Spatiotemporal Patterns of Gene Expression During Development of a Complex Colony Morphology

Clonal communities of single celled organisms, such as bacterial or fungal colonies and biofilms, are spatially structured, with subdomains of cells experiencing differing environmental conditions. In the development of such communities, cell specialization is not only important to respond and adapt to the local environment but has the potential to increase the fitness of the clonal community through division of labor. Here, we examine colony development in a yeast strain (F13) that produces colonies with a highly structured “ruffled” phenotype in the colony periphery and an unstructured “smooth” phenotype in the colony center. We demonstrate that in the F13 genetic background deletions of transcription factors can either increase (dig1 deletion, sfl1 deletion) or decrease (tec1deletion) the degree of colony structure. We identify genes responding additively and non-additively to the genotype and spatiotemporal factors and cluster these genes into a number of different expression patterns, including patterns that correlate closely with the degree of colony structure in each sample and include genes with known roles in the development of colony structure. Individual deletion of 26 genes sampled from different clusters identified 5 with strong effects on colony morphology (BUD8, CIS3, FLO11, MSB2 and SFG1), all of which eliminated or greatly reduced the structure of the F13 outer region.单细胞生物的克隆群落（clonal communities），如细菌菌落、真菌菌落及生物膜，均具有空间结构特征，其细胞所处的不同亚区域会面临各异的环境条件。在这类群落的发育进程中，细胞特化不仅是响应并适配局部环境的关键机制，还可通过劳动分工提升克隆群落的适应度（fitness）。在此，我们以酵母菌株F13为研究对象，该菌株形成的菌落其边缘呈现高度结构化的"褶皱"表型（phenotype），而菌落中心则表现为非结构化的"光滑"表型。我们证实，在F13的遗传背景下，转录因子（transcription factors）的基因缺失可对菌落结构程度产生双向调控：其中dig1基因缺失、sfl1基因缺失可增强菌落结构，而tec1基因缺失则会削弱菌落结构。我们鉴定出了对基因型（genotype）与时空因子（spatiotemporal factors）分别呈现加性效应与非加性效应的基因，并将这些基因划分为多种不同的表达模式，其中部分模式与各样本中的菌落结构程度密切相关，且涵盖了已知在菌落结构发育中发挥功能的基因。我们从上述不同基因簇（gene clusters）中选取26个基因开展单基因缺失实验，其中5个基因（BUD8、CIS3、FLO11、MSB2及SFG1）对菌落形态（colony morphology）具有显著调控效应，其缺失均会消除或大幅削弱F13菌落外围区域的结构。