“We think complex cells evolved from the inside out, not theoutside in”

As a cell biologist working with yeast, flies and human cells, Buzz had long grown accustomed to staring at the elaborate internal structure ofeukaryotes but had never heard a convincing explanation for the origin of this dazzling complexity. Maybe the inside-out model could shed light on this, andon other puzzling features of modern eukaryotes too.

We started exchanging drawingsmade in snatched moments, on napkinsand loose sheets of paper, on buses, planes and trains. Looking at thesesketches, answers to some unexplained aspects of eukaryotic cell biology seemedto jump off the page: for instance, the model explained why the ER is directly linked to the bounding membrane of the nucleus, and why they both containchemicals similar to archaeal cell wall components.

Echoes of the past

The success of this way ofthinking got us wondering whether modern cells retain any echoes of their pastin the way they work. By thinking about the way cells grew and divided as theyevolved into modern eukaryotes, we were able to make some startling predictions for various aspects of cell biology that are currently poorly understood. Forinstance, the inside-out model suggests a role for the ER in determining thepattern of diffusion of molecules within cells, and predicts functions for several unstudied proteins in archaea.

To test these predictions, Buzzand his students have begun examining the dynamics of diffusion within eukaryoticcells. They will also look at proteins that are shared by eukaryotes andarchaea to test their functions and locations within archaeal cells, somethingthat will require overcoming the technical challenge of imaging these cells in sulphuric acidsolution at 76 °C, theirpreferred growth conditions. Meanwhile, David is using computational analysisof various genes to test competing ideas about how the ancestors ofmitochondria made a living.

Regardlessof whether the inside-out view prevails,testing these ideas will provide a better understanding of how eukaryotes cameto be. This may help to explain why eukaryotes evolved just once on Earth and, in so doing,will shape our expectations as to whether other planets might, in addition tomicroscopic prokaryote-like cells, harbour large and complex organisms such asthose that make life on Earth so enchanting.