Natural variation in a neural globin tunes oxygen sensing in wild Caenorhabditis elegans

Abstract

Behaviours evolve by iterations of natural selection, but we have few insights into the molecular and neural mechanisms involved. Here we show that some Caenorhabditis elegans wild strains switch between two foraging behaviours in response to subtle changes in ambient oxygen. This finely tuned switch is conferred by a naturally variable hexacoordinated globin, GLB-5. GLB-5 acts with the atypical soluble guanylate cyclases, which are a different type of oxygen binding protein, to tune the dynamic range of oxygen-sensing neurons close to atmospheric (21%) concentrations. Calcium imaging indicates that one group of these neurons is activated when oxygen rises towards 21%, and is inhibited as oxygen drops below 21%. The soluble guanylate cyclase GCY-35 is required for high oxygen to activate the neurons; GLB-5 provides inhibitory input when oxygen decreases below 21%. Together, these oxygen binding proteins tune neuronal and behavioural responses to a narrow oxygen concentration range close to atmospheric levels. The effect of the glb-5 gene on oxygen sensing and foraging is modified by the naturally variable neuropeptide receptor npr-1 (refs 4, 5), providing insights into how polygenic variation reshapes neural circuit function.

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

“…Persson et al reported that C. elegans globin homology glb-5 turns oxygen sensing triggering downstream signaling molecules. Therefore, many different globins in the C. elegans genome potentially contribute to the complexity to O 2 responses of C. elegans (16). Although hNgb is the homolog of GLB-13, hNgb exhibit new function against hypoxia injury as well as oxidative stress resistance in vertebrate during the evolution.…”

“…To date, the function of few of the globins is known. Recently, the function of globin-5, which encodes a neuronal globin protein, was identified by two research groups (15,16 (17).…”

Globins in Caenorhabditis elegans

“…NPR-1 modulates the O 2 sensing neurons AQR, PQR, and URX, which mediate avoidance of high O 2 and O 2 /CO 2 concentrations (21-11%) (17,(25)(26)(27). Not the variability in the NPR-1 receptor is responsible for the difference in foraging behavior between C. elegans strains, also the recently discovered globin, GLB-5, plays a role (15,17). GLB-5 is an O 2 sensing, hexacoordinated protein occurring naturally in two allelic variations: glb-5 (Haw) that was originally found in the C. elegans strain CB4856, isolated from an Hawaiian pineapple field, and glb-5 (Bri) that was discovered in the standard laboratory Bristol strain N2.…”

“…In bold, the aa that were excluded to construct the new model for GLB-5 Haw are given. The extra aa that were left out in the previous model are colored in grey (15). (d) Structural overlay of GLB-26 and GLB-6.…”

“…To date, only four C. elegans globins (GLB-1, GLB-5, GLB-6, and GLB-26) have been partially physicochemically characterized (14)(15)(16)(17). Two of them (GLB-1 and GLB-6) were crystallized, and their three-dimensional structure was solved.…”