Naegleria is considered to be one of the earliest diverging protists with mitochondria. Nuclear rRNA phylogenies support this view: in such trees, heterolobosea emerge at the base of mitochondria-bearing eukaryotes, together with trypanosomatids and euglenoids. All three taxa feature extraordinarily long branch lengths (e.g., Sogin et al. (1996), Microbiologica 12:17-28; Abstract).
In trees based on mitochondrial proteins, N. gruberi also appears to be a deeply diverging eukaryote, basally associated with the jakobids (BFL, unpublished results); however, bootstrap support for this affiliation is low (< 65%). Sequences from other heteroloboseans, such as Macropharyngomonas and another species of Malawimonas, will be needed to confirm/reject this postulated relationship of N. gruberi within the mitochondrial lineage.