Abstract
Cellular decision-making at the level of gene expression is a key process in the development and evolution of every organism. Variations in gene expression can lead to phenotypic diversity and the development of subpopulations with adaptive advantages. A prime example is the mutually exclusive activation of a single gene from within a multicopy gene family. In mammals, this ranges from the activation of one of the two immunoglobulin (Ig) alleles to the choice in olfactory sensory neurons of a single odorant receptor (OR) gene from a family of more than 1,000. Similarly, in parasites like Trypanosoma brucei, Giardia lamblia or Plasmodium falciparum, the process of antigenic variation required to escape recognition by the host immune system involves the monoallelic expression of vsg, vsp or var genes, respectively. Despite the importance of this process, understanding how this choice is made remains an enigma. The development of powerful techniques such as single cell RNA-seq and Hi-C has provided new insights into the mechanisms these different systems employ to achieve monoallelic gene expression. Studies utilizing these techniques have shown how the complex interplay between nuclear architecture, physical interactions between chromosomes and different chromatin states lead to single allele expression. Additionally, in several instances it has been observed that high-level expression of a single gene is preceded by a transient state where multiple genes are expressed at a low level. In this review, we will describe and compare the different strategies that organisms have evolved to choose one gene from within a large family and how parasites employ this strategy to ensure survival within their hosts.
Highlights
Pathogenic organisms, including eukaryotic parasites, have evolved numerous mechanisms to ensure their survival in the different, often hostile environments they encounter as they transition through their complex life cycles
Exclusive expression of genes from multicopy families appears to be a strategy conserved throughout eukaryotic evolution
As described in this review, several layers of control interact in a complex mechanism that results in the expression of a single family member
Summary
Pathogenic organisms, including eukaryotic parasites, have evolved numerous mechanisms to ensure their survival in the different, often hostile environments they encounter as they transition through their complex life cycles. Polycistronic organization of genes is not unique to the ES, but rather is a genome-wide feature that characterizes this ancient lineage of parasites (Clayton, 2019) Another peculiarity of vsg transcription is that it is carried out by RNA Polymerase I, a unique example of FIGURE 6 | Different ways in which VSG switching can be achieved in T. brucei in situ switching (A) where one promoter is silenced and another one is activated relies on epigenetic changes and is the only mechanism that does not involve recombination. To avoid antibody mediated clearance, these parasites can switch the expressed form VSP through mutually exclusive expression from a repertoire of around 200 vsp genes arranged as individual genes or in tandem arrays throughout the parasite’s genome (Figure 8) This enables them to display antigenic variation in a way similar to P. falciparum or T. brucei (Nash and Aggarwal, 1986; Nash, 2002). It was shown that active members of another clonally variant multicopy gene family, the rifins, relocate in the same active nuclear compartment as var genes (Howitt et al, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
