The Structure And Characteristics Of Marine Mammal IGHC Gene Locus And Its Adaptive Evolution

Marine mammals are one of the most mysterious groups in the history of mammalian evolution.Their terrestrial ancestors re-entered in the aquatic environment at different times and lived to complete-or semi-aquatic life.After a long-term evolution,marine mammals have developed a series of morphological and physiological features that adapt to the aquatic environment.In particular,their immune systems have been able to respond to pathogenic microorganisms that are lived in marine environment differing from the terrestrial one.Immunoglobulins(Igs)are a class of glycoprotein molecules that are involved in humoral immune system,Typically,Igs compose two identical heavy(IgH)and two identical light chains(IgL),and both heavy and light chains can be divided into two regions,i.e.,the constant region and the variable region,based on the variability of amino acid sequences.Immunoglobulin heavy chain constant region(IGHC)specifies effector functions,such as activation of complement,binding Fc(fragment crystallizable)receptors,ADCC and type I hypersensitivity,playing an irreplaceable important role in immune defense.Mammals generally have five IgH isotypes,including IgM,IgD,IgG,IgE,and IgA,and they are encoded by the IGHM,IGHD,IGHG,IGHE and IGHA genes respectively.However,the evolutionary mechanism of IGHC genes in marine mammals remains unclear.Therefore,we take 10 representative species of marine mammals(7 cetaceans +2 pinnipeds +1 manatee)and 16 terrestrial mammals as the research objects.We obtained the IGHC gene sequeces of these species by scanning the available genome assemblies or retrieving that from the databases.Bioinformatics and comparative genomics analysis were conducted to explore the genomic organization of IGHC genes in marine mammal genomes,and the selection pressures of pathogenic micobes on IGHC in different species was analyzed and compared.The results of this study are as follows:1.The genomic organization of marine mammal IGHC genes is resemble its closely related terrestrial mammals:?marine mammals have 5 typical IGHC genes and are arranged on the chromosomes in the form of 5'-C?-C?-C?-C?-C?-3'.?we found that the first domain(CHI)of IGHM and the CHI of IGHD of cetaceans are highly homologous.These findings indicate that the structure of IGHC loci is highly conserved across different mammals.2.The number of IGHC genes in mammals varied greatly,ranging from 4 in short-tailed possums and shrews to 16 in rabbits.Particularly,the number of copies of IGHG genes is different across species,and the IGHG gene within the same species clustered together firstly,then clustered with the gene from other species,which support the view that IGHG genes is species-specifically duplicated during the course of mammalian evolution.These results suggest that the IGHC gene in different species adaptively evoluted in responding to the pathogenic microbes specifically occured in their respective habitats.3.Sigals of positive selection were massively detected on the IGHM,IGHE and IGHA genes,suggesting that IGHC genes were subjected to adaptive evolution across mammalian species.In addition,the Branch and Branch-site model analyses revealed that stronger selective pressures acting on IGHC genes in terrestrial mammals,which support the view that the pathogenic microbes in terrestrial environment are more diverse than that in marine environment.Interesting,the signs of positive selection were mainly concentrated in artiodactyla,perissodactyla and chiroptera,which may attribute to the artificial selection in domestic animals and the co-evolution of bats and viruses,respectively.In the present study,the genomic organization of IGHC was characterized in marine mammals,and the selection analysis on IGHC genes revealed the evolutionary pattern of immune genes in marine mammals,which deepened our understanding of the aquatic adaptation mechanism in marine mammals.