Genomic comparisons reveal biogeographic and anthropogenic impacts in the koala (Phascolarctos cinereus): a dietary-specialist species distributed across heterogeneous environments

The Australian koala is an iconic marsupial with highly specific dietary requirements distributed across heterogeneous environments, over a large geographic range. The distribution and genetic structure of koala populations has been heavily influenced by human actions, specifically habitat modification, hunting and translocation of koalas. There is currently limited information on population diversity and gene flow at a species-wide scale, or with consideration to the potential impacts of local adaptation. Using species-wide sampling across heterogeneous environments, and high-density genome-wide markers (SNPs and PAVs), we show that most koala populations display levels of diversity comparable to other outbred species, except for those populations impacted by population reductions. Genetic clustering analysis and phylogenetic reconstruction reveals a lack of support for current taxonomic classification of three koala subspecies, with only a single evolutionary significant unit supported. Furthermore, similar to 70% of genetic variance is accounted for at the individual level. The Sydney Basin region is highlighted as a unique reservoir of genetic diversity, having higher diversity levels (i.e., Blue Mountains region; AvHe(corr)-0.20, PL% = 68.6). Broad-scale population differentiation is primarily driven by an isolation by distance genetic structure model (49% of genetic variance), with clinal local adaptation corresponding to habitat bioregions. Signatures of selection were detected between bioregions, with no single region returning evidence of strong selection. The results of this study show that although the koala is widely considered to be a dietary-specialist species, this apparent specialisation has not limited the koala's ability to maintain gene flow and adapt across divergent environments as long as the required food source is available

Laminin N-terminus alpha 31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model

Laminins (LMs) are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non‐laminin but netrin‐like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing. In vitro functional studies have shown that LaNt α31 can influence numerous aspects of epithelial cell behavior via modifying matrix organization, suggesting a new model of laminin auto‐regulation. However, the function of this protein has not been established in vivo. Here, a mouse transgenic line was generated using the ubiquitin C promoter to drive inducible expression of LaNt α31. When expression was induced at embryonic day 15.5, LaNt α31 transgenic animals were not viable at birth, exhibiting localized regions of erythema. Histologically, the most striking defect was widespread evidence of extravascular bleeding across multiple tissues. Additionally, LaNt α31 transgene expressing animals exhibited kidney epithelial detachment, tubular dilation, disruption of the epidermal basal cell layer and of the hair follicle outer root sheath, and ~50% reduction of cell numbers in the liver, associated with depletion of hematopoietic erythrocytic foci. These findings provide the first in vivo evidence that LaNt α31 can influence tissue morphogenesis

Relationship between two sequence variations in the gene for peroxisome proliferator-activated receptor-gamma and plasma homocysteine concentration. Health in men study

The concentration of circulating homocysteine has been associated with a variety of diseases, including myocardial infarction, stroke, venous thrombosis and cognitive decline. Genetic variation has been demonstrated to play an important role in determining plasma homocysteine, however, the genes involved are incompletely understood. Ligation of the transcription factor peroxisome proliferator-activated gamma (PPARG) has been demonstrated to lower plasma homocysteine. We examined the association of two sequence variations in PPARG with plasma concentrations of homocysteine in a population-based study of 3,875 elderly men. PPARG c.34G > C and PPARG c.1347C > T sequence variations were determined by real-time quantitative PCR and related to logarithm transformed homocysteine concentrations using linear regression, adjusting for the co-variants age, renal function, smoking, coronary heart disease, waist to hip ratio, diabetes, hypertension and MTHFR g.677C > T sequence variation. Median plasma homocysteine concentration was 10% higher in men who were homozygous for the rare allelic variation in PPARG c.34G > C and PPARG c.1347C > T by comparison to those who had wild type sequence variation. PPARG c.1347C > T (β = 0.038, P = 0.01 recessive model; β = 0.036, P = 0.02 dominant model) sequence variation was positively associated with homocysteine concentration after adjusting for co-variants. The two PPARG sequence variations were in linkage disequilibrium and the common haplotype was associated with lower plasma homocysteine (P = 0.005). Our findings demonstrate a new genotypic association with plasma homocysteine. Replication will be required in other cohorts