Compared to their eukaryotic counterparts, bacterial genomes are small and contain extremely tightly packed genes. Therefore, discovering a large number of short repetitive sequences in the genomes of Pseudomonads and Enterobacteria is unexpected. These sequences can independently replicate in the host genome and form populations that persist for millions of years. Here we model the interactions of intragenomic sequence populations with the bacterial host. In a simple model, sequence populations either expand until they drive the host to extinction or the sequence population gets purged from the genome. Including horizontal gene transfer does not change the qualitative outcome of the model and leads to the extinction of the sequence population.However, a sequence population can be stably maintained, if each sequence provides a benefit that decreases with increasing sequence population size. But concurrently, the replication of the sequence population needs to be costly to the host. Surprisingly, in regimes where horizontal gene transfer plays a role, the benefit conferred by the sequence population does not have to exceed the damage it causes. Together, our analyses provide a plausible scenario for the persistence of sequence populations in bacterial genomes. More importantly, we hypothesize a limited biologically relevant parameter range, which can be tested in future experiments. * These authors contributed equally to this work; hyejin.park@apctp.org † These authors contributed equally to this work ‡ bertels@evolbio.mpg.de 1 Repetitive sequences can be found in most genomes. They are particularly abundant in eukaryotes, where often only a small proportion of the genome encodes for host proteins [1]. In contrast, about 90% of a typical bacterial genome encodes for host proteins [2].The extragenic space is mostly taken up by rRNA, tRNA, transcription and translation promoters, repressors and terminators [3]. Yet, repetitive sequences can be found in the extragenic space of many bacteria [4].Repetitive sequences were first identified in Escherichia coli in the early 1980s [5]. Then, due to their sequence characteristics, they were called REP sequences, short for repetitive extragenic palindromic sequences [6]. However, it was unclear if REP sequences fulfil a functional role in the host bacterium and if so what kind of function this might be. Numerous studies found REP sequences to be involved in different biological processes, for example in transcription termination, RNA stabilisation, gyrase and integration host factor binding, as well as nucleoid folding [5,[7][8][9][10][11]. However, whether the identified functions are locally co-opted, or common to all REP sequences and therefore able to explaining the presence of REP sequences in the bacterial genome, is not clear.To determine whether a function is incidental or whether it can explain the persistence and emergence of an entire sequence class requires the understanding of the evolution of REP sequences. A study in Pseudomonas fluorescens SBW25 showed that R...