The axon degeneration gene SARM1 is evolutionarily distinct from other TIR domain-containing proteins

• Published in: Molecular genetics and genomics : MGG Vol. 292; no. 4; pp. 909 - 922
• Main Authors: Malapati, Harsha, Millen, Spencer M., J. Buchser, William
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2017; Springer Nature B.V
• Subjects: Amino Acid Sequence - genetics; Animal Genetics and Genomics; Animals; Armadillo Domain Proteins - genetics; Axons - pathology; Base Composition - genetics; Biochemistry; Biological Evolution; Biomedical and Life Sciences; Cytoskeletal Proteins - genetics; Databases, Genetic; Eagles - genetics; Esocidae - genetics; Evolution; Horses - genetics; Human Genetics; Life Sciences; Microbial Genetics and Genomics; Neurodegeneration; Original Article; Plant Genetics and Genomics; Proteins; Species; Synteny; Wallerian Degeneration - genetics; Wallerian axon degeneration; Innate immune; Neuroscience; Avian; Synteny
• ISSN: 1617-4615; 1617-4623
• DOI: 10.1007/s00438-017-1320-6

Many forms of neurodegenerative disease are characterized by Wallerian degeneration, an active program of axonal destruction. Recently, the important player which enacts Wallerian degeneration was discovered, the multidomain protein SARM1. Since the SARM1 protein has classically been thought of as an innate immune molecule, its role in Wallerian degeneration has raised questions on the evolutionary forces acting on it. Here, we synthesize a picture of SARM1 ’s evolution through various organisms by examining the molecular and genetic changes of SARM1 and the genes around it. Using proteins that possess domains homologous to SARM1, we established distances and Ka/Ks values through 5671 pairwise species–species comparisons. We demonstrate that SARM1 diverged across species in a pattern similar to other SAM domain-containing proteins. This is surprising, because it was expected that SARM1 would behave more like its TIR domain relatives. Going along with this divorce from TIR, we also noted that SARM1’s TIR is under stronger purifying selection than the rest of the TIR domain-containing proteins (remaining highly conserved). In addition, SARM1 ’s synteny analysis reveals that the surrounding gene cluster is highly conserved, functioning as a potential nexus of gene functionality across species. Taken together, SARM1 demonstrates a unique evolutionary pattern, separate from the TIR domain protein family.