Maize HapMap2 identifies extant variation from a genome in flux

Whereas breeders have exploited diversity in maize for yield improvements, there has been limited progress in using beneficial alleles in undomesticated varieties. Characterizing standing variation in this complex genome has been challenging, with only a small fraction of it described to date. Using a population genetics scoring model, we identified 55 million SNPs in 103 lines across pre-domestication and domesticated Zea mays varieties, including a representative from the sister genus Tripsacum. We find that structural variations are pervasive in the Z. mays genome and are enriched at loci associated with important traits. By investigating the drivers of genome size variation, we find that the larger Tripsacum genome can be explained by transposable element abundance rather than an allopolyploid origin. In contrast, intraspecies genome size variation seems to be controlled by chromosomal knob content. There is tremendous overlap in key gene content in maize and Tripsacum, suggesting that adaptations from Tripsacum (for example, perennialism and frost and drought tolerance) can likely be integrated into maize.     

Mechanochemical analysis of DNA gyrase using rotor bead tracking

DNA gyrase is a molecular machine that uses the energy of ATP hydrolysis to introduce essential negative supercoils into DNA. The directionality of supercoiling is ensured by chiral wrapping of the DNA around a specialized domain of the enzyme before strand passage. Here we observe the activity of gyrase in real time by tracking the rotation of a submicrometre bead attached to the side of a stretched DNA molecule. In the presence of gyrase and ATP, we observe bursts of rotation corresponding to the processive, stepwise introduction of negative supercoils in strict multiples of two. Changes in DNA tension have no detectable effect on supercoiling velocity, but the enzyme becomes markedly less processive as tension is increased over a range of only a few tenths of piconewtons. This behaviour is quantitatively explained by a simple mechanochemical model in which processivity depends on a kinetic competition between dissociation and rapid, tension-sensitive DNA wrapping. In a high-resolution variant of our assay, we directly detect rotational pauses corresponding to two kinetic substeps: an ATP-independent step at the end of the reaction cycle, and an ATP-binding step in the middle of the cycle, subsequent to DNA wrapping.     

Molecular dynamics of cyclically contracting insect flight muscle in vivo

Flight in insects--which constitute the largest group of species in the animal kingdom--is powered by specialized muscles located within the thorax. In most insects each contraction is triggered not by a motor neuron spike but by mechanical stretch imposed by antagonistic muscles. Whereas 'stretch activation' and its reciprocal phenomenon 'shortening deactivation' are observed to varying extents in all striated muscles, both are particularly prominent in the indirect flight muscles of insects. Here we show changes in thick-filament structure and actin-myosin interactions in living, flying Drosophila with the use of synchrotron small-angle X-ray diffraction. To elicit stable flight behaviour and permit the capture of images at specific phases within the 5-ms wingbeat cycle, we tethered flies within a visual flight simulator. We recorded images of 340 micros duration every 625 micros to create an eight-frame diffraction movie, with each frame reflecting the instantaneous structure of the contractile apparatus. These time-resolved measurements of molecular-level structure provide new insight into the unique ability of insect flight muscle to generate elevated power at high frequency.     

Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR

Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors. Acquisition of drug resistance is linked to a specific secondary somatic mutation, EGFR T790M. Here we describe a family with multiple cases of non-small cell lung cancer associated with germline transmission of this mutation. Four of six tumors analyzed showed a secondary somatic activating EGFR mutation, arising in cis with the germline EGFR mutation T790M. These observations implicate altered EGFR signaling in genetic susceptibility to lung cancer.     

An H-2-associated difference in murine serum cholesterol levels

Summary We describe, in mice, a difference in serum cholesterol and adrenal weight associated with an H-2^a/H-2^b haplotype difference.