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This Week in PNAS: Dec 19, 2012

In the early, online edition of the Proceedings of the National Academy of Science, the University of Maryland's Christopher Plowe leads an international team exploring the genetics of drug resistance in Plasmodium falciparum malaria parasites from Southeast Asia. With SNP genotype data for parasites from hundreds of patient blood samples collected in Cambodia, Bangladesh, and Thailand, the researchers used signs of recent selection to track down four variants linked to slower-than-usual parasite clearance after artemesinin treatment. Of these, two SNPs fell in a region of the P. falciparum genome showing signs of particularly pronounced positive selection in pathogens from western Cambodia, where artemisinin-resistance recently emerged.

Alleles associated with resistance to pyrethroid insecticides in the malaria-carrying mosquito Anopheles funestus are the subject of another PNAS online study. There, a team from the Liverpool School of Tropical Medicine's Vector Biology Department used custom microarrays to profile expression patterns from An. funestus mosquitoes in Malawi and Mozambique, uncovering a pair of tandemly duplicated cytochrome P450 genes — CYP6P9a and CYP6P9b — with elevated expression in pyrethroid-resistant mosquitoes. "Variability analysis identified that a single allele of each of these genes is predominantly associated with pyrethroid resistance in field populations from both counties," senior author Charles Wondji and colleagues write, "which is suggestive of a single origin that has since spread across the region."

Finally, researchers from France and the US explore bacterial mutation rate dynamics. The team resequenced the genomes of 22 Escherichia coli clones from a dozen populations grown under defined conditions over tens of thousands of generations, including a population known to have developed a hyper-mutation phenotype during this process. Phylogenetic relationships between the clones suggest that a mutation rate-lowering alteration was introduced into two E. coli lineages after the hyper-mutation change, highlighting the balance between mutation-related mechanisms that reduce genetic load and those that spur adaptive evolution.

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.