Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Curr Biol. 2011 Jul 12;21(13):1092-101. doi: 10.1016/j.cub.2011.05.040. Epub 2011 Jun 16.
Complex regulatory circuits in biology are often built of simpler subcircuits or modules. In most cases, the functional consequences and evolutionary origins of modularity remain poorly defined.
Here, by combining single-cell microscopy with genetic approaches, we demonstrate that two separable modules independently govern the temporal and spatial control of DNA replication in the asymmetrically dividing bacterium Caulobacter crescentus. DNA replication control involves DnaA, which promotes initiation, and CtrA, which silences initiation. We show that oscillations in DnaA activity dictate the periodicity of replication while CtrA governs the asymmetric replicative fates of daughter cells. Importantly, we demonstrate that DnaA activity oscillates independently of CtrA.
The genetic separability of spatial and temporal control modules in Caulobacter reflects their evolutionary history. DnaA is the central component of an ancient and phylogenetically widespread circuit that governs replication periodicity in Caulobacter and most other bacteria. By contrast, CtrA, which is found only in the asymmetrically dividing α-proteobacteria, was integrated later in evolution to enforce replicative asymmetry on daughter cells.
生物学中的复杂调控回路通常由更简单的子回路或模块构建而成。在大多数情况下，模块性的功能后果和进化起源仍未得到明确界定。
在这里，我们通过结合单细胞显微镜和遗传方法，证明了两个可分离的模块独立控制着不对称分裂细菌新月柄杆菌中 DNA 复制的时空控制。DNA 复制控制涉及促进起始的 DnaA 和沉默起始的 CtrA。我们表明，DnaA 活性的振荡决定了复制的周期性，而 CtrA 则决定了子细胞的不对称复制命运。重要的是，我们证明了 DnaA 活性的振荡独立于 CtrA。
新月柄杆菌中时空控制模块的遗传可分离性反映了它们的进化历史。DnaA 是一个古老且在系统发育上广泛分布的调控复制周期性的电路的核心组件，该电路在新月柄杆菌和大多数其他细菌中起作用。相比之下，仅在不对称分裂的α变形菌中发现的 CtrA 是在进化后期被整合进来的，以对子代细胞施加复制不对称性。
