Where have all the regulations gone?

Posted by Hamed Shateri Najafabadi

Three weeks ago, Lila Koumandou and her colleagues from University of Cambridge reported a thorough analysis of  the transport-associated transcriptome of Trypanosoma brucei, a work conducted at Mark Field’s lab. Although previous works have also addressed developmental regulation of mRNA level in T. brucei using microarray analysis of transcriptome, this is the first report in which expression profiles of a wide range of genes are examined at different conditions, including geneticly manipulated cells and varying environmental conditions – To have an idea how such analysis can revolutionize the knowlede of regulatory mechanisms of an organism, take a look at this classic paper by Beer and Tavazoie. The results section of Lila and colleagues’ paper start with the expected corroboration of previous studies, indicating that many genes in T. brucei are developmentally regulated at mRNA level. However, the surprise is waiting where we find out that the transcriptome of T. brucei shows a very limited response to the altered environment and genetic background. Nevertheless, protein levels change in accordance to the alterations. These results suggest that within a life stage, regulation of mRNA level has little to say when the organism needs to adapt to a different milieu, and perhaps the answer should be sought at translation and post-translational levels.

The field of proteomics is yet, if not naive, not as mature as genomics. Even qualitative determination of the set of proteins being expressed by a cell cohort is a tremendous task. WIth advances in the resolution and throughput of mass spectrometry techniques and differential labeling of protein samples, it has become more feasible to quantitatively compare the proteomes of several samples. Yet, analysis of the proteome of T. brucei, with the same extent as what Lili and her colleagues have presented for its transcriptome, requires resources way beyond the affordability of most of the labs that work in this field. In fact, such analysis has not been done yet for any organism, and it is reasonable to assume that the first would be a model organism, rather than a trypanosomatid.

Transcriptional flexibility and inflexibility in differentiation and responsiveness. Upper panel: flexible system. Gene cohorts 1 and 3 are developmentally regulated, and either highly expressed or not expressed; examples of these types of gene products are the trypanosome surface antigens, VSG in the bloodstream form (red) and procyclin in the insect stage (green). The vast majority of genes fall into cohort 2, where, for example, either small or large changes to transcription could result from alterations to the environment (light and dark blue), or a more continually altering transcriptional profile is present that may seek to track changing conditions (purple). This behavior may propagate from one life stage to the next (light and dark blue) or be lost (purple) resulting in altered transcriptional flexibility for genes between life stages. Such a profile is found in higher eukaryotes, including humans and yeast, and probably also many protists, including E. gracilis. Lower panel: inflexible system. In this model gene cohorts 1 and 3 behave as before, but transcription of the genes in cohort 2 remains unchanged. The relative levels of mRNAs from the genes in this cohort may remain constant following differentiation (light blue) or be significantly altered (dark blue and purple). Such a profile is observed here for T. brucei and has been reported previously for P. falciparum, and is potentially a result of a parasitic life style where the host is responsible for provision of a homeostatic environment.

Koumandou et al. BMC Genomics 2008 9:298   doi:10.1186/1471-2164-9-298