Mutation rates and fitness consequences of mosaic chromosomal alterations in blood.

Mosaic chromosomal alterations (mCAs) are common in cancers and can arise decades before diagnosis. A quantitative understanding of the rate at which these events occur, and their functional consequences, could improve cancer risk prediction and our understanding of somatic evolution. Using mCA clone size estimates from the blood of approximately 500,000 UK Biobank participants, we estimate mutation rates and fitness consequences of acquired gain, loss and copy-neutral loss of heterozygosity events.

Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues.

Genetic alterations under positive selection in healthy tissues have implications for cancer risk. However, total levels of positive selection across the genome remain unknown. Passenger mutations are influenced by all driver mutations, regardless of type or location in the genome.

Systematic Profiling of Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor.

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A () are the most common driver of this state. variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated mutations, and found that 74% were loss-of-function mutations.

The evolutionary dynamics and fitness landscape of clonal hematopoiesis.

Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis).

Osmoregulation and branchial plasticity after acute freshwater transfer in red drum, Sciaenops ocellatus.

Red drum, Sciaenops ocellatus, is an estuarine-dependent fish species commonly found in the Gulf of Mexico and along the coast of the southeastern United States. This economically important species has demonstrated freshwater tolerance; however, the physiological mechanisms and costs related to freshwater exposure remain poorly understood. The current study therefore investigated the physiological response of red drum using an acute freshwater transfer protocol.