Biology subjects

Larkin, A.

Publications and source records attributed to Larkin, A..

7 recordsLinked to original sources

bioRxiv2026

Decadal signatures of seasonal and ENSO-driven selection in microbial populations in distant oceans

Despite the crucial role of the ocean microbiome for global ecosystem processes, its response to global change remains poorly understood. Global change will exert selection on microbial species through changes in the genetic composition of their populations, favouring strains that are better adapted to new conditions. Analyzing long-term genomic variation in microbial populations inhabiting climatically comparable but oceanographically distinct regions may provide insights into their responses to future environmental conditions. We analyzed coastal marine microbiomes from two distant long-term observatories with Mediterranean-type climates but contrasting oceanographic regimes: the Blanes Bay Microbial Observatory (BBMO; Northwestern Mediterranean Sea) and the Microbes in the Coastal Region of Orange County (MiCRO; California coast, Pacific Ocean). Sampling conducted at least monthly during 15 and 10 years, respectively, yielded 1,535 Metagenome-Assembled Genomes (MAGs) in BBMO and 1,068 MAGs plus 187 Single-Amplified Genomes (SAGs) in MiCRO. Among these, we found 250 genomes with intraspecific (>95% genome similarity) representatives occurring at both sites. In contrast, at the strain-level threshold ([≥]99% genome similarity), only 13 BBMO genomes matched 15 closely related representatives in MiCRO. As genome similarity increased, we observed a shift from cosmopolitan to more coastal distributions and a slight increase in genome size, pointing to niche adaptation. Across both time series, we observed widespread seasonal population structure, with most genomes (~70%) showing significant seasonal structuring of variant composition. Moreover, in MiCRO, ~76% of the tested genomes also showed El Nino Southern Oscillation (ENSO)-associated structure in variant composition beyond seasonal effects. Focusing on a Prochlorococcus genome with intraspecific representatives at both locations (>96% genome similarity) we further found recurrent seasonal mutations and non-synonymous to synonymous mutation ratios (pN/pS) from multiple genes, together with signatures of positive selection (higher pN/pS) coinciding with El Nino events in MiCRO. This suggests an imprint of ENSO in marine microbial populations. Thus, beyond seasonality, long-term climatic oscillations may shape microbial populations. This has implications for understanding how the ocean microbiome will respond to long-term environmental change and prolonged disturbances through population-level genomic variation.

microbiology↗

bioRxiv2026

Hydrogen sulfide dynamically upregulates copper uptake and localization

The reactivity of copper, an essential micronutrient that undergoes facile cycling between Cu1+ and Cu2+ redox states, is carefully controlled within the confines of protein binding sites, and by sequestration in storage vesicles, or harnessed to kill pathogens by active pumping of Cu1+ into phagosomes. We have discovered that hydrogen sulfide, a signaling metabolite generated in copious quantities at the host-microbiome interface, upregulates Cu accumulation in diffusely dispersed puncta across the cell, as visualized by X-ray fluorescence microscopy. The Cu is predominantly in the Cu2+ state with oxygen/nitrogen ligands. Cu import occurs via the non- canonical ZNT1 transporter, while export, following sulfide withdrawal, is ATP7A-dependent. Cu accumulates at the apices of colon crypts in a mouse model of elevated sulfide exposure due to SQOR deficiency in the intestinal epithelium, establishing in vivo relevance. Our study reveals that sulfide is a dynamic regulator of the Cu pool, stimulating Cu2+ influx into highly concentrated puncta.

cell biology↗

bioRxiv2026

Defining the Candidozyma auris pan-genome and essentiality

Candidozyma auris is a multi-drug resistant fungal pathogen that causes hospital outbreaks, but genetic variation and gene function in this organism remain undercharacterized. Here, we performed pangenome analysis on 695 genetically representative isolates of C. auris and found that only 2.6% of gene families varied in their presence, mainly consisting of gene loss events or clade-specific genes, highlighting the clonal nature of these strains. Using microbial genome-wide association, we identified two loci associated with altered keratinocyte adherence, including genes with unknown function. To look broadly at gene function, we developed a genome-scale insertional mutagenesis approach and identified 614 high-confidence essential genes. Nearly one-third of these genes exhibited divergent essentiality compared to the model yeasts Candida albicans and Saccharomyces cerevisiae. Together, this study highlights organism-specific biology and provides a comprehensive resource for identifying species-specific determinants of virulence and targets for antifungal drug development.

microbiology↗

bioRxiv2023

Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.

