Copying Foreign Genes Helps Bacteria Withstand the Test of Time

Consider the following dilemma: You turn up for an exam, having no prior knowledge of the subject. You are handed one of two opportunities: You can get your answers either from an expert, but in a completely different language from yours or, alternatively, from someone who has only passable knowledge, but shares your language. Which would you choose?

Bacteria were put to a similar test in the lab of Prof. Yitzhak Pilpel of the Weizmann Institute of Science’s Molecular Genetics Department. He, Dr.OrnaDahan and other members of his lab team asked: When bacteria take on foreign genes, how does this affect their chances of survival, and do the bacteria prefer to take these genes from species that “speak” their language?

Bacteria reproduce asexually; mixing their genes with others – as happens in sexual reproduction – is a relatively new notion. In fact, as scientists discovered several decades ago, bacteria have evolved a method of “mixing and matching” genes in a process called horizontal gene transfer. Unlike the sexual, or vertical, gene transfer, in which genes are reshuffled and passed down from parents to offspring, in horizontal gene transfer, DNA gets mixed between unrelated individuals, including those of different species. “This is somewhat analogous to how languages evolve by occasionally acquiring foreign words, in the way that related Arabic and unrelated English terms have crept into the Hebrew vernacular,” says Pilpel.

Studying horizontal gene transfer in action is challenging, though. Scientists might first try to identify genes that do not look native to an organism’s genetic makeup – a bit like trying to spot a foreign-derived word among tens of thousands of entries in a dictionary. Some stand out, but others do not, and their “etymology” – the source of the foreign gene – is not always evident. Classical research methods could only provide scientists with a “snapshot” of the situation. To understand such transfers in an evolutionary context, scientists needed something more dynamic.

In Pilpel’s group, lab evolution is a research method, involving growing organisms in a test tube in a controlled environment and providing a sort of “movie” of the changes they undergo. “We took this research method one step further and introduced a unique element – foreign DNA from other species – allowing us, for the first time, to study horizontal gene transfer and its effects in real time,” says Dr.OrnaDahan, who led the study together with MSc students Shai Slomka De Oliveira and Itamar Françoise.

The scientists took a common bacterial species, Bacillus subtilis, and challenged them with a test: to survive in an uncomfortably salty solution. To help the bacteria pass the test, the researchers introduced foreign DNA from various microbial sources. Two such samples of DNA were taken from archaea in the Dead Sea, others from bacteria that live in the Mediterranean Sea. These species are completely unrelated to B. subtilis, but they are experts at thriving in high salinity. Yet another source of DNA was a close relative of B. subtilis; these were “novices” at living in a high-salt environment, having only recently “learned” how to do so through lab evolution.

By sequencing the genomes of the evolving populations over more than 500 generations, the scientists were able to identify when and how gene transfer took place. In one particularly surprising case, a large chunk – up to 2 percent – of the bacteria’s genome was replaced. This DNA was incorporated from the closely related organisms rather than from the unrelated, high-salinity experts, whose genome was apparently too “foreign and illegible” for the bacteria. Even so, the evolved generations “passed” the challenge: They were better able to better cope with high salt concentrations than their control counterparts.

Is gene transfer preferable to the tried-and-true process of mutation and adaptation in confronting new evolutionary challenges? Says Pilpel: “Horizontal gene transfer is a very costly process for an organism, especially as it involves the risk of incorporating genes that could be deleterious. So the fact that some of the foreign insertions ‘survived’ independently in several repetitions of the same experiment implies that they do indeed confer an adaptive advantage. Since mutations happen sequentially while, as we noted, more than one gene can be added through horizontal transfer, it might, in some cases, provide a shortcut to evolution.”

The findings of this study shed new light on gene sharing in organisms like bacteria that reproduce asexually. It may also illuminate the process of antibiotic resistance, which mainly evolves and spreads by gene transfer. If scientists can better understand how bacteria decide to adopt foreign genes, they might be able to slow or stop the process in the detrimental ones. The biotechnology industry could also use the gene transfer principle demonstrated in the experiments to evolve new strains of bacteria for various applications, including the degradation of plastics or other such environmental technologies.

Prof. Yitzhak Pilpel’s research is supported by the Helen and Martin Kimmel Award for Innovative Investigation. He is Head of the BraginskyCenter for the Interface between Science and the Humanities; Head of the Azrieli Institute for Systems Biology; Head of the Leo and Julia ForchheimerCenter for Molecular Genetics; and Head of the Kahn Family Research Center for Systems Biology of the Human Cell. His research is also supported by the Sharon Zuckerman Laboratory for Research in Systems Biology; the estate of Emile Mimran; and the European Research Council. Prof. Pilpel is the incumbent of the Ben May Professorial Chair.