Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility

The epidermal growth factor receptor (EGFR) is a member of the ErbB family that can promote the migration and proliferation of breast cancer cells. Therapies that target EGFR can promote the dimerization of EGFR with other ErbB receptors, which is associated with the development of drug resistance. Understanding how interactions among ErbB receptors alter EGFR biology could provide avenues for improving cancer therapy. We found that EGFR interacted directly with the CYT1 and CYT2 variants of ErbB4 and the membrane-anchored intracellular domain (mICD). The CYT2 variant, but not the CYT1 variant, protected EGFR from ligand-induced degradation by competing with EGFR for binding to a complex containing the E3 ubiquitin ligase c-Cbl and the adaptor Grb2. Cultured breast cancer cells overexpressing both EGFR and ErbB4 CYT2 mICD exhibited increased migration. With molecular modeling, we identified residues involved in stabilizing the EGFR dimer. Mutation of these residues in the dimer interface destabilized the complex in cells and abrogated growth factor-stimulated cell migration. An exon array analysis of 155 breast tumors revealed that the relative mRNA abundance of the ErbB4 CYT2 variant was increased in ER+ HER2- breast cancer patients, suggesting that our findings could be clinically relevant. We propose a mechanism whereby competition for binding to c-Cbl in an ErbB signaling heterodimer promotes migration in response to a growth factor gradient

Genetic structure and different color morphotypes suggest the occurrence and bathymetric segregation of two incipient species of Sebastes off Argentina

Rockfishes of the genus Sebastes are extensively distributed in the Pacific and Atlantic oceans. Although the occurrence of two morphologically similar species in the Southern Hemisphere, Sebastes oculatus and Sebastes capensis, is now clearly established, the taxonomic status and phylogeographic patterns for the genus in the region have not yet been completely resolved. In this study, we provide new insights into the taxonomy and evolutionary relationships of rockfishes inhabiting the Southwestern Atlantic Ocean, off the coast of mainland Argentina, by combining mitochondrial DNA (mtDNA) control region sequences, microsatellite data and color pattern analyses. Differences in coloration (-dark- and -light- fish) together with bathymetric segregation between color morphotypes were evident from fish collection and literature review. In addition, the mtDNA phylogenetic analysis and Bayesian clustering analysis using microsatellite data separated the fish into two distinct groups (FST = 0.041), most likely representing incipient species. Our results suggest that speciation-by-depth in the absence of physical barriers could be a widespread mechanism of speciation in Sebastes from both the Northern and Southern Hemispheres. Nevertheless, the degree of genetic differentiation found, added to the large number of individuals displaying high levels of admixture, points to the occurrence of incomplete reproductive barriers between color morphotypes. Beyond the taxonomic and phylogeographic implications of our findings, the occurrence of distinct groups of Sebastes off the coast of Argentina being targeted by different fisheries (angling and trawling) have consequences for the design and implementation of appropriate fishery regulations to avoid overharvest of either group.Fil: Venerus, Leonardo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Ciancio Blanc, Javier Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Riva Rossi, Carla Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Gilbert Horvath, Elizabeth A.. National Marine Fisheries Service; Estados UnidosFil: Gosztonyi, Atila Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Garza, John Carlos. National Marine Fisheries Service; Estados Unido