Evolutionary origin and development of snake fangs

Many advanced snakes use fangs-specialized teeth associated with a venom gland-to introduce venom into prey or attacker. Various front- and rear-fanged groups are recognized, according to whether their fangs are positioned anterior (for example cobras and vipers) or posterior (for example grass snakes) in the upper jaw. A fundamental controversy in snake evolution is whether or not front and rear fangs share the same evolutionary and developmental origin. Resolving this controversy could identify a major evolutionary transition underlying the massive radiation of advanced snakes, and the associated developmental events. Here we examine this issue by visualizing the tooth-forming epithelium in the upper jaw of 96 snake embryos, covering eight species. We use the sonic hedgehog gene as a marker, and three-dimensionally reconstruct the development in 41 of the embryos. We show that front fangs develop from the posterior end of the upper jaw, and are strikingly similar in morphogenesis to rear fangs. This is consistent with their being homologous. In front-fanged snakes, the anterior part of the upper jaw lacks sonic hedgehog expression, and ontogenetic allometry displaces the fang from its posterior developmental origin to its adult front position-consistent with an ancestral posterior position of the front fang. In rear-fanged snakes, the fangs develop from an independent posterior dental lamina and retain their posterior position. In light of our findings, we put forward a new model for the evolution of snake fangs: a posterior subregion of the tooth-forming epithelium became developmentally uncoupled from the remaining dentition, which allowed the posterior teeth to evolve independently and in close association with the venom gland, becoming highly modified in different lineages. This developmental event could have facilitated the massive radiation of advanced snakes in the Cenozoic era, resulting in the spectacular diversity of snakes seen today.     

Whole-genome analysis informs breast cancer response to aromatase inhibition

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.     

A mutation in APP protects against Alzheimer's disease and age-related cognitive decline

The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.     

Ocean nutrient ratios governed by plankton biogeography

The major nutrients nitrate and phosphate have one of the strongest correlations in the sea, with a slope similar to the average nitrogen (N) to phosphorus (P) content of plankton biomass (N/P = 16:1). The processes through which this global relationship emerges despite the wide range of N/P ratios at the organism level are not known. Here we use an ocean circulation model and observed nutrient distributions to show that the N/P ratio of biological nutrient removal varies across latitude in Southern Ocean surface waters, from 12:1 in the polar ocean to 20:1 in the sub-Antarctic zone. These variations are governed by regional differences in the species composition of the plankton community. The covariation of dissolved nitrate and phosphate is maintained by ocean circulation, which mixes the shallow subsurface nutrients between distinct biogeographic provinces. Climate-driven shifts in these marine biomes may alter the mean N/P ratio and the associated carbon export by Southern Ocean ecosystems.     

Recent decline in the global land evapotranspiration trend due to limited moisture supply

More than half of the solar energy absorbed by land surfaces is currently used to evaporate water. Climate change is expected to intensify the hydrological cycle and to alter evapotranspiration, with implications for ecosystem services and feedback to regional and global climate. Evapotranspiration changes may already be under way, but direct observational constraints are lacking at the global scale. Until such evidence is available, changes in the water cycle on land?a key diagnostic criterion of the effects of climate change and variability?remain uncertain. Here we provide a data-driven estimate of global land evapotranspiration from 1982 to 2008, compiled using a global monitoring network, meteorological and remote-sensing observations, and a machine-learning algorithm. In addition, we have assessed evapotranspiration variations over the same time period using an ensemble of process-based land-surface models. Our results suggest that global annual evapotranspiration increased on average by 7.1?±?1.0?millimetres per year per decade from 1982 to 1997. After that, coincident with the last major El Ni?o event in 1998, the global evapotranspiration increase seems to have ceased until 2008. This change was driven primarily by moisture limitation in the Southern Hemisphere, particularly Africa and Australia. In these regions, microwave satellite observations indicate that soil moisture decreased from 1998 to 2008. Hence, increasing soil-moisture limitations on evapotranspiration largely explain the recent decline of the global land-evapotranspiration trend. Whether the changing behaviour of evapotranspiration is representative of natural climate variability or reflects a more permanent reorganization of the land water cycle is a key question for earth system science.