Genetics: relatedness among east African coelacanths

Coelacanths were discovered in the Comoros archipelago to the northwest of Madagascar in 1952. Since then, these rare, ancient fish have been found to the south off Mozambique, Madagascar and South Africa, and to the north off Kenya and Tanzania -- but it was unclear whether these are separate populations or even subspecies. Here we show that the genetic variation between individuals from these different locations is unexpectedly low. Combined with earlier results from submersible and oceanographic observations, our findings indicate that a separate African metapopulation is unlikely to have existed and that locations distant from the Comoros were probably inhabited relatively recently by either dead-end drifters or founders that originated in the Comoros.     

Initial sequencing and comparative analysis of the mouse genome

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.     

Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4+ T-cells

This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG₁ simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG₁ was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG₁ short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG₁ before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG₁ anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).     

Linking mantle plumes, large igneous provinces and environmental catastrophes

Large igneous provinces (LIPs) are known for their rapid production of enormous volumes of magma (up to several million cubic kilometres in less than a million years), for marked thinning of the lithosphere, often ending with a continental break-up, and for their links to global environmental catastrophes. Despite the importance of LIPs, controversy surrounds even the basic idea that they form through melting in the heads of thermal mantle plumes. The Permo-Triassic Siberian Traps--the type example and the largest continental LIP--is located on thick cratonic lithosphere and was synchronous with the largest known mass-extinction event. However, there is no evidence of pre-magmatic uplift or of a large lithospheric stretching, as predicted above a plume head. Moreover, estimates of magmatic CO(2) degassing from the Siberian Traps are considered insufficient to trigger climatic crises, leading to the hypothesis that the release of thermogenic gases from the sediment pile caused the mass extinction. Here we present petrological evidence for a large amount (15?wt%) of dense recycled oceanic crust in the head of the plume and develop a thermomechanical model that predicts no pre-magmatic uplift and requires no lithospheric extension. The model implies extensive plume melting and heterogeneous erosion of the thick cratonic lithosphere over the course of a few hundred thousand years. The model suggests that massive degassing of CO(2) and HCl, mostly from the recycled crust in the plume head, could alone trigger a mass extinction and predicts it happening before the main volcanic phase, in agreement with stratigraphic and geochronological data for the Siberian Traps and other LIPs.     

Ancestral polyploidy in seed plants and angiosperms

Whole-genome duplication (WGD), or polyploidy, followed by gene loss and diploidization has long been recognized as an important evolutionary force in animals, fungi and other organisms, especially plants. The success of angiosperms has been attributed, in part, to innovations associated with gene or whole-genome duplications, but evidence for proposed ancient genome duplications pre-dating the divergence of monocots and eudicots remains equivocal in analyses of conserved gene order. Here we use comprehensive phylogenomic analyses of sequenced plant genomes and more than 12.6 million new expressed-sequence-tag sequences from phylogenetically pivotal lineages to elucidate two groups of ancient gene duplications-one in the common ancestor of extant seed plants and the other in the common ancestor of extant angiosperms. Gene duplication events were intensely concentrated around 319 and 192 million years ago, implicating two WGDs in ancestral lineages shortly before the diversification of extant seed plants and extant angiosperms, respectively. Significantly, these ancestral WGDs resulted in the diversification of regulatory genes important to seed and flower development, suggesting that they were involved in major innovations that ultimately contributed to the rise and eventual dominance of seed plants and angiosperms.