E. histolytica lacks mitochondria, probably through secondary loss, and the sequencing of the E. histolytica genome did not reveal evidence of a mitochondrial genome. Instead, the parasite derives energy from glycolysis and fermentation. More than two decades ago, Reeves defined the fermentation pathway of E. histolytica . During the ensuing years, as specific enzymes in this pathway were identified by molecular tools, it became clear that many of the pathway components resembled prokaryotic enzymes rather than those found within higher eukaryotes [12,13]. This finding led to the concept that lateral gene transfer from prokaryotes provided the enzymes necessary for fermentation and enabled ameba to dispense with mitochondria . Similar lateral gene transfer events, although apparently from different prokaryotic donors, seem to have occurred in other amitochondriate protozoans, including G. lamblia and the genitourinary pathogen Trichomonas vaginalis. Following the completion of the genome project, the true importance of lateral gene transfer in shaping E. histolytica biology has become clear. Using phylogenetic screens, Loftus et al.  identified 96 E. histolytica genes that seem to represent cases of recent prokaryotic-to-eukaryote gene transfer. Most of these genes encode proteins involved in carbohydrate and protein metabolism, and many seem to expand the range of available energy substrates. How lateral gene transfer occurred, especially in an organism that has been so resistant to attempts to introduce homologous recombination, remains a fascinating and open question.
With the attention on lateral gene transfer, it is important to emphasize that one of the most crucial results of the genome project was the generation of an E. histolytica ‘metabolome’, whereby the identified genes were used to predict all of the parasite metabolic pathways . This will be a valuable tool for researchers, and the gaps in these pathways might point to novel activities and/or vulnerabilities that could be exploited for new anti-amebic therapies.