Fig. 4.

The Mis12 and NANO complex have a common ancestry. (A) Overview of the position of the Mis12 complex and NANO tetramers in the LECA kinetochore. (B) Cartoon of the consensus topology of all eight Mis12/NANO subunits, illustrating disordered and globular regions. (C) Profile-versus-profile hits with HHsearch (dark blue) and PRC (light blue) indicate that Mis12, Nnf1, Nsl1, Nkp1 and Nkp2 are homologous (SI Appendix, Text and Dataset S1). No sequence similarity between CenpU, Dsn1, and CenpQ with any of the other Mis12/NANO subunits was detected. (D) The subunits of the Mis12 and NANO display a high degree of similarity with respect to the (i) size and orientation of the head domains, (ii) length of the coiled coils, and (iii) presence of disordered N-terminal tails. Based on these three criteria, we defined a ‘Mis12’ and ‘Dsn1’ subtype. We propose that the Mis12 and NANO complex are the result of an ancient whole complex duplication, which was preceded by two rounds of Mis12/Dsn1 subtype duplication. Distances in the tree do not reflect measured distances but indicate a higher degree of sequence and structural variation for the Dsn1 type compared with the Mis12 type.