Dynamics of lineage diversity during adaptation to weak antibiotic pressure

Tracking low-frequency lineages in large microbial populations is key to fully elucidating their evolutionary dynamics, especially under weak selection pressures and short time scales. However, resolution is often limited by methods for labeling lineages or whole-genome sequencing. To overcome this challenge, we introduce a large library of random DNA barcodes into E. coli, allowing us to track lineages down to tens or hundreds of cells. We observe two distinct phases of lineage dynamics during adaptation to low levels of antibiotics. During the first phase, the diversity of lineages undergoes a rapid and predictable drop which is characteristic of the drug and concentration. In particular, we find that low amounts of trimethoprim actually slow down the loss of diversity compared to the absence of drug. This initial loss of diversity appears to be driven by selection on standing genetic variation, leading to groups of lineages rising or falling together both within and between populations. During the second phase of dynamics, new mutations arise on these lineages, leading to clonal interference. Lineage diversity then stabilizes at a low but nonzero level, which appears to be universal across conditions despite the variation in initial dynamics.