Table 1.

The co-emergence of NOX enzymes and multicellularity might also correlate with the origin of DNA-based defense strategies.

Representative organisms from both eukaryotes and prokaryotes [see Ref. (18) for detailed presentation] were collected and organized by major branches in taxonomy. The number of NOX enzymes in each organism is indicated and color coded. Unicellular and multicellular organisms are indicated by a “NO” and “YES,” respectively. Two organisms that are at the transition between the two life forms or have both life forms are indicated as “Transition.” One exception is Naegleria gruberi, a single-celled organism well known for its capacity to transition from an amoeboid to a flagellated form. It is a free-living organism, but closely related to pathogenic, parasitic species. Therefore, it is plausible that the NOX gene of Naegleria might have been acquired from its host via horizontal gene transfer or that it derives from an organism that was at the transition to multicellularity, but lost this characteristic of multicellular organisms as it specialized to its environment. The discovery of NOX-dependent ET generation in the multicellular form of the amoeba D. discoideum, an organism that is at the transition to multicellularity, combined to the recognition of the apparent coemergence of multicellularity and NOX enzymes indicate that the origin of ET formation might be traced back to the emergence of multicellular organisms. It also suggests that variants and diverse evolutions of DNA-based defense strategies might be identified in other organisms with functional NOX enzymes, both in primitive metazoans and organisms close to the transition to multicellularity.