HP1 proteins are essential for establishing and maintaining transcriptionally silent heterochromatin. They dimerize, forming a binding interface to recruit diverse chromatin-associated factors. HP1 proteins are specialized and rapidly evolve, but the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impacts epigenetic inheritance, we performed a targeted mutagenesis screen of the S. pombe HP1 homolog, Swi6. Substitutions within an auxiliary surface adjacent to the HP1 dimerization interface produced Swi6 variants with divergent maintenance properties. Remarkably, substitutions at a single amino acid position led to the persistent gain or loss of epigenetic inheritance. These substitutions increased Swi6 chromatin occupancy in vivo and altered Swi6-protein interactions that reprogram H3K9me maintenance. We show that relatively minor changes in Swi6 amino acid composition can lead to profound changes in epigenetic inheritance which provides a redundant mechanism to evolve novel effector specificity.

molecular biology↗

bioRxiv2023

Mapping the dynamics of epigenetic adaptation

A classical and well-established mechanism that enables cells to adapt to new and adverse conditions is the acquisition of beneficial genetic mutations. Much less is known about epigenetic mechanisms that allow cells to develop novel and adaptive phenotypes without altering their genetic blueprint. It has been recently proposed that histone modifications, such as heterochromatin-defining H3K9 methylation (H3K9me), normally reserved to maintain genome integrity, can be redistributed across the genome to establish new and potentially adaptive phenotypes. To uncover the dynamics of this process, we developed a precision engineered genetic approach to trigger H3K9me redistribution on-demand in fission yeast. This enabled us to trace genome-scale RNA and chromatin changes over time prior to and during adaptation in long-term continuous cultures. Establishing adaptive H3K9me occurs over remarkably slow time-scales relative to the initiating stress. During this time, we captured dynamic H3K9me redistribution events ultimately leading to cells converging on an optimal adaptive solution. Upon removal of stress, cells relax to new transcriptional and chromatin states rather than revert to their initial (ground) state, establishing a tunable memory for a future adaptive epigenetic response. Collectively, our tools uncover the slow kinetics of epigenetic adaptation that allow cells to search for and heritably encode adaptive solutions, with implications for drug resistance and response to infection.

genetics↗

bioRxiv2023

The establishment of HP1-independent heterochromatin reveals an essential role for HP1 proteins in maintaining epigenetic memory

H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. HP1 proteins are required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S.pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.

genetics↗

bioRxiv2018

Comparing the Rat Grimace Scale and a composite behaviour score in rats

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram reliant on postural changes), are both promising pain assessment methods. Both scales have been used to assess pain in a laparotomy model, however, they have never been compared directly and the knowledge of how different analgesics may affect these two scales is limited. This study aimed to provide a comparison to discriminate the temporal and analgesic response in a laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block randomized to receive saline, meloxicam (2 mg/kg) or buprenorphine (0.05 mg/kg) 30 minutes before a laparotomy model. Rats were video-recorded before surgery (BL) and at 30, 150, 270, and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, blinded observer. Both CBS and RGS scores increased significantly at all post surgical timepoints in the saline group. Post-surgical CBS scores did not increase significantly above baseline levels in the groups given meloxicam or buprenorphine. However, the RGS scores only remained low in the buprenorphine group while scores increased significantly in the meloxicam group, to a similar degree as in the saline group. These findings suggest that the CBS is more sensitive to the analgesic effects of NSAIDs than the RGS.

animal behavior and cognition↗