Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny

During the last decade, a variety of critical biological processes, including early embryo development, cell proliferation, differentiation, apoptosis, and metabolic regularity, have been shown to be genetically regulated by a large gene family encoding a class of tiny RNA molecules termed microRNAs (miRNAs). All miRNAs share a common biosynthetic pathway and reaction mechanisms. The sequence of many miRNAs is found to be conserved, in their mature form, among different organisms. In addition, the evolutionary appearance of multicellular organisms appears to correlate with the appearance of the miRNA pathway for regulating gene expression. The miRNA pathway has the potential to regulate vast networks of gene products in a coordinate manner. Recent evidence has not only implicated the miRNA pathway in regulating a vast array of basic cellular processes but also specialized processes that are required for cellular identity and tissue specificity. A survey of the literature shows that some miRNA pathways are conserved virtually intact throughout phylogeny while miRNA diversity also correlates with speciation. The number of miRNA genes, the expression of miRNAs, and target diversities of miRNAs tend to be positively correlated with morphological complexities observed in animals. Thus, organismal complexity can be estimated by the complexity of the miRNA circuitry. The complexity of the miRNA gene families establishes a link between genotypic complexity and phenotypic complexity in animal evolution. In this paper, we start with the discussion of miRNA conservation. Then we interpret the trends in miRNA conservation to deduce miRNA evolutionary trends in metazoans. Based on these conservation patterns observed in each component of the miRNA regulatory system, we attempt to propose a global insight on the probable consistency between morphological evolution in animals and the molecular evolution of miRNA gene activity in the cell.     

Circadian rhythms from multiple oscillators: lessons from diverse organisms

The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity.     

The evolutionary context of robust and redundant cell biological mechanisms

The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently redundant mechanisms over evolutionary time may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses.     

Evolution of living organisms as a multilevel process

There is inherent capacity to increase the degree of aggregation within each of the levels of structural organization of living matter. At the macromolecular level (MML), this is an increase in the gene number in the genomes of evolving organisms; at the cellular level (CL), an increase in cell size; and at the multicellular level (MCL), an increase in the number of cells in the multicellular aggregate. However, the increase in the degree of aggregation causes gene incompatibility in case of genome evolution and instability in case of large cells and multicellular aggregates with simple structure. Gene incompatibility may be neutralized by spacio-temporal disconnection of the products of incompatible genes at the cellular and multicellular levels. The larger cells and multicellular aggregates are stabilized by increased structural complexity which is a consequence of the origin of new genes. There is a feedback between the processes of evolution at different levels MML→CL→ MCL.The processes of evolutionary development at different levels of structural organization are also relatively independent. The coincidence of these processes gives rise to stable organisms of higher complexity, which are then subjected to natural selection and population processes to establish a new step in progressive biological evolution. In all of the normal organisms of newly evolved species there is a correspondence between the different levels of structural organization, i.e. in their degree of aggregation, their complexity and functional organization. The form of correspondence for multicellular organisms is presented.     

Bacterial quorum sensing: circuits and applications

Bacterial quorum sensing (QS) systems are cell density—dependent regulatory networks that coordinate bacterial behavioural changes from single cellular organisms at low cell densities to multicellular types when their population density reaches a threshold level. At this stage, bacteria produce and perceive small diffusible signal molecules, termed autoinducers in order to mediate gene expression. This often results in phenotypic shifts, like planktonic to biofilm or non-virulent to virulent. In this way, they regulate varied physiological processes by adjusting gene expression in concert with their population size. In this review we give a synopsis of QS mediated cell–cell communication in bacteria. The first part focuses on QS circuits of some Gram-negative and Gram-positive bacteria. Thereafter, attention is drawn on the recent applications of QS in development of synthetic biology modules, for studying the principles of pattern formation, engineering bi-directional communication system and building artificial communication networks. Further, the role of QS in solving the problem of biofouling is also discussed.     

