Fig. 7: Phylogeny of NRBP1/2 homologs generated using maximum likelihood.

a Maximum likelihood phylogeny of the IQ-TREE analysis comprising 2,065 quality- filtered NRBP proteins belonging to 663 species and including 417 amino acid positions. Orthologues of human NRBP2 are recovered as a monophyletic group with perfect bootstrap support (blue). All NRBP2 belong to the Euteleostomi. Its sister clade contains all orthologues of human NRBP1 derived from vertebrate taxa (orange) and has perfect bootstrap support as well. The NRBP sequence of the sponge Amphimedon queenslandica was chosen as outgroup taxon. Branch lengths are amino acid substitutions per site. b The distance from leaf to root was determined in (a) for all NRBP proteins. The NRBP2 clade accumulated considerably more amino acid substitutions than the NRBP1 clade and the average invertebrate NRBP protein. A consequence of this is that all invertebrate NRBP proteins are more similar to human NRBP1 than they are to human NRBP2. n = 461 for NRBP invertebrate, n = 933 for NRBP1, n = 670 for NRBP2, n = 203 for NRBP2 mammal. Statistical significance was assessed using two-sided Welch’s t-tests with Benjamini–Hochberg correction for multiple comparisons. c Plot of BlastP bit scores resulting from 462 comparisons of invertebrate NRBP either to human NRBP1 or to human NRBP2. Statistical significance was determined using a two-sided paired t-test (n = 462). No multiple comparison adjustment applied. d HPO-11 from C. elegans enhances L1 activity in HeLa cells. n = 3 biological replicates. Data are presented as mean values ± SEM. Two-sided unpaired t-test; no multiple comparison adjustment applied.