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; VSG 4

More variations result from reshuffling segments of the genes for surface proteins.

Another method to switch expression is called end swapping. The megabase chromosomes and mini-chromosomes can exchange ends by recombination between blocks of repeated sequences just to the inside of the VSG genes (Fig. 19.17).This allows about 200 alternative VSG genes to be exchanged into the telomeric expression sites of the normal megabase chromosomes.

Not all VSG genes are found at the ends of the chromosomes, some are found as tandem arrays scattered throughout the megabase chromosomes. These are not accessible by chromosomal end-swapping and may only be used by gene conversion. (See Ch. 14 for the mechanism of gene conversion). All unexpressed copies of the VSG gene may be used to supply sequences for splicing into the VSG genes in the expression sites. Usually, the complete variable region of the VSG gene in the expression site is replaced with the complete variable region from one of the 1,000 extra copies (Fig. 19.18A). The constant region stays unchanged, as its name indicates. Later in infection, segments of various sizes from the spare VSG genes are used for replacement; anywhere from just a few base pairs to the whole gene may be used (Fig. 19.18B). Furthermore, just as with the genes encoding mammalian antibodies, point mutations occur in the VSG genes at higher than normal frequency. However, in the case of the VSG genes, the mutations occur during the segment-swapping process, not afterwards.

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