Major lipoprotein antigens, known as variable membrane surface lipoproteins
(Vsps), on the surface of the bovine pathogen Mycoplasma bovis were shown
to spontaneously undergo noncoordinate phase variation between ON and OFF e
xpression states. The high rate of Vsp phenotypic switching was also shown
to be linked with DNA rearrangements that occur at high frequency in the M.
bovis chromosome (I. Lysnyansky, R. Rosengarten, and D. Yogev, J. Bacterio
l. 178:5395-5401, 1996). In the present study, 13 single-copy vsp genes org
anized in a chromosomal cluster were identified and characterized. All vsp
genes encode highly conserved N-terminal domains for membrane insertion and
lipoprotein processing but divergent mature Vsp proteins. About 80% of eac
h vsp coding region is composed of reiterated coding sequences that create
a periodic polypeptide structure. Eighteen distinct repetitive domains of d
ifferent lengths and amino acid sequences are distributed within the produc
ts of the various vsp genes that are subject to size variation due to spont
aneous insertions or deletions of these periodic units. Some of these repea
ts were found to be present in only one Vsp family member, whereas other re
peats recurred at variable locations in several Vsps, Each vsp gene is also
5' linked to a highly homologous upstream region composed of two internal
cassettes. The findings that rearrangement events are associated with Vsp p
henotypic switching and that multiple regions of high sequence similarity a
re present upstream of the vsp genes and within the vsp coding regions sugg
est that modulation of the Vsp antigenic repertoire is determined by recomb
ination processes that occur at a high frequency within the vsp locus of M.
bovis.