Abstract. An exchange with genetic information is one of the key factors driving bacterial evolution. However, the mechanisms for integration of horizontally transferred genes into the regulatory network of a new host remain almost unexplored so far. The present work aimed to investigate this adaptive process, specifically, involvement of the transcription machinery of bacterial cells.  Two foreign genes in the genome of  Escherichia coli K12 MG1655 were substituted with their copies from the genomes of predicted donors, and a long-term evolution experiment was initiated for both mutant and control cultures. After 2000 (for the sfmA gene) and 4000 (for the ydhZ gene) generations, modified and native genomic regions were amplified and used for population sequencing. Spontaneous mutations were analyzed, and it was found that substitutions of G/C- to A/T-pairs occurred more frequently in the modified regions as compared to non-modified, whereas A/T → G/C substitutions occurred more rarely.   That means that the host genome responds to integration of foreign genetic material with an adaptive reaction aimed to enrich the modified region with A/T-pairs. In the course of long-term evolution, it may result either in “silencing” of an unfavourable gene with a specific suppressor of foreign genes,  H-NS, or in creation of a promoter acceptable for adequate expression as a part of promoter island.