The Caenorhabditis globin gene family reveals extensive nematode-specific radiation and diversification

Abstract

BackgroundGlobin isoforms with variant properties and functions have been found in the pseudocoel, body wall and cuticle of various nematode species and even in the eyespots of the insect-parasite Mermis nigrescens. In fact, much higher levels of complexity exist, as shown by recent whole genome analysis studies. In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles.ResultsIn the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi and EST data from several other nematode species to study the evolutionary history of the nematode globin gene family. We find a high level of conservation of the C. elegans globin complement, with even distantly related nematodes harboring orthologs to many Caenorhabditis globins. Bayesian phylogenetic analysis resolves all nematode globins into two distinct globin classes. Analysis of the globin intron-exon structures suggests extensive loss of ancestral introns and gain of new positions in deep nematode ancestors, and mainly loss in the Caenorhabditis lineage. We also show that the Caenorhabditis globin genes are expressed in distinct, mostly non-overlapping, sets of cells and that they are all under strong purifying selection.ConclusionOur results enable reconstruction of the evolutionary history of the globin gene family in the nematode phylum. A duplication of an ancestral globin gene occurred before the divergence of the Platyhelminthes and the Nematoda and one of the duplicated genes radiated further in the nematode phylum before the split of the Spirurina and Rhabditina and was followed by further radiation in the lineage leading to Caenorhabditis. The resulting globin genes were subject to processes of subfunctionalization and diversification leading to cell-specific expression patterns. Strong purifying selection subsequently dampened further evolution and facilitated fixation of the duplicated genes in the genome.

GLB‐13 is associated with oxidative stress resistance in caenorhabditis elegans

“…Neuronal activities consume lots of oxygen, and C. elegans globin-like proteins are mainly expressed in these cells (10). Recently, we observed that the glb-13 mutant is not sensitive to hypoxia compared to wildtype worms, and Punc-119::hNgb-Tg worms failed to suppress hypoxic death of embryos, larvae, and adult worms (unpublished data).…”

“…C. elegans has 302 neuronal cells, which comprise one-third of somatic cells. Interestingly, the globin-like proteins are mainly expressed in neurons of C. elegans (10,11). It was reported that behavioral responses of C. elegans to chemicals and gases are controlled by gene activities that are mostly deployed in neurons (12)(13)(14).…”

“…In C. elegans genome, F19H6.2(glb-13) displays significant sequence similarity to Ngb as revealed by BLAST searches with the similarity e-value to be 5.4 eÀ07 (9). Like Ngb, glb-13 is also specifically expressed in neurons and considered as a homolog of neuroglobin based on sequence analysis (3,10). Therefore, we hypothesized that glb-13 gene in C. elegans might have a neuroprotective role against ROS-induced injury, similar to Ngb.…”

Globins in Caenorhabditis elegans

“…These GFP reporter assays showed that the globins were expressed in distinct, mostly nonoverlapping sets of cells (Supporting Information Table S2) (9). Most of them were expressed in neuronal cells in the head and tail portions of the body and in the nerve cord.…”

“…(12). The 33 globins can be aligned to fit the globin fold, but additional N-terminal, C-terminal, and interhelical loops create a wide structural diversity among them (Supporting Information Table S1, (9)). Because of these additional aa, the total globin length ranges from 158 aa (GLB-25) to 542 aa (GLB-33).…”