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Biology subjects

Farage, C.

Publications and source records attributed to Farage, C..

4 recordsLinked to original sources

A study of k-mer patterns within DNA molecules sequenced from a chondrite

The known tree of life occupies an infinitesimal region of the space of all mathematically possible evolutionary histories, yet our sequence analysis frameworks are implicitly calibrated to it and to its associated compositional and grammatical regularities. Here we analyze nucleic acid molecules sequenced from the Zag meteorite as part of a broader effort to understand how nucleic acid sequence composition and higher-order structure are shaped under chemically divergent environments. We characterize these sequences across multiple analytical layers, and show that they lack signatures of protein-coding organization, translational periodicity, or known biological grammar. At the same time, they deviate significantly from random or composition-only null models, displaying constrained complexity and low-dimensional structure in k-mer frequency space. Multiple tests place amplification and sequencing-driven artifacts and metagenomic contaminants at a low likelihood. Taken together, these findings indicate that the Zag sequences occupy an unusual region of sequence space that is not readily accounted for by known biological or technical models, thereby narrowing, but not resolving, the range of plausible explanations and motivating independent replication and further investigation.

bioinformatics↗

A food chain of ribozymes built on an ancestral strand

Molecular life forms in the prebiotic earth were capable of self-reproduction from basic building blocks. However, scarcity of building blocks likely led to the evolution of heterotrophic, predatory species. In this work we reconstruct a simple model of such interactions between RNA molecules, based on RNA strands found in sinkhole mineral pools in the Dead Sea. These RNA strands exhibited significant stability in this divergent chemical environment, and contained sequence motifs reminiscent of two ribozyme species, suggesting they could be ancestral to both. We built a system in which a single ancestral RNA strand serves as a limiting resource forming two different species of ribozymes that compete over it. One of these species is capable of metabolizing the other in order to free more of this resource, driving the assembly of additional copies of itself. This interaction resembles a rudimentary food chain, the dynamics of which is sensitive to environmental factors such as temperature and magnesium concentrations, with competitive advantage shifting between the species. Taken together, these findings highlight a hypothetical feature of prebiotic life, and hint at the possibility that heterotrophic RNA is a phenomenon that might still occur today in some unique geochemical niches, and even in the overlooked background of modern biological systems.

biophysics↗

Navigating a fine balance: point-mutant cheater viruses disrupt the viral replication cycle

Cheater viruses, alternatively denoted as defective interfering viruses, cannot replicate on their own yet replicate faster than the wild type (WT) when the two viruses coinfect the same cell. Cheaters must possess dual genetic features: a defect, which leads to their inability to infect cells on their own, and a selective advantage over WT during co-infection. Previously, we have discovered two point-mutant cheaters of the MS2 bacteriophage. Here, we set out to discover the possible repertoire of cheater MS2 viruses by performing experimental evolution at a very high multiplicity of infection (MOI). Our results revealed a third point-mutant cheater that arose in eight biological replicas. Each of the three cheaters disrupts the fine balance necessary for phage replication, in different ways that create a defect + advantage. We found that over time, the point mutant cheaters accumulate additional "helper" mutations, which alter other stages of the viral replication cycle, complementing the disruptions created by the original cheater. Intriguingly, cheater and helper mutations almost always reside in very close proximity on the genome. This region encodes for multiple functions: overlapping reading frames as well as overlapping RNA structures critical for transitioning from one stage to another in the viral replication cycle. This region of overlap explains the dual functions of cheaters, as one mutation can have pleiotropic effects. Overall, these findings underscore how viruses, whose dense genomes often have overlapping functions, can easily evolve point-mutant cheaters, and how cheaters can evolve to alter the intricate balance of the viral replication cycle.

evolutionary biology↗

A dynamical perspective to community detection in ecological networks

O_LIAnalysing how species interact in modules is a fundamental problem in network ecology. Theory shows that a modular network structure can reveal underlying dynamic ecological and evolutionary processes, influence dynamics that operate on the network and affect the stability of the ecological system. C_LIO_LIAlthough many ecological networks describe flows, such as biomass flows in food webs or disease trans-mission, most modularity analyses have ignored network flows, which can hinder our understanding of the interplay between structure and dynamics. C_LIO_LIHere we present Infomap, an established method based on network flows to the field of ecological networks. Infomap is a flexible tool that can identify modules in virtually any type of ecological network and is particularly useful for directed, weighted and multilayer networks. We illustrate how Infomap works on all these network types. We also provide a fully documented repository with additional ecological examples. Finally, to help researchers analyse their networks with Infomap, we introduce the open source R package infomapecology. C_LIO_LIAnalysing flow-based modularity is useful across ecology and transcends to other biological and non-biological disciplines. A dynamic approach for detecting modular structure has strong potential to provide new insights into the organisation of ecological networks. C_LI

ecology↗