All complex life, including plants, animals and fungi, consists if of eukaryotic cells, cells with a nucleus, transport mechanisms and often organelles like mitochondria that perform the functions an organism needs to stay alive and healthy. Humans have 220 different kinds of eukaryotic cells which control everything from thinking and locomotion to reproduction and immune defense.

Because of that commonality, the evolution of the eukaryotic cell is considered one of the most critical events in the history of life on Earth. Without it, earth populated entirely by prokaryotes, single-celled organisms such as bacteria and archaea, with no chance at all of filming "Guardians of the Galaxy" or celebrating Christmas.

It is generally agreed that eukaryotic cells arose from a symbiotic (mutualistic, not parasitic) relationship between bacteria and archaea. Archaea are similar to bacteria but have many molecular differences. Eukaryotes are organisms composed of more complex eukaryotic cells, which are characterized by an elaborate inner architecture, like the cell nucleus, where genetic information in the form of DNA is housed within a double membrane; mitochondria, membrane-bound organelles, which provide the chemical energy a cell needs to function; and the endomembrane system, which is responsible for ferrying proteins and lipids about the cell.

PALM composite of an E.coli bacterial cell shows the organization of proteins in the chemotaxis signaling network. Photo Credit: Jan Liphardt research group

Though many origin stories have been postulated since the discovery of organelles inside cells in the 1800s, prevailing belief is now that eukaryotes came to be when a bacterium was swallowed by an archaeon. The engulfed bacterium, it is said, gave rise to mitochondria, whereas internalized pieces of the outer cell membrane of the archaeon formed the cell's other internal compartments, including the nucleus and endomembrane system.

"The current theory is widely accepted, but I would not say it is 'established' since nobody seems to have seriously considered alternative explanations," according to David Baum, a University of Wisconsin-Madison professor of botany and evolutionary biologist. Along with University College London cell biologist Buzz Baum (his cousin), he formulated a new hypothesis for how eukaryotic cells evolved - the "inside-out" hypothesis of eukaryotic cell evolution.

The inside-out idea proposed by the Baums suggests that eukaryotes evolved gradually as cell protrusions, called blebs, reached out to trap free-living mitochondria-like bacteria. Drawing energy from the trapped bacteria and using bacterial lipids -- insoluble organic fatty acids -- as building material, the blebs grew larger, eventually engulfing the bacteria and creating the membrane structures that form the cell's internal compartment boundaries.

The Baums say their predictions are testable.

"First, the inside-out idea immediately suggested a steady stepwise path of evolution that required few cellular or molecular innovations. This is just what is required of an evolutionary model," says Buzz Baum. "Second, the model suggested a new way of looking at modern cells."

Modern eukaryotic cells, says Buzz Baum, can be interrogated in the context of the new hypothesis to answer many of their unexplained features, including why nuclear events appear to be inherited from archaea while other features seem to be derived from the bacteria.

The way cells work when they divide requires the interplay of molecules that have evolved over many millions of years to cut cells in two in the process of cell division. The same molecular functions could be repurposed in a way that conforms to the idea advanced by the Baums: Why spend the energy to remake something that was made thousands of years ago to pinch in a cell? The functions of these proteins just evolve and change as the organism's structure and function change.

There remains one giant problem for any new ideas about the origins of eukaryotic cells: Occam's razor and scant fossil record. "When it comes to individual cells, the fossil record is rarely very helpful," explains David Baum. "It is even hard to tell a eukaryotic cell from a prokaryotic cell. I did look for evidence of microfossils with protrusions, but, not surprisingly, there were no good candidates."

A potentially more fruitful avenue to explore, he suggests, would be to look for intermediate forms of cells with some, but not all, of the features of a full-blown eukaryote. "The implication is that intermediates that did exist went extinct, most likely because of competition with fully-developed eukaryotes."

However, with a more granular understanding of how complex cells evolved, it may be possible to identify living intermediates, says David Baum: "I do hold out hope that once we figure out how the eukaryotic tree is rooted, we might find a few eukaryotes that have intermediate traits."

"This is a whole new take (on the eukaryotic cell), which I find fascinating," notes UW-Madison biochemistry Professor Judith Kimble. "I have no idea if it is right or wrong, but they've done a good job of pulling in detail and providing testable hypotheses. That, in itself, is incredibly useful."