An analysis of decades-old data and long-frozen fish reveals the genomic basis of the animals' rapid evolutionary adaptation to humans in our current geological age. By assessing a years-old study that simulated intensive fishing on thousands of small Atlantic silversides over several generations, a team of researchers discovered evolutionary shifts in fish's overall growth rate. They then sequenced the genomes of frozen silversides used in the earlier study and tracked genomic changes that influenced body size, finding that the observed decline in body size was due to two polygenic mechanisms: the scientists uncovered parallel changes in hundreds of unlinked variants concentrated in growth-related genes, as well as the rapid rise of a supercluster of genes that dominated the evolutionary dynamic in one replicate line but not in others, they write. "Parallel phenotypic changes thus masked highly divergent genomic responses to selection, illustrating how contingent rapid adaptation can be in the face of strong human-induced selection."
A therapy based on stem cells modified using CRISPR genome-editing technology has shown promise for treating hemoglobin disorders in animal experiments, according to a study in Science Translational Medicine. A team of researchers from industry and academia used CRISPR to introduce into stem cells naturally occurring mutations that boost the production of fetal hemoglobin. The cells were then transplanted into a nonhuman primate autologous transplantation model, which took up the cells with as much as 30 percent engraftment after one year and stably reactivated fetal hemoglobin. By editing highly enriched stems cells, the scientists were able to cut the number of cells required for transplantation by 10-fold, considerably reducing the need for editing reagents. "The frequency of engrafted, gene-edited cells persisting in vivo using this approach may be sufficient to ameliorate the phenotype for a number of genetic diseases, they conclude.
A new genomic analysis appearing in Science this week provides insights into the spread of canine transmissible venereal tumor (CTVT), a sexually transmitted cancer lineage that arose in dogs thousands of years ago. The study's authors construct a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's expansion across the globe. Variations in mutational exposure reveal a "highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished," they write. The team also correlates ultraviolet light mutagenesis with tumor latitude and describe tumors with heritable hyperactivity of an endogenous mutational process. Lastly, they find that CTVT displays little evidence of ongoing positive selection, with negative selection detectable only in essential genes. GenomeWeb has more on this, here, as does the Scan, here.