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Volume 489 Issue 7417

Editorials

News

News Features

News & Views

EvolutionHow the unicorn got its horn p.504

An experiment studying bacterial populations over thousands of generations shows that a novel trait can evolve through rearrangement and amplification of a few pre-existing genes. See Article p.513

doi: 10.1038/nature11487

Quantum computationSpinning towards scalable circuits p.505

Silicon devices form the backbone of modern computers. It turns out that they might also be a natural hardware platform for a new era of computing technology that uses the principles of quantum physics. See Letter p.541

doi: 10.1038/nature11488

Network scienceLuck or reason p.507

The concept of preferential attachment is behind the hubs and power laws seen in many networks. New results fuel an old debate about its origin, and beg the question of whether it is based on randomness or optimization. See Letter p.537

doi: 10.1038/nature11486

Regenerative biologySkin, heal thyself p.508

Simply grabbing an African spiny mouse can cause it to lose up to 60% of the skin on its back. Analysis of the mouse's astounding shedding and healing capacity provides insight into the biomechanics of tissue regeneration. See Letter p.561

doi: 10.1038/489508a

Electronics'Cut and stick' ion gels p.510

Ion gels are composites of ionic liquids and polymers. Free-standing forms of ion gels have now been made that can be neatly cut with a razor blade and stuck onto semiconductor materials to make transistors.

doi: 10.1038/489510a

Cancer metabolismWhen more is less p.511

A tightly regulated enzyme balances energy production and the synthesis of macromolecules from glucose in cancer cells. Upsetting this balance by stimulating the enzyme's activity can suppress tumour growth in mice.

doi: 10.1038/489511a

Articles

Genomic analysis of a key innovation in an experimental Escherichia coli population p.513

Evolutionary novelties have been important in the history of life, but their origins are usually difficult to examine in detail. We previously described the evolution of a novel trait, aerobic citrate utilization (Cit+), in an experimental population of Escherichia coli. Here we analyse genome sequences to investigate the history and genetic basis of this trait. At least three distinct clades coexisted for more than 10,000 generations before its emergence. The Cit+ trait originated in one clade by a tandem duplication that captured an aerobically expressed promoter for the expression of a previously silent citrate transporter. The clades varied in their propensity to evolve this novel trait, although genotypes able to do so existed in all three clades, implying that multiple potentiating mutations arose during the population’s history. Our findings illustrate the importance of promoter capture and altered gene regulation in mediating the exaptation events that often underlie evolutionary innovations.

doi: 10.1038/nature11514

Comprehensive genomic characterization of squamous cell lung cancers p.519

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

doi: 10.1038/nature11404

Cross-neutralization of influenza A viruses mediated by a single antibody loop p.526

Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.

doi: 10.1038/nature11414

Letters