Researchers in the Comparative Biology of Mitotic Division Laboratory have shown that the transfer of genes from bacteria into more complex organisms can give them an advantage but requires remodelling of the host’s biology. 

Cryo-EM imaging shows co-existing ordered (thick) and disordered (thin) areas in asymmetrical phospholipid-based model membranes containing either ergosterol (left) or a hopanoid diplopterol (right). The remarkably similar membrane thickness values show that, when paired up with asymmetrical phospholipids, sterols and hopanoids could substitute for each other in yeast membranes. 

Genes are usually passed down from our ancestors in a vertical line of descent. But genes can also be acquired horizontally, where they are transferred between unrelated organisms. Bacteria most commonly use this type of exchange, but genes can also be passed from simple bacteria to more complex multicellular organisms. 

In research published in Nature Communications, the lab explored the integration of a horizontally transferred gene coding for an enzyme called squalene-hopene cyclase (Shc1) from bacteria into a type of yeast called S. japonicus. 

Most eukaryotic organisms, including yeast, need oxygen to survive because several biochemical reactions require it. This includes the production of sterols (ergosterol in yeast and cholesterol in humans), which are needed for functioning cell membranes.  

S. japonicus can survive without oxygen, which is believed to be linked to the transferred Shc1 enzyme. This enzyme generates hopanoids, molecules that are functionally similar to sterols, in the absence of oxygen.

Transfer of evolutionary advantages 

Through a series of experiments, the team showed that S. japonicus can switch between using an enzyme that generates sterols in the presence of oxygen, called Erg1, and the horizontally acquired Shc1 enzyme to produce hopanoids in conditions without oxygen. 

The team then integrated Sch1 into a closely related yeast species, S. pombe, which can’t grow without oxygen and depends on sterols. When S. pombe had Sch1, some hopanoids were produced, but it still relied primarily on sterols. 

The team then reduced the production of Erg1 in S. pombe, and more hopanoids were produced, showing that the enzymes compete with each other for ingredients needed to make both sterols and hopanoids.

As S. japonicus can grow in higher temperatures, the scientists also tested if the addition of Sch1 would allow S. pombe to survive in higher temperatures. They found that S. pombe could now survive in higher temperatures and without oxygen, showing that the acquisition of the new gene immediately allowed it to adapt to different environments.

Making room for hopanoids 

S. pombe has classic cell membranes, formed of two layers of lipids with symmetrical fatty acid tails meeting in the middle, whereas the bulk of S. japonicus membrane lipids have asymmetrical fatty acid tails. Using cryo-electron microscopy, the team could see that membranes made from the S. japonicus-like lipids were much thinner than others. 

They found that hopanoids are best accommodated in the membrane if it is made of asymmetrical lipids, so S. japonicus has adapted to produce two different lengths of fatty acids. This allows the membrane to have more flexibility and explains why some proteins in S. japonicus evolved shorter transmembrane domains to match the decreased membrane width. 

They concluded that taking in the gene from bacteria provided S. japonicus with an advantage against other yeast species, especially in high temperature and low oxygen environments. However, it had to alter its cell membrane to accept hopanoids.

Snezhka Oliferenko, Group Leader of the Comparative Biology of Mitotic Division Laboratory, said:

“When we think about genes transferring between species, we think about how the gene’s function might change in a new organism. But we don’t always consider how the organism has to adapt to allow the new gene to work. 

“We’ve shown here that it’s a two-way street: taking in a gene might confer an evolutionary advantage, allowing a species like yeast to thrive in specific environments, but it also puts pressure on the host to evolve. It’s a trade-off between having benefits over your competitors and the cost of changing your biology.”

The research was led by co-first authors Bhagyashree Rao and Elisa Gomez-Gil, both postdocs in Snezhka's lab. The team also worked with Qu Chen and Peter Rosenthal in the Structural Biology of Cells and Viruses Laboratory, and Vanessa Nunes and James Macrae in the Metabolomics STP. 

This research was a collaboration between the Crick, King’s College London and the Hungarian Academy of Sciences.