Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan

Item does not contain fulltextThe BubR1 gene encodes for a mitotic regulator that ensures accurate segregation of chromosomes through its role in the mitotic checkpoint and the establishment of proper microtubule-kinetochore attachments. Germline mutations that reduce BubR1 abundance cause aneuploidy, shorten lifespan and induce premature ageing phenotypes and cancer in both humans and mice. A reduced BubR1 expression level is also a feature of chronological ageing, but whether this age-related decline has biological consequences is unknown. Using a transgenic approach in mice, we show that sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorigenesis, even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras. We find that BubR1 overabundance exerts its protective effect by correcting mitotic checkpoint impairment and microtubule-kinetochore attachment defects. Furthermore, sustained high-level expression of BubR1 extends lifespan and delays age-related deterioration and aneuploidy in several tissues. Collectively, these data uncover a generalized function for BubR1 in counteracting defects that cause whole-chromosome instability and suggest that modulating BubR1 provides a unique opportunity to extend healthy lifespan

Biogeographic trends in Antarctic lake communities

The basic biogeographic zones proposed many years ago – the Subantarctic islands, Maritime Antarctica and Continental Antarctica – continue to hold up, though they cannot be seen as absolute dividers of biodiversity. For example, subantarctic Macquarie Island appears to be biogeographically separate from the islands of the Kerguelen Province, and on the continent there are species that are present in lakes of more than one zone. Furthermore, there are numerous lake environments that have yet to be investigated, and it is probable that some of these lakes could turn up surprises that will bring into question these basic divisions. An important question to be answered is whether these biogeographic zones reflect climate attributes, or whether they were moulded long ago by barriers to dispersal. Again, our imperfect knowledge of Antarctic lacustrine biogeography means that this question cannot at present be answered. However, as discussed elsewhere in this volume (Chown and Convey), there are indications of a strong biogeographical boundary for terrestrial species between the Maritime and Continental Antarctic zones. A palaeolimnological approach will assist in answering this question: understanding how Antarctic biogeography has developed through time will provide necessary insights into current distributions. A prime example is the occurrence of the copepod Boeckella poppei in Beaver Lake. Pugh et al. (2002) initially concluded that this species was an anthropogenic introduction, then Bayly et al. (2003) provided morphological evidence for long habitation in the area of Beaver Lake. Recent palaeolimnological work has shown that the species has been present in nearby Lake Terrasovoje for at least 9000 yrs (L. Cromer, A. Bissett, J. Gibson and K. Swadling, unpublished data). Even though this lake has only existed in the Holocene, cosmogenic exposure dates in the same area of exposed rock can exceed 106 years (D. Gore and D. White, personal communication). From these observations it can be concluded that Boeckella poppei has been associated with the Beaver Lake area for at least the entire Holocene and probably well back into the Pleistocene, and that its occurrence outside its ‘preferred’ biogeographical zone (Maritime Antarctica) is not a reflection of current climate, rather of history. The majority of our knowledge regarding Antarctic lacustrine biodiversity and biogeography has come from classic taxonomic studies, where the morphology (or biochemistry for bacteria) has been of greatest importance. In many cases this has led to questionable identification, correct identification of species is paramount if the true biodiversity and biogeography of Antarctica is to be deduced. It is only in the last few years that the more objective approach of molecular genetics has been applied to Antarctic lacustrine organisms, and then only for more cryptic groups, such as bacteria and cyanobacteria. As more samples and organisms are studied by these methods it is likely that new relationships between species distributions will be found. Due to the limited number of species in Antarctica (compared to more temperate zones), it may be possible in the future to record the make-up of selected genes of most, if not all, of the biota, which will allow more precise analysis. There is increasing evidence for endemism amongst the inhabitants of lakes both on the Antarctic continent and the subantarctic islands, from bacteria to crustacea. Use of molecular genetic techniques to identify more cryptic species will most likely add to the list of putative endemics. It is clear, however, that recent colonisation and current climate also play important roles in the distribution of the biota, as most of the lakes in Antarctica are of relatively recent (Holocene) origin. Colonising species have to be adapted to transport from source areas, which can either involve inter- or intra-continental movement, as well as survival on arrival at potential habitat. Flexibility in nutritional and habitat requirements is an important factor in determining whether a species will be a successful coloniser. The buffering to environmental extremes provided by the liquid water habitat means that conditions further south will not be as harsh as those experienced by their terrestrial counterparts. As the climate changes in the future, it will be interesting to note the effects of these changes on the lacustrine biota. Will new species colonise the Antarctic Peninsula where temperatures are warming? In the longer term, the biogeography of Antarctic lakes will continue to be dynamic. New species will arrive, others will become extinct. The biogeographic zones long-proposed may continue to hold, though more precise knowledge of current distributions and responses to climate change may refine our view.MICROMAT, LAQUA