UC San Diego

Homolog transcription factors have emerged from genome duplication events in evolutionary history, resulting in the co-existence of many similar proteomic pairs in eukaryotic cells. Although a large number of homologs have diversified over time to obtain unique roles from their partners, others have remained relatively conserved, limiting their downstream interactions to identical target genes. The functional advantages arising from the retention of such redundancy in the proteome have remained elusive in the context of biological design. Here, using quantitative single-cell imaging and microfluidics, we find that the yeast general stress response transcription factor Msn2 and its seemingly redundant homolog Msn4 play distinct roles in mediating the gene expression in response to environmental stressors, which is contrary to previous belief. We observe at the single cell level, that although Msn4 exhibits identical translocation dynamics to Msn2, the level of its nuclear translocation during stress is significantly more heterogeneous than that of Msn2. As a result, while target genes with fast kinetics are expressed in most of the cells, slower target genes are induced only in the fraction of cells with high Msn4 activity. We further show that this Msn4-dependent diversification in the gene expression program in single cells is important for the adaptive response to environmental stresses.