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This Week in PNAS: Aug 28, 2018

In the early, online edition of the Proceedings of the National Academy of Sciences, researchers at Brown University and the Broad Institute follow microevolution in the opportunistic yeast pathogen Candida albicans. Using deep whole-genome sequencing, the team tracked the mutations that arose in four different C. albicans clinical isolates over time after growth in lab cultures or in infected mouse models. In addition to tallying mutation rates across the genome in these conditions, the investigators found that the microevolution events tended to involve de novo substitutions, short-track recombination events, and loss-of-heterozygosity events, while chromosomal changes occurred relatively infrequently. "Together, these data provide a high-resolution picture of how the heterozygous diploid genome of a fungal pathogen undergoes evolution over short time scales," they report.

A Stanford University-led team describes apparent ties between shorter-than-usual telomere repeats at the end of chromosomes and genetic cardiomyopathies — particularly end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Although cardiomyocyte cells typically maintain more stable telomeres than other cell types as individuals age, the researchers explain, their quantitative FISH experiments suggest that telomeres are significantly shorter in cardiomyocyte cells from individuals with HCM or DCM, who carry characteristic mutations in genes such as TNNI3, MYBPC3, MYH7, DMD, TNNT2, or TTN. Similar patterns turned up when they used additional assays to assess telomere length in cardiomyocyte cells produced from induced pluripotent stem cells derived from individuals with DCM or HCM.

University of Pittsburgh researchers characterize circular RNAs produced by Epstein-Barr virus (EBV) and Kaposi's sarcoma herpes virus (KSHV) — gammaherpesviruses known for contributing to some human cancer and to lymphoproliferative conditions such as post-transplant lymphoproliferative disease (PTLD). In an effort to find new viruses involved in PTLD, the team used RNA sequencing to profile EBV-negative and -positive PTLD samples, identifying circRNAs expressed from a so-called "BamHI A rightward transcript" (BART) locus. These circBARTs were subsequently found in EBV- or KSHV-positive samples from conditions ranging from PTLD to lymphoma. From these and other results, the authors noted that such circRNAs "can be long-lived, unique tumor biomarkers that may also open new research opportunities into understanding how these viruses cause cancer."