Enlarge / Computer illustration of mitochondria, membrane-enclosed cellular organelles that produce energy.
Over 1.5 billion years ago, a monumental event occurred that forever altered the course of evolution on Earth. Two small, primitive cells merged and gave birth to a powerful structure known as the mitochondrion. Referred to as the “powerhouse of the cell” by schoolchildren, the mitochondrion provided a significant energy advantage to its host, paving the way for the emergence of complex, multicellular life forms. However, the mitochondrion is not the sole contributor to the complexity of eukaryotic cells. Other vital structures, such as the membrane-bound nucleus and internal membranes like the endoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, and vacuoles, play crucial roles in protein production, transportation, and recycling within the cell. But where did these structures come from? With limited evidence and distant historical events, cell biologists have faced a challenging task in unraveling the origins of this intricate cellular architecture. Thanks to new tools and techniques, researchers have begun shedding light on this mystery.
The concept that eukaryotes originated from the merger of two cells has been around for over a century, but it gained acceptance and recognition in the 1960s when evolutionary biologist Lynn Margulis introduced her theory of endosymbiosis. Margulis suggested that the mitochondrion likely originated from alphaproteobacteria, a diverse group of microbes. However, the nature of the original host cell remained a mystery. Scientists proposed that the host cell was already complex with various membrane structures, enabling it to engulf and ingest other substances through phagocytosis. Although this idea, known as the “mitochondria late” hypothesis, explains how the mitochondrion entered the host, it fails to clarify how and why the host cell became complex in the first place.
In 2016, evolutionary biologist Bill Martin, cell biologist Sven Gould, and bioinformatician Sriram Garg put forward a different hypothesis called the “mitochondria early” model. They argued that since primitive cells today lack internal membrane structures, it is unlikely that ancient cells possessed them over a billion years ago. Instead, they proposed that the endomembrane system, comprising the various components found within complex cells today, evolved shortly after an alphaproteobacterium symbiotically integrated into a relatively simple archaeal host cell. The membrane structures would have arisen from vesicles released by the mitochondrial ancestor. Gould, Garg, and Martin point out that free-living bacteria regularly shed vesicles, making it plausible for this process to continue within a host cell. Over time, these vesicles would have adapted and become specialized for the functions they perform in eukaryotic cells today. They would have fused with the host cell’s membrane, which explains why the eukaryote plasma membrane contains lipids with bacterial characteristics. According to biochemist Dave Speijer, these vesicles could have initially served as a means to sequester harmful reactive oxygen species generated by the endosymbiont, protecting the cell from their toxic effects. Additionally, they could have helped address the issue of interrupted genes resulting from the integration of the alphaproteobacterium’s DNA into the host genome. Gould, Garg, and Martin suggest that the membrane surrounding the nucleus, formed by flattened and wrapped vesicles, could have solved this problem by allowing mRNA splicing to occur within the nucleus, away from ribosomes in the cytosol.
While the “mitochondria early” hypothesis explains the evolution of endomembrane compartments, it does not fully account for how the alphaproteobacterium entered the host cell initially. Cell biologist Gautam Dey proposes an alternative idea known as the “inside-out” model. According to this model, the alphaproteobacterium and the archaeal cell would have coexisted in a symbiotic relationship for millions of years, each relying on the metabolic products of the other. The archaeal cell would have had long protrusions, similar to those observed in modern-day archaea living in close association with other microbes. The alphaproteobacterium would have nestled against these extensions, eventually becoming fully enclosed within them. Over time, the archaeal cell would have undergone spatial division of labor, with information-processing tasks concentrated in the central region containing the genome, while protein synthesis occurred in the cytosol within the protrusions. This model allows for a gradual evolution of regulatory mechanisms for the mitochondrion and other membrane compartments, ensuring their proper size and number. It also offers an explanation for the structure of the nucleus, particularly its large pores. The long protrusions, when viewed from the inside of an archaeal cell, would resemble openings that could naturally develop into large pores. Furthermore, the “inside-out” model clarifies how the alphaproteobacterium could have entered the archaeal host cell. However, this model still requires an additional step to transfer the alphaproteobacterium into the cytoplasm.
Evolutionary biologist Bill Martin objects to the “inside-out” model, highlighting the absence of an evolutionary pressure that would have led to the emergence of the nucleus and other membrane-bound compartments. Martin argues that the model is inverted and illogical. Both models agree on the origin of the mitochondrion from an alphaproteobacterium but hold contrasting views on the origin of the nucleus and other organelles. In the Gould, Garg, and Martin model, vesicles released by the evolving mitochondrion played a crucial role in the development of all membrane structures within the cell, while the “inside-out” model proposes a symbiotic relationship between an archaeal cell and the alphaproteobacterium, eventually resulting in the enclosure of the bacterium.
The origin of the nucleus remains a puzzle in both models. While they provide valuable insights into the evolution of cellular complexity, further research is needed to unravel the complete story of how these intricate structures emerged.
