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Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation. To identify mechanisms underlying suppression of multiple immune genes we undertook epigenetic analyses. We identified significantly differentially expressed microRNAs with known targets in suppressed genes. In addition, after searching regions upstream of the start of transcription of suppressed genes for common sequence motifs, we discovered novel enriched composite sequence patterns, which corresponded to Alu repeat elements, transposable elements known to have wide ranging influences on gene expression. Our findings suggest that to survive within infected cells, mycobacteria exploit a complex immune "molecular off switch" controlled by both microRNAs and Alu regulatory elements.

Developmental processes are thought to be highly complex, but there have been few attempts to measure and compare such complexity across different groups of organisms. Here we introduce a measure of biological complexity based on the similarity between developmental and computer programs. We define the algorithmic complexity of a cell lineage as the length of the shortest description of the lineage based on its constituent sublineages. We then use this measure to estimate the complexity of the embryonic lineages of four metazoan species from two different phyla. We find that these cell lineages are significantly simpler than would be expected by chance. Furthermore, evolutionary simulations show that the complexity of the embryonic lineages surveyed is near that of the simplest lineages evolvable, assuming strong developmental constraints on the spatial positions of cells and stabilizing selection on cell number. We propose that selection for decreased complexity has played a major role in moulding metazoan cell lineages.