De NovoEmergence of Peptides That Confer Antibiotic Resistance

De novogene origination from nonfunctional DNA sequences was long assumed to be implausible. However, recent studies have shown that large fractions of genomic noncoding DNA are transcribed and translated, potentially generating new genes. Experimental validation of this process so far has been limited to comparative genomics, in vitroselections, or partial randomizations. Here, we describe selection of novel peptides in vivousing fully random synthetic expression libraries. The peptides confer aminoglycoside resistance by inserting into the bacterial membrane and thereby partly reducing membrane potential and decreasing drug uptake. Our results show that beneficial peptides can be selected from random sequence pools in vivoand support the idea that expression of noncoding sequences could spark the origination of new genes.