The complete sequence of the smallest known nuclear genome from the microsporidian Encephalitozoon intestinalis

Microsporidia are obligate intracellular parasites that have evolved an elaborate mechanism for invading animal host cells, but which have otherwise greatly reduced biological complexity. In particular, microsporidia possess the smallest autonomous nuclear genomes known (as opposed to nucleus derived organelles or nucleomorphs), and their 'anaerobic' core carbon metabolism is severely limited. Here we compare the extremes to which these two characteristics have evolved, and contrast how their reduction has either proceeded within the constraints of an unchanging set of functions, or has reduced the functional capabilities of the cell. Specifically, we review how the smallest known nuclear genome, the 2.3 Mbp genome of Encephalitozoon intestinalis, has arrived at this diminutive form without significantly affecting its protein-coding complexity in comparison with closely related, larger genomes. In contrast to this, Enterocytozoon bieneusi has a relatively large genome, and yet has lost all enzymes necessary to synthesize ATP from sugar-imposing a major limitation on the functional capabilities of the cell. The extremity of this reduction demands a re-evaluation of metabolic processes in other microsporidia: although pathways such as glycolysis are present, comparative genomic data suggest they may not play the cellular role that they are generally assumed to play.