Rapid evolution of genes coding for variant surface glycoproteins in trypanosomes

Area of Science:

• Molecular Biology
• Parasitology
• Genetics

Background:

• Trypanosoma brucei employs variant surface glycoproteins (VSGs) for immune evasion.
• The genetic basis and conservation of VSG genes are crucial for understanding trypanosome adaptability.

Purpose of the Study:

• To investigate the conservation of nuclear genes encoding specific VSGs in related Trypanosoma brucei stocks.
• To assess the evolutionary rates of a subset of VSG genes.

Main Methods:

• Utilized cloned complementary DNA (cDNA) probes derived from Trypanosoma brucei stock 427 VSG messenger RNAs (mRNAs).
• Performed Southern blot hybridization of cDNA probes to nuclear DNA from various trypanosome stocks.
• Analyzed conservation of restriction endonuclease cleavage sites flanking and within the target VSG genes.

Main Results:

• One VSG gene (117) was found to be highly conserved, present and largely unaltered in 11 out of 12 stocks examined.
• A second VSG gene (118) was absent in five stocks, and the seven stocks containing it showed four distinct forms differing in restriction sites.
• A third VSG gene (221) was specific to Trypanosoma brucei stock 427, absent in the other 11 stocks.

Conclusions:

• A subset of VSG genes evolves at a significantly high rate within Trypanosoma brucei.
• The observed rapid evolution and variation in VSG gene presence and structure support a hypothesis of local hypermutagenesis driving antigenic diversity.