Chromosomal inversions are important drivers of genome evolution. The Eurasian malaria vector Anopheles messeae has five polymorphic inversions. A cryptic species, An. daciae, has been discriminated from An. messeae based on five fixed nucleotide substitutions in the internal transcribed spacer 2 (ITS2) of ribosomal DNA. However, the inversion polymorphism in An. daciae and the genome divergence between these species remain unexplored. In this study, we sequenced the ITS2 region and analyzed the inversion frequencies of 289 Anopheles larvae specimens collected from three locations in the Moscow region. Five individual genomes for each of the two species were sequenced. We determined that An. messeae and An. daciae differ from each other by the frequency of polymorphic inversions. Inversion X1 was fixed in An. messeae but polymorphic in An. daciae populations. The genome sequence comparison demonstrated genome-wide divergence between the species, especially pronounced on the inversion-rich X chromosome (mean Fst = 0.331). The frequency of polymorphic autosomal inversions was higher in An. messeae than in An. daciae. We conclude that the X chromosome inversions play an important role in the genomic differentiation between the species. Our study determined that An. messeae and An. daciae are closely related species with incomplete reproductive isolation.

Tetraploidy has long been of interest to both cell and cancer biologists, partly because of its documented role in tumorigenesis. A common model proposes that the extra centrosomes that are typically acquired during tetraploidization are responsible for driving tumorigenesis. However, tetraploid cells evolved in culture have been shown to lack extra centrosomes. This observation raises questions about how tetraploid cells evolve and more specifically about the mechanisms(s) underlying centrosome loss. Here, using a combination of fixed cell analysis, live cell imaging, and mathematical modeling, we show that populations of newly formed tetraploid cells rapidly evolve in vitro to retain a near-tetraploid chromosome number while losing the extra centrosomes gained at the time of tetraploidization. This appears to happen through a process of natural selection in which tetraploid cells that inherit a single centrosome during a bipolar division with asymmetric centrosome clustering are favored for long-term survival.

No abstract

Anaerobic arginine catabolism in Saccharomyces cerevisiae was genetically modified to allow assimilation of all four rather than just three of the nitrogen atoms in arginine. This was accomplished by bypassing normal formation of proline, an unusable nitrogen source in the absence of oxygen, and causing formation of glutamate instead. A pro3 ure2 strain expressing a PGK1 promoter-driven PUT2 allele encoding ⌬ 1 -pyrroline-5-carboxylate dehydrogenase lacking a mitochondrial targeting sequence produced significant cytoplasmic activity, accumulated twice as much intracellular glutamate, and produced twice as much cell mass as the parent when grown anaerobically on limiting arginine as sole nitrogen source.

Role of vascular endothelial growth factor in the response to vessel injury. In the post-embryonic life, physiological angiogenesis is tightly controlled. Angiogenesis also occurs in pathological circumstances such as tumor vessel proliferation, retinal neovascularization and ischemia. The development of collateral circulation is not only not deleterious, but life saving. Other cases such as neoplastic neovascularization are the basis of the continuous growth of tumors and metastases, and therefore constitute a target of therapeutical efforts. Among a list of molecules able to control angiogenesis, we emphasize the pivotal role of vascular endothelial growth factor (VEGF). VEGF is a potent mitogen for endothelial cells, but is devoid of mitogenic activity for other cell types. VEGF is a polypeptide with four main different isoforms that are remarkably different in terms of solubility and affinity for matrix proteins. VEGF interacts with two endothelial cell-specific tyrosine kinase receptors. The main interest of its study lies in VEGF's role in pathological angiogenic processes, where an increase in the VEGF mRNA expression has been consistently observed. An interesting example is the up-regulation of VEGF's and VEGF receptors' mRNA in a considerable number of human tumors and retina, where they have a critical role in the development of neovascularization. In recent work in our laboratory, we have found further potential interactions of VEGF with pathophysiological mechanisms, namely, the increase in VEGF gene expression under exposure to reactive oxygen species and the positive interaction between VEGF and erythropoietin. VEGF has outstanding possibilities for therapeutic applications aimed at inhibiting or favoring the development of new vessels.