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Widely considered an anthropogenic phenomenon, antimicrobial resistance (AMR) is a naturally occurring mechanism that microorganisms use to gain competitive advantage. AMR represents a significant threat to public health and has generated criticism towards the overuse of antimicrobial drugs. Livestock have been proposed as important reservoirs for AMR accumulation. Here, we show that assemblages of AMR genes in cattle and ungulates from natural environments (Yellowstone and Rocky Mountain National Parks) are all dominated by genes conferring resistance to tetracyclines. However, cattle feces contained higher proportions of erm(A-X) genes conferring resistance to macrolide antibiotics. Medically important AMR genes differed between cattle and natural ungulates, but cumulatively were more predominant in natural soils. Our findings suggest that the commonly described predominance of tetracycline resistance in cattle feces is a natural phenomenon among multiple ungulate species and not solely a result of antimicrobial drug exposure. Yet, the virtual absence of macrolide resistance genes in natural ungulates suggests that macrolide usage in agriculture may enrich these genes in cattle. Our results show that antimicrobial use in agriculture may be promoting a potential reservoir for specific types of AMR (i.e., macrolide resistance) but that a significant proportion of the ungulate resistome appears to have natural origins.

Contains fulltext : 139109.pdf (Publisher’s version ) (Open Access) Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.