Large-Scale Phylogenetic Analysis of Trypanosomatid Adenylate Cyclases Reveals Associations with Extracellular Lifestyle and Host-Pathogen Interplay

Genome Biol Evol. 2020 Dec 6;12(12):2403-2416. doi: 10.1093/gbe/evaa226.


Receptor adenylate cyclases (RACs) on the surface of trypanosomatids are important players in the host-parasite interface. They detect still unidentified environmental signals that affect the parasites' responses to host immune challenge, coordination of social motility, and regulation of cell division. A lesser known class of oxygen-sensing adenylate cyclases (OACs) related to RACs has been lost in trypanosomes and expanded mostly in Leishmania species and related insect-dwelling trypanosomatids. In this work, we have undertaken a large-scale phylogenetic analysis of both classes of adenylate cyclases (ACs) in trypanosomatids and the free-living Bodo saltans. We observe that the expanded RAC repertoire in trypanosomatids with a two-host life cycle is not only associated with an extracellular lifestyle within the vertebrate host, but also with a complex path through the insect vector involving several life cycle stages. In Trypanosoma brucei, RACs are split into two major clades, which significantly differ in their expression profiles in the mammalian host and the insect vector. RACs of the closely related Trypanosoma congolense are intermingled within these two clades, supporting early RAC diversification. Subspecies of T. brucei that have lost the capacity to infect insects exhibit high numbers of pseudogenized RACs, suggesting many of these proteins have become redundant upon the acquisition of a single-host life cycle. OACs appear to be an innovation occurring after the expansion of RACs in trypanosomatids. Endosymbiont-harboring trypanosomatids exhibit a diversification of OACs, whereas these proteins are pseudogenized in Leishmania subgenus Viannia. This analysis sheds light on how ACs have evolved to allow diverse trypanosomatids to occupy multifarious niches and assume various lifestyles.

Keywords: Kinetoplastida; adenylate cyclase; oxygen; phylogenetics; receptor; trypanosomatid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Evolution, Molecular*
  • Gene Duplication
  • Genome, Protozoan
  • Host-Pathogen Interactions / genetics*
  • Phylogeny*
  • Trypanosomatina / enzymology*
  • Trypanosomatina / genetics
  • Up-Regulation


  • Adenylyl Cyclases