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This Week in Cell: Oct 17, 2018

Researchers from France, Belgium, Italy, and Qatar explore metastatic tumor evolution and clonal dynamics in response to selection by the immune microenvironment. The team used exome sequencing to assess somatic mutation and copy number patterns in dozens of matched normal, primary, and metastatic samples collected over more than a decade in two individuals with stage IV colorectal cancer, while characterizing tumor-infiltrating lymphocytes with immunohistochemistry. Based on the alterations detected in recurring tumors that did or did not dodge immunoediting, the authors suggest that metastasis may progress via "a parallel selection model … where branched evolution could be traced back to immune-escaping clones."

With a parallel, CRISPR-Cas9-based genome editing approach called CRISPEY, a Stanford University team systematically introduced more than 16,000 genetic variants into the budding yeast model organism Saccharomyces cerevisiae, following the functional and fitness consequences of these edits. In the process, the researchers identified 572 variants influencing the fitness of yeast growing in glucose. Many of those fell in promoter sequences, they note, while fewer than one-fifth affected sequences in a manner that changed the resulting amino acids. "We observed that yeast genetically encoded fitness differences are mainly cis-regulatory and often involve multiple tightly clustered causal variants per locus," they write, "affecting fitness in the same direction."

Finally, University of Arizona and Stanford University researchers describe an apparent role for RNA viruses in fueling adaptive introgression of Neanderthal DNA into modern human genomes. The team focused on more than 4,500 virus-interacting proteins, demonstrating that stretches of Neanderthal sequences coding for RNA virus-interacting proteins were particularly prone to being adaptive in individuals from European populations. The authors note that "even though we focused on Neanderthal ancestry, we anticipate that it should also be possible to study the impact of ancient epidemics on introgression from Denisovans to modern humans, especially in populations such as Melanesians with a larger percentage of Denisovan ancestry."