What has DNA sequencing revealed about the VSG expression sites of African trypanosomes?

Antigenic variation is crucial for the survival of African trypanosomes in mammals and involves switches in expression of variant surface glycoprotein genes, which are co-transcribed with a number of expression-site-associated genes (ESAGs) from loci termed ‘bloodstream expression sites’ (BESs). Trypanosomes possess multiple BESs, although the reason for this (and why ESAGs are resident in these loci) has remained a subject of debate. The genome sequence of Trypanosoma brucei, released in 2005, did not include the BESs because of their telomeric disposition. This gap in our knowledge has now been bridged by two new studies, which we discuss here, asking what has been revealed about the biological significance of BES multiplicity and ESAG function and evolution.