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The hydrogen hypothesis is a model proposed by William F. Martin and Miklós Müller in 1998 that describes a possible way in which the mitochondrion arose as an endosymbiont within a prokaryote (an archaea), giving rise to a symbiotic association of two cells from which the first eukaryotic cell could have arisen.

According to the hydrogen hypothesis:

The hypothesis differs from many alternative views within the endosymbiotic theory framework, which suggest that the first eukaryotic cell cells evolved a nucleus but lacked mitochondria, the latter arising as a eukaryote engulfed a primitive bacterium that eventually became the mitochondrion.

The hypothesis attaches evolutionary significance to hydrogenosomes and provides a rationale for their common ancestry with mitochondria. Hydrogenosomes are anaerobic mitochondria that produce ATP by, as a rule, converting pyruvate into hydrogen, carbon dioxide and acetate. Examples from modern biology are known where methanogens cluster around hydrogenosomes within eukaryotic cells. Most theories within the endosymbiotic theory framework do not address the common ancestry of mitochondria and hydrogenosomes.

The hypothesis provides a straightforward explanation for the observation that eukaryotes are genetic chimeras with genes of archaeal and eubacterial ancestry. Furthermore, it would imply that archaea and eukarya split after the modern groups of archaea appeared. Most theories within the endosymbiotic theory framework predict that some eukaryotes never possessed mitochondria. The hydrogen hypothesis predicts that no primitively mitochondrion-lacking eukaryotes ever existed. In the 10 years following the publication of the hydrogen hypothesis, this specific prediction has been tested many times and found to be in agreement with observation.


  • López-Garćia P and Moreira D (1999). "Metabolic symbiosis at the origin of eukaryotes". Trends Biochem Sci. 24 (3): 88–93. doi:10.1016/S0968-0004(98)01342-5.  
  • Martin W and Müller M (1998). "The hydrogen hypothesis for the first eukaryote". Nature 392 (6671): 37–41. doi:10.1038/32096.  
  • Poole AM and Penny D (2007). "Evaluating hypotheses for the origin of eukaryotes". Bioessays 29 (1): 74–84. doi:10.1002/bies.20516.  
  • Embley TM and Martin W (2006). "Eukaryotic evolution, changes and challenges". Nature 440: 623–630. doi:10.1038/nature04546.  

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