Most cells share the same fundamental molecular machinery, but evolution has produced extraordinary diversity in form and function across species by subtly adjusting how that machinery behaves.
The cell membrane is a fundamental biological structure. These lipid layers surround and organise every cell, controlling everything from signalling to transport. But for membranes to function properly, their physicochemical properties must sit within a narrow range: for instance, not too rigid or too fluid.
Since environmental conditions such as variation in dietary lipids or fluctuating temperature may alter membrane fluidity, organisms must self-regulate. And different organisms have evolved different preferences for the properties of their cellular membranes.
For Snezhka Oliferenko, who leads the Crick’s Comparative Biology of Mitotic Division Lab, biological membranes are the perfect system for studying the evolution of cellular diversity across species. “By focussing on how cells build and regulate their membranes, we can uncover how diversity arises,” she explains.
“We want to understand how changes in lipid biochemistry affect cell makeup, cell behaviour and ultimately, cell evolution.”
In their latest study, published in Genes and Development, Snezhka and her team examined two closely related fission yeast species, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, which share a very similar genetic makeup, but are biologically very different.
A key factor in membrane fluidity is the level of ‘unsaturation’, which depends on the type of lipids present. Membranes with a higher proportion of unsaturated lipids that have cis-double bonds in their fatty acid tails, are more fluid because kinks in the tails prevent tight packing of lipids. S. pombe produces more flexible, fluid membranes, whereas S. japonicus membranes are more ordered and rigid. These differences provide a natural comparison for understanding how cells can evolve and maintain distinct physicochemical properties of their membranes.
Lead author Elisa Gomez-Gil, studied both species in detail, analysing the lipid composition of the membranes under different conditions and also the activity of the genes that control lipid production. “We focussed on a key feedback loop involving a protein called Mga2, which sits in the membrane and acts as a sensor,” describes Elisa. “When membranes become too rigid, Mga2 is activated. It is cleaved from the membrane and switches on a gene that produces Ole1, an enzyme that makes unsaturated fatty acids, restoring balance.”
Elisa compared how this system behaves in each yeast species, and then went a step further by editing parts of this feedback loop to test how each component behaved in a different biological context. “This allowed us to isolate which elements set the sensitivity of the system and understand how those elements have been tuned through evolution,” she adds.
They showed that each species has a different threshold for when the membrane needs adjusting, with S. pombe having a low tolerance for membrane rigidity, and that this was due to two key evolutionary shifts. Small differences in the part of the Mga2 protein that sits next to the membrane alter how readily it is cleaved when the membrane becomes too rigid. At the same time, changes in the Ole1 gene set the baseline level of the response, determining how much of the enzyme is produced once the system is activated.
When membranes become too rigid, Mga2 is activated. It is cleaved from the membrane and switches on a gene that produces Ole1, an enzyme that makes unsaturated fatty acids, restoring balance. Each yeast species has a different threshold for when the membrane needs adjusting.
This shows that the sensor and its downstream response have evolved together, ensuring the system still works even as the underlying membrane biochemistry shifts.
“We often think of evolution as creating new biological machinery,” adds Snezhka. “But in many cases, it’s fine tuning what’s already there. Much of the diversity we see across species may not come from entirely new genes or pathways, but from subtle shifts in how shared systems are regulated.”
