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Biology subjects

Davis, L. R.

Publications and source records attributed to Davis, L. R..

4 recordsLinked to original sources

An epigenetic palimpsest: the King penguin's blood methylome reveals conserved hematopoietic ageing

Age-associated DNA methylation is conserved across vertebrates, but whether epigenetic ageing reflects cellular ageing programmes or age-dependent shifts in cell composition remains unresolved. Here, using 126 whole-blood methylomes from known-age King penguins (Aptenodytes patagonicus), we exploit a vertebrate system in which nucleated erythrocytes dominate peripheral blood, minimizing the influence of leukocyte heterogeneity. We identify a core set of 409 ageing-associated genes showing lifelong, clock-like methylation change. These genes are strongly enriched for regulators of hematopoietic stem and progenitor cell (HSPC) function and niche communication. Integration of methylome, transcriptome and chromatin-accessibility data reveals that many of the strongest ageing signals derive from genes inactive in mature erythrocytes, consistent with the persistence of epigenetic states from ancestral hematopoietic progenitors. A comparison with methylation profiles from 1,501 humans identified a conserved cross-species subset of ageing genes, and a human epigenetic age model constructed solely from orthologues of penguin ageing genes predicts chronological age with high accuracy while remaining largely insensitive to blood cell composition. We propose that blood epigenetic ageing signatures contain a long-lived cellular memory of stem-cell ageing, that may represent an evolutionarily ancient layer of the vertebrate ageing process.

systems biology↗

The BEAC, an epigenetic clock for birds

Epigenetic clocks are powerful tools for estimating both chronological and biological age, enabling the integration of age information into population monitoring, demographic modelling, and research on the ecophysiology and evolution of ageing. Most epigenetic clocks so far have been developed for mammals: here, we present the Bird Epigenetic Ageing Clock (BEAC) for estimating chronological age in avian species. BEAC was established based on genome-wide enzymatic methylation sequencing data of known-age king penguins (Aptenodytes patagonicus), and validated in nine other bird species. The BEAC collects age-informative signals into a bisulfite amplicon sequencing panel of 24 primer pairs, providing a highly accurate and cost-effective alternative to sequencing-intensive approaches. It achieved strong predictive performance in independent king penguin training (R{superscript 2}=0.88; MAE=1.7 years, n=78) and testing data (R{superscript 2}=0.79; MAE=2.3 years, n=41), with negligible batch effects, high longitudinal consistency, and resilience to reduced sample size or missing loci. Importantly, cross-species validation across 180 samples showed that BEAC reliably captures age-associated methylation signals in nine additional bird species across seven clades, demonstrating that a single set of loci can be predictive of ageing across multiple different bird species. BEAC offers a flexible, empirically validated tool and a transferable framework for developing epigenetic clocks in avian species, providing a highly valuable resource for eco-evolutionary studies of ageing in wild species.

molecular biology↗

Gene function is a driver of signaling pathway evolution following whole genome 5 duplication

The genome of many plant and animal species are heavily influenced by ancestral whole genome duplication (WGD) events. These events transform the regulation and function of gene networks, yet the evolutionary forces at work on duplicated genomes are not fully understood. Genes involved in cell surface signaling pathways are commonly retained following WGD. To understand the mechanisms driving functional evolution of duplicated cell signaling pathways, we performed the activin receptor signaling pathway in rainbow trout (RBT). Rainbow trout are a model salmonid species that exhibit a duplicated genome as a result of an ancestral WGD that occurred in all teleost fish, and a second more recent WGD found in salmonid fishes. This makes RBT a powerful system for studying ohnolog evolution in a single species. We observed that regulation of the duplicated activin receptor signaling pathway is commonly driven by tissue-specific expression of inhibitors and ligands along with the subfunctionalization of ligand ohnologs. Evidence suggests that for inhibitors and R-Smad signaling molecules, there is ongoing pressure to establish a single copy state which may be driven, in part, by regulatory suppression of select ohnologs. The core transmembrane receptors and Co-Smad signaling cascade members are high duplicated yet exhibit contrasting expression dynamics where receptors tend to share expression across tissues while dominance of a single ohnolog is common for the Smad4, Co-Smad gene family. Our findings provide support for a generalized model where gene function and gene dosage have a complementary role in ohnolog evolution following WGD.

evolutionary biology↗

Chromosome-level genome assembly for the Aldabra giant tortoise enables insights into the genetic health of a threatened population

The Aldabra giant tortoise (Aldabrachelys gigantea) is one of only two giant tortoise species left in the world. The species is endemic to Aldabra Atoll in Seychelles and is considered vulnerable due to its limited distribution and threats posed by climate change. Genomic resources for A. gigantea are lacking, hampering conservation efforts focused on both wild and ex-situ populations. A high-quality genome would also open avenues to investigate the genetic basis of the exceptionally long lifespan. Here, we produced the first chromosome-level de novo genome assembly of A. gigantea using PacBio High-Fidelity sequencing and high-throughput chromosome conformation capture (Hi-C). We produced a 2.37 Gbp assembly with a scaffold N50 of 148.6 Mbp and a resolution into 26 chromosomes. RNAseq-assisted gene model prediction identified 23,953 protein-coding genes and 1.1 Gbp of repetitive sequences. Synteny analyses among turtle genomes revealed high levels of chromosomal collinearity even among distantly related taxa. We also performed a low-coverage re-sequencing of 30 individuals from wild populations and two zoo individuals. Our genome-wide population structure analyses detected genetic population structure in the wild and identified the most likely origin of the zoo-housed individuals. The high-quality chromosome-level reference genome for A. gigantea is one of the most complete turtle genomes available. It is a powerful tool to assess the population structure in the wild population and reveal the geographic origins of ex-situ individuals relevant for genetic diversity management and rewilding efforts.

genomics↗