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Stuart, A. J.

Publications and source records attributed to Stuart, A. J..

3 recordsLinked to original sources

Ancient persistence and newfound diversity of CR1-group retrotransposons across chordates

Retrotransposons are mobile, repetitive DNA sequences that are ubiquitous across eukaryotes and widely recognised as key drivers of both gene and genome evolution. The CR1 group of retrotransposons is thought to have been present in the most recent common ancestor of chordates [~]560 mya, and is the dominant retrotransposon in the majority of chordate species. The advent of long-read sequencing technologies has enabled the assembly of high-quality genomes from representatives of almost all major chordate orders, enabling comparative analysis with deeply divergent species. To better understand the composition of CR1-group elements (CGEs) in chordates, we systematically characterised full-length, recently active transposable elements across representative species from every available extant order of chordate. Our analysis uncovered previously unknown phylogenetic relationships of CGEs within and between species and has pushed back the origin of certain CR1-group subclades by tens of millions of years. Additionally, entirely novel elements with no close relatives in existing databases were uncovered within several of the species analysed. We also detected numerous putative horizontal transfer events, many of which had not been previously documented. Overall, this investigation has provided the first chordate-wide analysis of an element that is historically understudied yet plays a pivotal role in genome biology and evolution.

evolutionary biology↗

Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia

Replicative senescence, a powerful tumor suppressor pathway, occurs when a few critically-short telomeres activate the DNA damage response (DDR). We show that ATM is the sole DDR kinase responsible for the induction and maintenance of replicative senescence and that ATM inhibition can induce normal cell divisions in senescent cells. Compared to non-physiological atmospheric ([~]20%) oxygen, cells grown at physiological (3%) oxygen were more tolerant to critically-short telomeres, explaining their extended replicative lifespan. We show that this tolerance is due to attenuation of the ATM response to double-strand breaks (DSBs) and unprotected telomeres. Our data indicate that the reduced ATM response to DSBs at 3% oxygen is due to increased ROS, which induces disulfide-bridges in ATM, generating crosslinked ATM dimers that do not respond to DSBs. This regulation of cellular lifespan through attenuation of ATM at physiological oxygen has implications for tumor suppression through telomere shortening.

cell biology↗

Late Pleistocene palaeoecology and phylogeography of woolly rhinoceroses

The woolly rhinoceros (Coelodonta antiquitatis) was a cold-adapted herbivore, widely distributed from western Europe to north-east Siberia during the Late Pleistocene. Previous studies associate the extinction of the species ~14,000 years before present to climatic and vegetational changes, and suggest that later survival of populations in north-east Siberia may relate to the later persistence of open vegetation in that region. Here, we analyzed carbon ({delta}13C) and nitrogen ({delta}15N) stable isotopes and mitochondrial DNA sequences to elucidate the evolutionary ecology of the species. Our dataset comprised 286 woolly rhinoceros isotopic records, including 192 unpublished records, from across the species range, dating from >58,600 14C years to ~14,000 years before present. Crucially, we present the first 71 isotopic records available to date of the 15,000 years preceding woolly rhinoceros extinction. The data reveal ecological flexibility and geographical variation in woolly rhinoceros stable isotope compositions through time. In north-east Siberia, we detected{delta} 15N stability through time. This could reflect long-term environmental stability, and might have enabled the later survival of the species in the region. To further investigate the palaeoecology of woolly rhinoceroses, we compared their isotopic compositions with that of other contemporary herbivores. This analysis suggests possible niche partitioning between woolly rhinoceros and both horse (Equus spp.) and woolly mammoth (Mammuthus primigenius), and isotopic similarities between woolly rhinoceros and both musk ox (Ovibos moschatus) and saiga (Saiga tatarica) at different points in time. To provide phylogeographical context to the isotopic data, we analyzed 61 published mitochondrial control region sequences. The data show a lack of geographic structuring; we found three haplogroups with overlapping distributions, all of which show a signal of expansion during the Last Glacial Maximum. Furthermore, our genetic findings support the notion that environmental stability in Siberia had an impact on the paleoecology of woolly rhinoceroses in the region. Our study highlights the utility of combining stable isotopic records with ancient DNA to advance our knowledge of the evolutionary ecology of past populations and extinct species.

evolutionary biology↗