Evolutionary analysis of the Leishmania major orthologues for the newly identified cyclic AMP response proteins.

Cyclic AMP (cAMP) signalling is largely noncanonical in kinetoplastids. With virtual absence of canonical cAMP effectors including cyclic nucleotide sensitive protein kinase A regulatory subunits. Through a number of RNAi screens, a group of novel cAMP-responsive effectors were identified from Trypanosoma with 11 members, assigned as cAMP Response Proteins (CARPs, CARP1 to 11). Four of the CARPs were reported earlier, recently the remaining seven were identified. Except for CARP3 and CARP11, the orthologues for other CARPs can be identified from Leishmania. An intricate evolutionary analysis performed earlier indicated CARP1 and CARP4 from Leishmania major comprise features of horizontally transferred genes. Aiming for comprehensive understanding of the evolution of CARPs, the study further extends the evolutionary analysis to newly annotated CARP orthologues from L. major. The study reveals the phylogenetic relation among kinetoplastid CARP orthologues and functional divergence. A systemic codon adaptation profiling suggested horizontal transfer for some of the CARPs. Alongside, structural analysis highlighted heterogeneity among the T. brucei and L. major orthologues.