Fast, adaptive evolution at a bacterial host-resistance locus: the PFam54 gene array in Borrelia burgdorferi.
Microbial pathogens have evolved sophisticated mechanisms for evasion of host innate and adaptive immunities. PFam54 is the largest paralogous gene family in the genomes of Borrelia burgdorferi, the Lyme disease bacterium. One member of PFam54, the complement-regulator acquiring surface proteins 1 (BbCrasp-1), is able to abort the alternative pathway of complement activation via binding human complement-regulator factor H (FH). The gene coding for BbCRASP-1 exists in a tandem array of PFam54 genes in the B. burgdorferi genome, a result apparently of repeated gene duplications. To help elucidate the functions of the large number of PFam54 genes, we performed phylogenomic and structural analyses of the PFam54 gene array from ten B. burgdorferi genomes. Analyses based on gene tree, genome synteny, and structural models revealed rapid adaptive evolution of this array through gene duplication, gene loss, and functional diversification. Individual PFam54 genes, however, do not show high intra-population sequence polymorphisms as genes providing evasion from adaptive immunity generally do. PFam54 members able to bind human FH are not monophyletic, suggesting that human FH affinity, however strong, is an incidental rather than main function of these PFam54 proteins. The large number of PFam54 genes existing in any single B. burgdorferi genome may target different innate-immunity proteins of a single host species or the same immune protein of a variety of host species. Genetic variability of the PFam54 gene array suggests that universally present PFam54 lineages such as BBA64, BBA65, BBA66, and BBA73 may be better candidates for the development of broad-spectrum vaccines or drugs than strain-restricted lineages such as BbCRASP-1.
Wywial
Ewa
E
Department of Biology, The Graduate Center of the City University of New York, 365 Fifth Avenue, New York, NY 10016, USA.
Haven
James
J
Casjens
Sherwood R
SR
Hernandez
Yozen A
YA
Singh
Shaneen
S
Mongodin
Emmanuel F
EF
Fraser-Liggett
Claire M
CM
Luft
Benjamin J
BJ
Schutzer
Steven E
SE
Qiu
Wei-Gang
WG
D000220:Adaptation, Biological / Q000235:genetics*; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D025065:Borrelia burgdorferi / Q000235:genetics*; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D014644:Genetic Variation; D054884:Host-Pathogen Interactions / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors
D001426:Bacterial Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D017242:Complement Factor H