The Evolutionary Of Chemokine CXCL16 And Its Receptor CXCR6 In Primates And Rodents

The immune system is composed of many cell types that collectively defend the body against pathogens,including parasites,fungi,bacteria,and viruses,as well as cancerous cells.Attraction and migration of the immune cells to the site of immune surveillance and activation play pivotal roles in both innate and adaptive immunity.In addition,the motility of these cells forms the basis for their development within specific microenvironments.It has been well recognized that members of the chemokine superfamily,including a large number of chemokines and their adhesion receptors,function as critical regulators for the function and organization of these immune responses system.Of these,the chemokine CXCL16 exists in either a membrane-bound or soluble form.As the sole receptor for CXCL16,CXCR6(also known as STRL33,Bonzo,or TYMSTR)is a typical seven-transmembrane protein,which can couple and activate the G-proteins.CXCL16 has shown particular competence in cell-cell adhesion,which is at least partially due to its physical interaction with CXCR6 in a concordant manner.Besides the the CXCL16/CXCR6 axis in the chemoattraction,the ligand functions solely as a scavenger receptor for phosphatidylserine and oxidized low-density lipoprotein and contributes to the phagocytosis of bacteria and transport class D Cp G oligonucleotides into endosomal compartments,consequently activating antigen presenting cells.Moreover,CXCR6 serves as a principal coreceptor for the entry of simian immunodeficiency virus(SIV)and human immunodeficiency virus(HIV)into host cells.Despite the progresses in elucidating the signatures of CXCL16 and its receptor under physiological and pathological conditions,a comprehensive description is currently lacking as to molecular mechanism of their functions because of multiple barriers,such as intrinsic difficulties in studying membrane proteins and vastly different manners of known chemokines and their receptors.Taking into consideration the arms race between the host system and pathogens,the evolutionary characteristics of the chemokine and its receptor could be a perfect introduction to their molecular implementation in immune responses.In the present study,the genetic variation information of CXCL16 and CXCR6 from the important primate and murine laboratory animals was analyzed.The coding regions of CXCL16 and CXCR6 gene were determined and collected from25 primate species(including important laboratory animals Pan troglodytes and Macaca mulatta)and 16 rodent subfamily species(including important laboratory animals Rattus norvegicus and Mus musculus).We implemented comparisons of synonymous and nonsynonymous substitution rates,ML analysis,Mc Donald-Kreitman test,DIVERGE and/or Tajima's test to evaluate their genetic evolution characteristics in these taxa.The main results are as follows:(1)In primates,CXCL16 and CXCR6 took place adaptive genetic diversification with the separation of cercopithecoids and hominoids,but showed conservative characteristics in the previous and subsequent evolution process,(2)There are multiple amino acid sites occurred adaptive genetic diversification in CXCL16 and CXCR6 with the separation of cercopithecoids and hominoids,The divergence-related amino acid sites locates on chemokine domain(sites 91 and 96)and mucin-like domain(sites 126,128,133,192,199,and 212)respectively.In CXCR6,there are four amino acid sites were influenced by adaptive selection,which lie in N-terminus(sites 6 and 7)and the fourth and sixth transmembrane helixes(sites 151 and 245),(3)For murine rodents,our results indicate that adaptive selection has frequently contributed to genetic diversity of both CXCL16 and CXCR6 that is asynchronous with a relative dependence between these genes.Of note,this signature is radically different from the lineage-specific and concordant adaptive diversity of the primate homologues of these genes,which was reported in a previous study,(4)For murine CXCR6,There are seven amino acid sites occurred adaptive diversification.The adaptively selected sites clustered in the extracellular N-terminus(sites6,8,and 26)and the fourth transmembrane helix and its flanking cytoplasmic-and extracellular-side loops.In conclusion,we quantified the genetic variations of CXCL16 and CXCR6 in primates and murine rodents.The results revealed that adaptive selection has frequently contributed to radically different genetic diversities of both CXCL16 and CXCR6 in these taxa.The observations from primates and murines give credence to the notion that case-by-case studies would be necessary to comprehensively understand the context-specific evolution of CXCL16 and CXCR6 and,likewise,of other chemokines and their receptors.The evolutionary trajectories and characteristics provided hints for the structural nature of the CXCL16-CXCR6 interplay and potentially CXCR6-mediated entry of pathogens in murine mammalian models.