image: During the replication of the bacterial chromosome, genes close to the replication start point (red) exist in multiple copies, while genes close to the endpoint do not (blue). At faster growth, this effect becomes stronger, such that genes close to the start point can be read from up to 8 gene copies simultaneously, leading to higher expression levels. Depending on how the demand for the expression of a specific gene changes with growth rate, natural selection drives it to an appropriate positioning along the chromosome to exploit this gene dosage effect. (Fig.: HHU / Xiao-Pan Hu)
Credit: HHU / Xiao-Pan Hu
Bioinformaticians from Heinrich Heine University Düsseldorf (HHU) and the university in Linköping (Sweden) have established that the genes in bacterial genomes are arranged in a meaningful order. In the renowned scientific journal Science, they describe that the genes are arranged by function: If they become increasingly important at faster growth, they are located near the origin of DNA replication. Accordingly, their position influences how their activity changes with the growth rate.
Are genes distributed randomly along the bacterial chromosome, as if scattered from a salt shaker? This opinion, which is held by a majority of researchers, has now been disputed by a team of bioinformaticians led by Professor Dr Martin Lercher, head of the research group for Computational Cell Biology at HHU.
When bacteria replicate their genetic material in preparation for cell division, the process starts at a specific point on the bacterial chromosome and continues along the chromosome in both directions.
Dr Xiao-Pan Hu from HHU, lead author of the study now published in Science: “For a short time during this process, there are more copies of those genes located closer to the origin of replication than of those located further away. Accordingly, genes close to the origin can be read more frequently.”
“We have established that these genes are particularly important for cell growth – e.g. those whose products assemble the proteins of the bacteria,” adds Professor Lercher, corresponding author of the study. By contrast, genes rarely needed in the growth phases are usually found at the opposing end of the chromosome, where they are duplicated late in the process.
The researchers used bioinformatic and mathematical methods to analyse the positions of more than 4,400 gene families in over 900 different bacterial species. They found that the positioning of the genes along the chromosome must have arisen as a consequence of evolutionary pressure, as those bacteria that can grow particularly quickly as a result of optimally placed genes have an evolutionary advantage.
Dr Hu: “We now understand better how bacteria control their genes. The results really surprised us. They provide an excellent explanation of an important aspect of bacterial evolution: The right genomic positioning gave the bacteria existing today an advantage over their rivals.”
Lercher on further potential applications: “This understanding can also help design more efficient synthetic bacteria, e.g. for biotechnological or medical applications.”
Original publication
Xiao-Pan Hu, Bayu Brahmantio, Krzysztof Bartoszek, Martin J. Lercher. Most bacterial gene families are biased toward specific chromosomal positions. Science 388/6743 (2025).
Journal
Science
Article Title
Most bacterial gene families are biased toward specific chromosomal positions
Article Publication Date
11-Apr-2025