Fig. 5

The evolutionary tree of Cdc48 supports the common ancestry of cryptophytes, alveolates, stramenopiles, and haptophytes (CASH lineages). The tree was calculated from the alignment of 687 Cdc48 sequences from a subset of eukaryotic species comprising archaeplastida and the CASH lineages. Statistical support values are annotated at selected inner edges. The tree splits into two main subsections. One subtree contains cytosolic Cdc48 working in the endoplasmic reticulum-associated protein degradation (ERAD) system. The other subtree includes a Cdc48 variant that transports proteins across the second-outermost membrane into the periplastidal compartment, a process referred to as symbiont-specific ERAD-like machinery (SELMA). The branching patterns supports the idea that SELMA Cdc48 is from a common red algal origin in CASH lineages. Note that the Cdc48 encoded by the nucleomorph of cryptophytes is more closely related to the ERAD Cdc48 of red algae. Although the sequences of SELMA Cdc48 diverged rapidly, its subtree still generally reflects the evolutionary relationships of the species. However, in the SELMA Cdc48 subtree, the missing lineages are those that have apparently lost their complex red plastid. Examples are ciliates, dinoflagellates, oomycetes, and cryptosporidians (Additional file 9: Table S3). All four nucleomorphs of cryptophyte algae contain genes for Cdc48 and nuclear VCP-like (NVL) [85], which is known to be involved in ribosome biogenesis. As the entire translation machinery is encoded in the nucleomorph, NVL might play a role in this process. Note that in previous studies, the nucleomorph-encoded Cdc48 and NVL were annotated as Cdc48a and b, respectively [85]. The nucleomorphs do not encode for N-ethylmaleimide sensitive factor (NSF) though, indicating that the red algae endosymbiont does not contain its own endomembrane system [76]