The interest in this paper lies primarily in the fact that it deals with a unicellular parasite (microsporidia) whose genome size is extremely small (3 Mbp for the haploid genome but divided into 11 chromosomes). The characteristics of this genome have opened new prospects in the evolutionary field, in the structural analysis of proteins, and in the host-parasite relationship.

“This work deals with Encephalitozoon cuniculi, the model of the “microsporidian world” (1300 species, 150 genera) having for hosts the representatives of all the animal kingdom including human, divided in all the environments (terrestrial, fresh water, marine water).”

Certain "prokaryotic" features suggested the position of microsporidia among the protists, at the basis of the eukaryotic tree, whilst other analysis placed them among fungi. The availability of the complete genome sequence has allowed us to confirm the placement in the crown of the phylogenetic tree among or near fungi. Later, a study on 99 sequences, belonging to 79 protein families, has shown that two-thirds of these sequences reveal a high frequency of fast-evolving genes.

The significant reduction, in size, of the majority of genes is quite amazing. This compaction is also interesting because it facilitates the structural analysis of important homologous proteins after crystallization, such as enzymes for mRNA capping or transcription factors.

Parasitism involved the elimination of metabolic pathways, while those remaining are shortened. The energy dependence with respect to the host is illustrated by the presence of a residual mitochondrion or mitosome, without a genome.

This paper described, for the first time, the complete genomic sequence of a eukaryote intracellular parasite.

I’ve worked for nearly 30 years on the pathogenic microsporidia of invertebrates, my clinical research interest had focused on the human microsporidia as it pertained to AIDS pathology. On one hand, the tools for diagnosis had proven weak and the treatments inefficient, whereas the physiological and biochemical data were reduced.

The systematic sequencing was thus, given the smallness of the genome, the best way to advance. Having started manually, with reduced team and financial means, the sequencing and the assembly of the first chromosome lasted three years.

The creation of Génoscope, the French National Sequencing Center, in 1997, made it possible to go quickly onto sequencing and its assembly, but the annotation was quite difficult because, at this time, only two eukaryotic genomes were available and the bio-informatic resources at our disposal were very much reduced. One very positive point is that the covered sequences have been exceptional—15 times—so the missing genes really miss.