以发育模块重复征用和整合为基础的进化创新机制

进化新征的起源和分化是进化发育生物学研究的核心问题。通过对多细胞生物早期发育调控机制的比较分析,发现亲缘关系较远的生物所共有的一些形态特征受保守的发育调控程序调节（深同源性）。许多创新性状的发生是基于对预先存在的基因或发育调控模块的重复利用和整合。发育基因调控网络在结构和功能上高度模块化,因此不仅可以通过模块拆分和重复征用改变发育程式,而且也增强了调控网络自身的进化力。研究基因调控网络和发育系统的进化动态将有助于更深入地认识生物演化过程中创新性状发生和表型进化的分子机制。     

A data-driven integrative model of sepal primordium polarity in Arabidopsis

Flower patterning is determined by a complex molecular network but how this network functions remains to be elucidated. Here, we develop an integrative modeling approach that assembles heterogeneous data into a biologically coherent model to allow predictions to be made and inconsistencies among the data to be found. We use this approach to study the network underlying sepal development in the young flower of Arabidopsis thaliana. We constructed a digital atlas of gene expression and used it to build a dynamical molecular regulatory network model of sepal primordium development. This led to the construction of a coherent molecular network model for lateral organ polarity that fully recapitulates expression and interaction data. Our model predicts the existence of three novel pathways involving the HD-ZIP III genes and both cytokinin and ARGONAUTE family members. In addition, our model provides predictions on molecular interactions. In a broader context, this approach allows the extraction of biological knowledge from diverse types of data and can be used to study developmental processes in any multicellular organism.     

Biological consequences of dosage dependent gene regulatory systems

Chromatin and gene regulatory molecules tend to operate in multisubunit complexes in the process of controlling gene expression. Accumulating evidence suggests that varying the amount of any one member of such complexes will affect the function of the whole via the kinetics of assembly and other actions. In effect, they exhibit a "balance" among themselves in terms of the activity of the whole. When this fact is coupled with genetic and biological observations stretching back a century, a synthesis emerges that helps explain at least some aspects of a variety of phenomena including aneuploid syndromes, dosage compensation, quantitative trait genetics, regulatory gene evolution following polyploidization, the emergence of complexity in multicellular organisms, the genetic basis of evolutionary gradualism and potential implications for heterosis and co-evolving genes complexes involved with speciation. In this article we will summarize the evidence for this potential synthesis.     

Structure, function and evolution of microbial adenylyl and guanylyl cyclases

Cells respond to signals of both environmental and biological origin. Responses are often receptor mediated and result in the synthesis of so-called second messengers that then provide a link between extracellular signals and downstream events, including changes in gene expression. Cyclic nucleotides (cAMP and cGMP) are among the most widely studied of this class of molecule. Research on their function and mode of action has been a paradigm for signal transduction systems and has shaped our understanding of this important area of biology. Cyclic nucleotides have diverse regulatory roles in both unicellular and multicellular organisms, highlighting the utility and success of this system of molecular communication. This review will examine the structural diversity of microbial adenylyl and guanylyl cyclases, the enzymes that synthesize cAMP and cGMP respectively. We will address the relationship of structure to biological function and speculate on the complex origin of these crucial regulatory molecules. A review is timely because the explosion of data from the various genome projects is providing new and exciting insights into protein function and evolution.     

Targeting secret handshakes of biological processes for novel drug development

In multicellular organisms, several biological processes control the rise and fall of life. Different cell types communicate and co-operate in response to different stimulus through cell to cell signaling and regulate biologic processes in the cell/organism. Signaling in multicellular organism has to be made very secretly so that only the target cell responds to the signal. Of all the biomolecules, nature chose mainly proteins for secret delivery of information both inside and outside the cell. During cell signaling, proteins physically interact and shake hands for transfer of secret information by a phenomenon called as protein–protein interactions (PPIs). In both, extra and intracellular signaling processes PPIs play a crucial role. PPIs involved in cellular signaling are the primary cause for cell proliferation, differentiation, movement, metabolism, death and various other biological processes not mentioned here. These secret handshakes are very specific for specific functions. Any alterations/malfunctions in particular PPIs results in diseased condition. An overview of signaling pathways and importance of PPIs in cellular function and possibilities of targeting PPIs for novel drug development are discussed in this review.     

The key to development: interpreting the histone code?

Developmental stages in multicellular organisms proceed according to a temporally and spatially precise pattern of gene expression. It has become evident that changes within the chromatin structure brought about by covalent modifications of histones are of crucial importance in determining many biological processes, including development. Numerous studies have provided evidence that the enzymes responsible for the modifications of histones function in a coordinated pattern to control gene expression in the short term and, through the transferral of these modifications by inheritance to their progeny, in the long term.     

Engineering and control of biological systems: A new way to tackle complex diseases

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health.