1.A.151.  The Ubiquitous Insect Chemoreceptor (UICR or 7TMIC) Family 

Himmel et al. 2023 presented a pipeline for the identification and characterization of distant homologs, and applied it to 7-transmembrane-domain ion channels (7TMICs), a protein group founded by insect odorant and gustatory receptors. Previous sequence and limited structure-based searches identified putatively related proteins, mainly in other animals and plants. However, very few 7TMICs have been identified in non-animal, non-plant taxa. Moreover, these proteins' remarkable sequence dissimilarity made it uncertain whether disparate 7TMIC types (Gr/Or, Grl, GRL, DUF3537, PHTF, and GrlHz) are homologous or convergent, leaving their evolutionary history unresolved. The pipeline identified thousands of new 7TMICs in archaea, bacteria, and unicellular eukaryotes. Using graph-based analyses and protein language models to extract family-wide signatures, we demonstrate that 7TMICs have structure and sequence similarity, supporting homology. Through sequence- and structure-based phylogenetics, eukaryotic 7TMICs were classified into two families (Class-A and Class-B), which are the result of a gene duplication predating the split(s) leading to Amorphea (animals, fungi, and allies) and Diaphoretickes (plants and allies). 7TMICs are a cryptic superfamily, with origins close to the evolution of cellular life.