Biology subjects

Redmond, A.

Publications and source records attributed to Redmond, A..

4 recordsLinked to original sources

bioRxiv2020

LINE elements are a reservoir of regulatory potential in mammalian genomes

To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in liver, brain, muscle, and testis from ten diverse mammals. The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species. Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome. HIGHLIGHTSO_LITissue-specific regulatory regions evolve faster than tissue-shared C_LIO_LISwitching promoter and enhancer regulatory roles is frequent in evolution C_LIO_LILINE L1s contribute to the evolution of tissue-specific regulatory regions C_LIO_LILINE L2s are associated with broad tissue activity and dynamic regulatory signatures C_LI

genomics↗

bioRxiv2020

Prevalence of Major Limb Loss (MLL) in Post conflict Acholi sub-region of Northern Uganda: Cross sectional study

BACKGROUNDThere is a widely reported preponderance of major limb loss in Northern Uganda, which is believed to have been caused in large part by prolonged civil war. Access to rehabilitation facilities is extremely limited, and there has never been a study to understand how many people have major limb loss, nor how many of them have had access to medical or rehabilitative services. AIMThe first prevalence study of disability and major limb loss in the region, and evaluated spatial patterns of cases of MLL. DESIGNCross-sectional survey. SETTINGThis research was undertaken in a community setting (at subjects homes). POPULATION7,864 randomly selected households throughout the Acholi Sub-Region of Northern Uganda. METHODSThis study comprised two questionnaires, the first to be completed by the head of every sampled household (n=7,864), and the second by any member of the household with major limb loss (n=181). Household locations were examined for spatial autocorrelation using Morans I statistic. The {chi}2 goodness of fit statistic was used to profile those with major limb loss in comparison with the underlying population. RESULTSWe conservatively estimate that there are c.10,117 people with major limb loss in the region who require long-term rehabilitation services (c.0.5% of the population), and c.150,512 people with disabilities other than MLL (c.8.2% of the population). People with major limb loss are spread throughout the region (as opposed to clustered in specific locations) and are disproportionately male, older and less well educated than the general population. CONCLUSIONThis research demonstrates, for the first time, the extent of the inadequacy of long-term rehabilitation services for those with major limb-loss in the study area. We provide new insight into the reasons that people are not accessing medical and rehabilitative services, and propose a way forward through the successful demonstration of an outreach clinic model. CLINICAL REHABILITATION IMPACTThe discovery of the spatial pattern of those with major limb loss, alongside the demonstration of the clinical outreach model, provides a compelling argument for the need of more such services and associated policy frameworks in remote and rural regions in the Global South. TIDIER ChecklistWe confirm that this manuscript conforms to the STROBE Checklist for Cross-Sectional Studies

pathology↗

bioRxiv2019

The whale shark genome reveals patterns of vertebrate gene family evolution

Chondrichthyes (cartilaginous fishes) are fundamental for understanding vertebrate evolution, yet their genomes are understudied. We report long-read sequencing of the whale shark genome to generate the best gapless chondrichthyan genome assembly yet with higher contig contiguity than all other cartilaginous fish genomes, and studied vertebrate genomic evolution of ancestral gene families, immunity, and gigantism. We found a major increase in gene families at the origin of gnathostomes (jawed vertebrates) independent of their genome duplication. We studied vertebrate pathogen recognition receptors (PRRs), which are key in initiating innate immune defense, and found diverse patterns of gene family evolution, demonstrating that adaptive immunity in gnathostomes did not fully displace germline-encoded PRR innovation. We also discovered a new Toll-like receptor (TLR29) and three NOD1 copies in the whale shark. We found chondrichthyan and giant vertebrate genomes had decreased substitution rates compared to other vertebrates, but gene family expansion rates varied among vertebrate giants, suggesting substitution and expansion rates of gene families are decoupled in vertebrate genomes. Finally, we found gene families that shifted in expansion rate in vertebrate giants were enriched for human cancer-related genes, consistent with gigantism requiring adaptations to suppress cancer.

genomics↗

bioRxiv2017

Lineage-specific rediploidization is a mechanism to explain time-lags between genome duplication and evolutionary diversification

The functional divergence of duplicate genes (ohnologues) retained from whole genome duplication (WGD) is thought to promote evolutionary diversification. However, species radiation and phenotypic diversification is often highly temporally-detached from WGD. Salmonid fish, whose ancestor experienced WGD by autotetraploidization ~95 Ma (i.e. Ss4R), fit such a time-lag model of post-WGD radiation, which occurred alongside a major delay in the rediploidization process. Here we propose a model called Lineage-specific Ohnologue Resolution (LORe) to address the phylogenetic and functional consequences of delayed rediploidization. Under LORe, speciation precedes rediploidization, allowing independent ohnologue divergence in sister lineages sharing an ancestral WGD event. Using cross-species sequence capture, phylogenomics and genome-wide analyses of ohnologue expression divergence, we demonstrate the major impact of LORe on salmonid evolution. One quarter of each salmonid genome, harbouring at least 4,500 ohnologues, has evolved under LORe, with rediploidization and functional divergence occurring on multiple independent occasions > 50 Myr post-WGD. We demonstrate the existence and regulatory divergence of many LORe ohnologues with functions in lineage-specific physiological adaptations that promoted salmonid species radiation. We show that LORe ohnologues are enriched for different functions than older ohnologues that began diverging in the salmonid ancestor. LORe has unappreciated significance as a nested component of post-WGD divergence that impacts the functional properties of genes, whilst providing ohnologues available solely for lineage-specific adaptation. Under LORe, which is predicted following many WGD events, the functional outcomes of WGD need not appear explosively, but can arise gradually over tens of Myr, promoting lineage-specific diversification regimes under prevailing ecological pressures.

genomics↗