Biology subjects

Man, A. L.

Publications and source records attributed to Man, A. L..

3 recordsLinked to original sources

bioRxiv2025

Evolution of chromatin accessibility associated with traits of cichlid phenotypic diversity

The radiations of cichlid fishes in East African Lakes Victoria, Malawi, and Tanganyika showcase a remarkable example of rapid adaptive speciation, with over 2000 species evolving diverse morphological and ecological adaptations within the last few million years. Understanding the molecular basis of this phenotypic diversity remains a key challenge. Building on prior evidence of gene regulatory network (GRN) rewiring underpinning adaptive traits, we profiled chromatin accessibility (ATAC-seq) and matched transcriptomes across forebrain, retina, liver, and testis tissues in five representative cichlid species using optimised protocols. We show extensive divergence in chromatin accessibility corresponding to phylogenetic lineages and tissue identity, with many regulatory regions exhibiting accelerated nucleotide evolution. Transcription factor binding site (TFBS) variation correlates with both chromatin accessibility and differential gene expression, particularly in genes linked to sensory systems. Building on this, we reconstructed tissue- and species-specific GRNs and show that motif-supported network inference reveals pervasive but tissue-dependent rewiring, with the strongest candidate edges concentrated among accessible, highly expressed genes linked to adaptive traits. By integrating TF footprinting with regulatory motif turnover analyses, we demonstrate that dynamic nucleotide changes are associated with GRN rewiring, concordant with ecological niche and lineage-specific adaptations. Our findings highlight that regulatory variation at conserved and novel TFBSs associates with genes linked to phenotypic innovation across radiating and non-radiating East African cichlids. This study provides foundational epigenomic evidence linking GRN divergence to key mechanisms facilitating rapid adaptive diversification in this iconic vertebrate radiation.

evolutionary biology↗

bioRxiv2021

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

Alternative splicing (AS) is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing allows full-length transcript recovery and quantification, enabling transcript-level analysis of AS processes and how these change with cell state. Here, we utilise Oxford Nanopore Technologies sequencing to produce a custom annotation of a well-studied human neuroblastoma cell line and to characterise isoform expression and usage across differentiation. We identify many previously unannotated features, including a novel transcript of the voltage-gated calcium channel subunit gene, CACNA2D2. We show differential expression and usage of transcripts during differentiation, and identify a putative molecular regulator underlying this state change. Our work highlights the potential of long read sequencing to uncover previously unknown transcript diversity and mechanisms influencing alternative splicing.

genomics↗

bioRxiv2019

Faecal microbiota transplant from aged donor mice into young recipients affects spatial learning and memory

BackgroundThe gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems, however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients affected the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process, and related functions. Methods and FindingsYoung adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. Gut permeability, levels of circulating cytokines and expression of markers of microglia cells were also assessed. FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype, while gut permeability and levels of circulating cytokines remained unaffected. ConclusionsThese results demonstrate a direct effect of the age-associated shifts of the microbiota on protein expression and key functions of the central nervous system. Furthermore, these results additionally highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions in the elderly.

neuroscience↗