at the Frontier of Molecular and Viral Evolution

Bacteriophage Q$β$, first isolated in 1961, has served for more than six decades as a model system for molecular and viral evolution. The development of cell-free replication systems based on the Q$β$ replicase enabled the first demonstrations of Darwinian evolution in RNA molecules. In parallel, the phage's compact RNA genome, high mutation rate, and ease of propagation established Q$β$ as an exceptionally tractable model for studying viral evolution. The discovery of extensive genetic heterogeneity made of Q$β$ the first biological system in which molecular quasispecies theory found direct experimental support. Building on this foundation, decades of evolution experiments under thermal, ecological, and mutagenic pressures established how mutation, selection, epistasis, and population structure jointly shape adaptive trajectories. Deep sequencing has recently allowed the mutant spectrum of Q$β$ populations to be resolved as large, structured genotype networks, revealing a hierarchical organization around dominant sequences that generalizes classical mutation-selection balance to a dynamic process, and uncovering topological features shared with RNA viruses evolving within natural hosts. In parallel, the catalytic core of the Q$β$ replication system has been repurposed in synthetic biology to revive cell-free Darwinian evolution within compartmentalized, cell-like systems, opening new avenues for studying the origin and early evolution of life. Further recent work has pushed the phage into new experimental territories, including extreme, astrobiologically relevant environments and biotechnological platforms for peptide display. Together, these developments illustrate how a single bacteriophage has repeatedly anticipated and continues to clarify general principles of molecular, population, and ecological evolution.

q-bio.PE↗

arXiv2026

Shared quasispecies architecture in experimental and natural RNA virus populations

RNA viruses form genetically diverse populations structured as mutant spectra, or quasispecies, whose internal organization influences their evolutionary and adaptive dynamics. While genetic diversity has been extensively characterized, the structural organization of viral populations in sequence space remains less explored. Here, we compare genotype network architectures in two RNA viruses with markedly different evolutionary contexts: bacteriophage $Qβ$ evolving in controlled laboratory conditions and SARS-CoV-2 evolving within infected human hosts. Using deep sequencing data, we reconstruct the genotype network of mutationally coupled variants within viral populations and analyze their topological properties. Despite large differences in genome size, mutation rate, and ecological setting, both viruses exhibit a common organization: a highly abundant central haplotype surrounded by layers of variants of diminishing abundance as Hamming distance to the central haplotype increases. All reconstructed networks share qualitative and quantitative topological features, displaying a hierarchical structure. The robust organization of both populations under multiple conditions suggests that RNA viruses may share a common genotype network architecture governed by fundamental properties of sequence space and the generic mechanisms of replication and mutation. Genotype networks provide a unifying framework to describe viral population structure beyond conventional diversity measures and, by revealing how local constraints shape mutational search, offers insights into the predictability of viral evolution.

q-bio.PE↗

arXiv2024

Hierarchical genotype networks and incipient ecological speciation in Q$β$ phage quasispecies

Understanding how viral mutant spectra organize and explore genotype space is essential for unraveling the mechanisms driving evolution at the finest scale. Here we use deep-sequencing data of an amplicon in the A2 protein of the RNA bacteriophage Q$β$ to reconstruct genotype networks with tens of thousands of different haplotypes. The study of populations evolved under different temperature regimes uncovers generic topological features conditioned by fundamental structural motifs of genotype networks -- tetrahedrons, triangles, and squares -- that govern their local architecture. Mutant swarms display a hierarchical structure where sequences cluster around a highly connected and abundant sequence core that sustains population diversity. The immediate neighborhood of this core is comprehensively sampled, with no signs of selection, while a few mutations away sampling becomes dynamical and sparse, showing signs of purifying selection. By aggregating genotype networks from populations adapted to different temperatures, we capture the early stages of evolutionary divergence, with overlapping populations that remain connected through short mutational paths. Even at the time scale of these experiments, evolutionary pathways might be multiple, preventing the backward reconstruction of unique trajectories once mutations have been fixed. This analysis provides a detailed view of the local, fine-scale processes shaping viral quasispecies evolution and underscores the usefulness of genotype networks as an enlightening visualization of the organization of mutant swarms.

q-bio.PE↗