In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammals

Abstract

Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from 1-4. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.