Opinion: What do rescue experiments with heterologous proteins tell us and what not?

Abstract

AbstractThe recent progress in sequencing technology allowed the compilation of gene lists for a large number of organisms, though many of these organisms are hardly experimentally tractable when compared with well-established model organisms. One popular approach to further characterize genes identified in a poorly tractable organism is to express these genes in a model organism, and then ask what the protein does in this system or if the gene is capable of replacing the homologous endogenous one when the latter is mutated. While this is a valid approach for certain questions, I argue that the results of such experiments are frequently wrongly interpreted. If, for example, a gene from a parasitic nematode is capable of replacing its homologous gene in the model nematode Caenorhabditis elegans, it is often concluded that the gene is most likely involved in the same biological process in its own organism as the C. elegans gene is in C. elegans. This conclusion is not valid. All this experiment tells us is that the chemical properties of the parasite protein are similar enough to the ones of the C. elegans protein that it can perform the function of the C. elegans protein in C. elegans. Here I discuss this misconception and illustrate it using the analog of similar electric switches (components) controlling various devices (processes).