The Reduced Genome of the Parasitic Microsporidian Enterocytozoon bieneusi Lacks Genes for Core Carbon Metabolism

Abstract

Reduction of various biological processes is a hallmark of the parasitic lifestyle. Generally, the more intimate the association between parasites and hosts the stronger the parasite relies on its host's physiology for survival and reproduction. However, some systems have been held to be indispensable, for example, the core pathways of carbon metabolism that produce energy from sugars. Even the most hardened anaerobes that lack oxidative phosphorylation and the tricarboxylic acid cycle have retained glycolysis and some downstream means to generate ATP. Here we describe the deep-coverage genome resequencing of the pathogenic microsporidiian, Enterocytozoon bieneusi, which shows that this parasite has crossed this line and abandoned complete pathways for the most basic carbon metabolism. Comparing two genome sequence surveys of E. bieneusi to genomic data from four other microsporidia reveals a normal complement of 353 genes representing 30 functional pathways in E. bieneusi, except that only 2 out of 21 genes collectively involved in glycolysis, pentose phosphate, and trehalose metabolism are present. Similarly, no genes encoding proteins involved in the processing of spliceosomal introns were found. Altogether, E. bieneusi appears to have no fully functional pathway to generate ATP from glucose. Therefore, this intracellular parasite relies on transporters to import ATP from its host.

Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites

“…Microsporidia evolved distinctive genetic features, such as massive loss of genes, leading to the smallest known eukaryotic genomes (1). Remnants of mitochondria appear in microsporidian cells as DNA-free organelles called mitosomes (9,10) that perform simplified versions of the original mitochondrial functions, such as the assembly of iron-sulfur clusters (11), but no ATP production via citrate cycle and oxidative phosphorylation (12,13). For example, the human parasite Enterocytozoon bieneusi seems to have no fully functional pathway to generate ATP from glucose (12), relying on transporters to import ATP from its host.…”

“…Remnants of mitochondria appear in microsporidian cells as DNA-free organelles called mitosomes (9,10) that perform simplified versions of the original mitochondrial functions, such as the assembly of iron-sulfur clusters (11), but no ATP production via citrate cycle and oxidative phosphorylation (12,13). For example, the human parasite Enterocytozoon bieneusi seems to have no fully functional pathway to generate ATP from glucose (12), relying on transporters to import ATP from its host. These ATP transporters have been acquired by horizontal gene transfer (HGT) from intracellular parasitic bacteria (13).…”

Annotation of microsporidian genomes using transcriptional signals

“…None of the 70 newly predicted genes identified in E. bieneusi corresponded to core carbon metabolism, thereby confirming that this species has no fully functional pathway to generate ATP from glucose 12 .…”

“…Its genome, however, is still poorly documented 8 . Moreover, comparative genomic analysis using currently available microsporidian genomic data from other fully sequenced genomes (that is, Encephalitozoon cuniculi 9 , Encephalitozoon intestinalis 10 , Enterocytozoon bieneusi 11,12 , Nosema ceranae 13 Octosporea bayeri 14 and more recently, Encephalitozoon romaleae 15 , Encephalitozoon hellem 15 , Nematocida parisii 16 and Nematocida sp1 16 ) will provide a better understanding of specific host-parasite interactions and adaptation capacities.…”

Shrink it or lose it: balancing loss of function with shrinking genomes in the microsporidia

“…2 This reduction has been the focus of some attention due to the extremes to which microsporidia have gone in losing characteristics we normally expect in a eukaryote, and it is now clear that these strange parasites have taken several routes to this end. Here, two different ways to reduce biological complexity that have been recently described in three papers [6][7][8] will be illustrated and, by contrasting these, some of their broader implications will be discussed.…”