Biology subjects

Liston, A.

Publications and source records attributed to Liston, A..

4 recordsLinked to original sources

bioRxiv2018

Machine learning identifies the immunological signature of Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, with a strongly debated pathophysiological origin. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. Here we profiled the adaptive immune system of 85 JIA patients and 43 age-matched controls, identifying immunological changes unique to JIA and others common across a broad spectrum of childhood inflammatory diseases. The JIA immune signature was shared between clinically distinct subsets, but was accentuated in the systemic JIA patients and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and JIA patients, machine learning analysis of the dataset proved capable of diagnosis of JIA patients with ~90% accuracy. These results pave the way for large-scale longitudinal studies of JIA, where machine learning could be used to predict immune signatures that correspond to treatment response group.

immunology↗

bioRxiv2018

Mice deficient in nucleoporin Nup210 develop peripheral T cell alterations

The nucleopore is an essential structure of the eukaryotic cell, regulating passage between the nucleus and cytoplasm. While individual functions of core nucleopore proteins have been identified, the role of other components, such as Nup210, are poorly defined. Here, through the use of an unbiased ENU mutagenesis screen for mutations effecting the peripheral T cell compartment, we identified a Nup210 mutation in a mouse strain with altered CD4 / CD8 T cell ratios. Through the generation of Nup210 knockout mice we identified Nup210 as having a T cell-intrinsic function in the peripheral homeostasis of T cells. Remarkably, despite the deep evolutionary conservation of this key nucleopore complex member, no other major phenotypes developed, with viable and healthy knockout mice. These results identify Nup210 as an important nucleopore complex component for peripheral T cells, and raise further questions of why this nucleopore component shows deep evolutionary conservation despite seemingly redundant functions in most cell types.

immunology↗

bioRxiv2018

Both functional trait divergence and trait plasticity confer polyploid advantage in changing environments

Polyploidy, or whole genome duplication, exists in all eukaryotes and is thought to drive ecological and evolutionary success especially in plants. The mechanisms of polyploid success in ecologically relevant contexts, however, remain largely unknown. Here we conducted an extensive test of functional trait divergence and trait plasticity in conferring polyploid fitness advantage in changing environments by growing clonal replicates of a worldwide genotype collection of six polyploid and five diploid wild strawberry (Fragaria) species in three climatically different common gardens. Among leaf functional traits, we detected divergence in means but not plasticities between polyploids and diploids, suggesting that increased genomic redundancy does not necessarily translate into broader phenotypic amplitude in polyploids. Across the heterogeneous garden environments, however, polyploids exhibited fitness advantage, which was conferred by both trait means and adaptive trait plasticities, supporting a jack-and-master hypothesis for polyploids. Our findings provide unparalleled insight into the prevalence and persistence of polyploidization.

ecology↗

bioRxiv2017

Repeated translocation of a gene cassette drives sex chromosome turnover in strawberries

Turnovers of sex-determining systems represent important diversifying forces across eukaryotes. Shifts in sex chromosomes, but conservation of the master sex-determining genes, characterize distantly-related animal lineages. Yet in plants, where separate sexes have evolved repeatedly and sex chromosomes are typically homomorphic, we do not know whether such translocations drive turnovers within closely related groups. This phenomenon can only be demonstrated by identifying sex-associated nucleotide sequences, still largely unknown in plants. The wild North American octoploid strawberries (Fragaria) exhibit separate sexes (dioecy) with homomorphic, female heterogametic (ZW) inheritance, yet sex maps to at least three different chromosomes. To characterize these turnovers, we sequenced the complete genomes of 60 plants of known sex from five Fragaria taxa. We identified 31-mers unique to females and assembled their reads into contigs. Remarkably, a short (13 kb) sequence is observed in nearly all females and never in male-fertile individuals, implicating it as the sex-determining region (SDR). This female-specific \"SDR cassette\" contains both a gene with a known role in fruit and pollen production and a novel retrogene absent on Z and autosomal chromosomes. Comparing SDR cassettes across taxa reveals a history of repeated translocation, which can be ordered temporally due to the capture of adjacent sequence with each successive move. The accumulation of these \"souvenirs\" suggests an adaptive basis for the expanding (up to at least 23 kb) hemizygous region. This is the first plant SDR known to be translocated, and it suggests a new mechanism (\"move-lock-grow\") for expansion and diversification of incipient sex chromosomes.\n\nSignificance StatementSex chromosomes frequently restructure themselves during organismal evolution, often becoming highly differentiated. This dynamic process is poorly understood for most taxa, especially during the early stages typical of many dioecious plants. In wild strawberries, a sex-determining region of DNA has repeatedly changed its genomic location, each time increasing the size of the hemizygous female-specific sequence. This observation shows for the first time that plant sex regions can \"jump\", and suggests that this phenomenon may be adaptive by gathering and locking new genes into linkage with sex. This conserved and presumed causal sequence with a variable genomic location presents a unique opportunity to understand how sex chromosomes first begin to differentiate.

evolutionary biology↗