Cell-fate determination in Myxococcus xanthus development: Network dynamics and novel predictions.

Myxococcus xanthus is a myxobacterium that exhibits aggregation and cellular differentiation during the formation of fruiting bodies. Therefore, it has become a valuable model system to study the transition to multicellularity via cell aggregation. Although there is a vast set of experimental information for the development on M. xanthus, the dynamics behind cell-fate determination in this organism's development remain unclear. We integrate the currently available evidence in a mathematical network model that allows to test the set of molecular elements and regulatory interactions that are sufficient to account for the specification of the cell types that are observed in fruiting body formation. Besides providing a dynamic mechanism for cell-fate determination in the transition to multicellular aggregates of M. xanthus, this model enables the postulation of specific mechanisms behind some experimental observations for which no explanations have been provided, as well as new regulatory interactions that can be experimentally tested. Finally, this model constitutes a formal basis on which the continuously emerging data for this system can be integrated and interpreted.

An Evo-Devo Perspective on Multicellular Development of Myxobacteria.

The transition to multicellularity, recognized as one the major transitions in evolution, has occurred independently several times. While multicellular development has been extensively studied in zygotic organisms including plant and animal groups, just a few aggregative multicellular organisms have been employed as model organisms for the study of multicellularity. Studying different evolutionary origins and modes of multicellularity enables comparative analyses that can help identifying lineage-specific aspects of multicellular evolution and generic factors and mechanisms involved in the transition to multicellularity. Among aggregative multicellular organisms, myxobacteria are a valuable system to explore the particularities that aggregation confers to the evolution of multicellularity and mechanisms shared with clonal organisms. Moreover, myxobacteria species develop fruiting bodies displaying a range of morphological diversity. In this review, we aim to synthesize diverse lines of evidence regarding myxobacteria development and discuss them in the context of Evo-Devo concepts and approaches. First, we briefly describe the developmental processes in myxobacteria, present an updated comparative analysis of the genes involved in their developmental processes and discuss these and other lines of evidence in terms of co-option and developmental system drift, two concepts key to Evo-Devo studies. Next, as has been suggested from Evo-Devo approaches, we discuss how broad comparative studies and integration of diverse genetic, physicochemical, and environmental factors into experimental and theoretical models can further our understanding of myxobacterial development, phenotypic variation, and evolution.

Distinctive expression and functional regulation of the maize (Zea mays L.) TOR kinase ortholog.

TOR (Target of rapamycin) kinase is a central component of a signal transduction pathway that regulates cellular growth in response to nutrients, mitogens and growth factors in eukaryotes. Knowledge of the TOR pathway in plants is scarce, and reports in agronomical relevant plants are lacking. Previous studies indicate that Arabidopsis thaliana TOR (AtTOR) activity is resistant to rapamycin whereas maize TOR (ZmTOR) is not, suggesting that plants might have different regulation mechanisms for this signal transduction pathway. In the present work maize ZmTOR cDNA was identified and its expression regulation was analyzed during germination on different tissues at various stages of differentiation and by the main ZmTOR regulators. Our results show that ZmTOR contains all functional domains characteristic of metazoan TOR kinase. ZmTOR expression is highly regulated during germination, a critical plant development period, but not on other tissues of contrasting physiological characteristics. Bioinformatic analyses indicated that maize FKBP12 and rapamycin form a functional structure capable of targeting the ZmTOR protein, similar to other non-plant eukaryotes, further supporting its regulation by rapamycin (in contrast with the rapamycin insensitivity of Arabidopsis thaliana) and the conservation of rapamycin regulation through plant evolution.

Functional diversification of B MADS-box homeotic regulators of flower development: Adaptive evolution in protein-protein interaction domains after major gene duplication events.

B-class MADS-box genes have been shown to be the key regulators of petal and stamen specification in several eudicot model species such as Arabidopsis thaliana, Antirrhinum majus, and Petunia hybrida. Orthologs of these genes have been found across angiosperms and gymnosperms, and it is thought that the basic regulatory function of B proteins is conserved in seed plant lineages. The evolution of B genes is characterized by numerous duplications that might represent key elements fostering the functional diversification of duplicates with a deep impact on their role in the evolution of the floral developmental program. To evaluate this, we performed a rigorous statistical analysis with B gene sequences. Using maximum likelihood and Bayesian methods, we estimated molecular substitution rates and determined the selective regimes operating at each residue of B proteins. We implemented tests that rely on phylogenetic hypotheses and codon substitution models to detect significant differences in substitution rates (DSRs) and sites under positive adaptive selection (PS) in specific lineages before and after duplication events. With these methods, we identified several protein residues fixed by PS shortly after the origin of PISTILLATA-like and APETALA3-like lineages in angiosperms and shortly after the origin of the euAP3-like lineage in core eudicots, the 2 main B gene duplications. The residues inferred to have been fixed by positive selection lie mostly within the K domain of the protein, which is key to promote heterodimerization. Additionally, we used a likelihood method that accommodates DSRs among lineages to estimate duplication dates for AP3-PI and euAP3-TM6, calibrating with data from the fossil record. The dates obtained are consistent with angiosperm origins and diversification of core eudicots. Our results strongly suggest that novel multimer formation with other MADS proteins could have been crucial for the functional divergence of B MADS-box genes. We thus propose a mechanism of functional diversification and persistence of gene duplicates by the appearance of novel multimerization capabilities after duplications. Multimer formation in different combinations of regulatory proteins can be a mechanistic basis for the origin of novel regulatory functions and a gene regulatory mechanism for the appearance of morphological innovations.

Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny.

Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants.