PNAS Papers on MERS-CoV in Africa, Ancient Goat Domestication, Cell Cycle Checkpoint
A University of Hong Kong-led team looks at features found in Middle East respiratory syndrome coronaviruses (MERS-CoV) in Africa to understand why zoonotic forms of the virus have centered in the Arabian Peninsula so far, despite the presence of MERS-CoV-carrying dromedary camels on the African continent. Using a combination of genome sequences, phylogenetics, and phenotypic clues, the researchers saw hints that the clade C MERS-CoVs turning up in East Africa or West Africa have reduced replication competence and less infectious spike protein sequences compared to the more pathogenic coronavirus clades detected in the Arabian Peninsula — results they explored further in mouse models of human lung tissues. "The findings suggest that MERS-CoV now entrenched in the Arabian Peninsula has acquired increased pathogenic potential for humans," they report, pointing to the potential threat of introducing pathogenic clade B MERS-CoVs to Africa, where they may outcompete existing forms of the virus.
Researchers from Trinity College Dublin, the University of Tehran, and elsewhere present evidence for goat domestication and its genomic consequences, going back thousands of years in Iran. By sequencing and analyzing 14 ancient goat genomes, along with nearly three dozen mitochondrial DNA genomes, from archeological sites in on western Iran's Zagros Mountains, the team saw distinct genetic features that appeared to distinguish domestic goat-related animals from their wild counterparts, as well as other genomic features such as long runs of homozygosity that were consistent with animal management by humans. "These genomes show two distinct clusters: those with domestic affinity and a minority group with stronger wild affinity, indicating that managed goats were genetically distinct from wild goats at this early horizon," the authors note, adding that these and other findings from the study "support management of genetically domestic goat by circa 8200 cal BC, and represent the oldest to-this-date reported livestock genomes."
Another study slated to appear in PNAS this week provides clues to an "intra-S phase" cell cycle checkpoint that deals with delayed replisome activity when replication stress arises. Investigators in China and the UK used deep genomic DNA sequencing, viability assays, and other approaches to characterize the replication elongation checkpoint in eukaryotic and fission yeast cells, teasing out the kinase enzyme activity and other events that delay replication elongation and activity by a replicative helicase containing Cdc45, MCM, and Cds1 (CMG) in response to replication fork stalling. "This study demonstrates that the intra-S phase checkpoint directly regulates replication elongation, reduces CMG helicase processivity, prevents CMG helicase delinking from DNA polymerases, and therefore helps preserve the integrity of stalled replisomes and replication forks," they report.
Courtesy of Genomeweb