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This Week in Science: Feb 20, 2015

A team from Brandeis University reports in Science this week on the discovery of a handful of ancient genetic mutations that are responsible for the activity of the cancer drug Gleevec against tumors expressing one type of oncogene, but not a related one. Gleevec works by blocking the activity of Abl tyrosine kinase, but is ineffective against closely homologous tyrosine kinases such as Src. To find out why, the researchers reconstructed the sequence of the evolutionary ancestor of both enzymes and created a replica of the protein to test with Gleevec. In doing so, they identified mutations that changed the conformation of the enzyme, altering its binding energy and creating greater affinity for the drug on the Abl evolutionary pathway and less on the Src pathway.

Also in Science, researchers from Columbia University and their collaborators present the results of a whole-exome sequencing study of more than 2,800 amyotrophic lateral sclerosis (ALS) patients, which revealed a new gene related to the progressive neurological disease. Called TBK1, the gene is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including two previously linked to ALS. The findings point to potentially new therapeutic targets for treating the disease, the researchers say.


The Scan

Foxtail Millet Pangenome, Graph-Based Reference Genome

Researchers in Nature Genetics described their generation of a foxtail millet pangenome, which they say can help in crop trait improvement.

Protein Length Distribution Consistent Across Species

An analysis in Genome Biology compares the lengths of proteins across more than 2,300 species, finding similar length distributions.

Novel Genetic Loci Linked to Insulin Resistance in New Study

A team reports in Nature Genetics that it used glucose challenge test data to home in on candidate genes involved in GLUT4 expression or trafficking.

RNA Editing in Octopuses Seems to Help Acclimation to Shifts in Water Temperature

A paper in Cell reports that octopuses use RNA editing to help them adjust to different water temperatures.