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Faisal Nouroz,Shumaila Noreen,J. S. Heslop-Harrison 한국유전학회 2015 Genes & Genomics Vol.37 No.11
Transposons, the mobile genetics elements played an important role in genome evolution and duplication. Several DNA transposons superfamilies are described in plants and animal genomes; CACTA, hAT, Mariner Mutator and Harbinger being the most diverse among plants. The hAT transposons are proliferating in many plant and animal species. The dot plot comparison, computational and molecular approaches were used for the characterization and diversification of non-autonomous hAT families in Brassica and 494 and 30 full length elements were collected with estimated copies of *5052 and *4110 from whole Brassica rapa and Brassica oleracea genomes respectively. The analysis of terminal inverted repeats (TIRs) of these hAT sequences classified them into 13 families on the basis of TIRs sequence similarities. The WebLogo of TIRs of hATs confirmed that few family based TIRs are highly conserved, while other showed variable nucleotide sequences. Transposons based sequence specific amplification polymorphism markers revealed the insertion preference of hATs in diverse Brassica genomes and found many elements as polymorphic across Brassica accessions. Some elements were A or C-genome specific, while most of them are present in Brassica diploids and allopolyploids revealing their presence before separation of A, B and C-Brassica genomes around 8 MYA. Several other unknown mobile insertions were identified with or without TIRs and TSDs of varied lengths, not common to known transposon superfamilies. The detailed study of these insertions revealed their distribution and mobile nature, which although less in numbers and small in sizes are playing a role in genome evolution.
Analysis and extension of a biochemical network model using robust control theory
Kim, J.-S.,Valeyev, N. V.,Postlethwaite, I.,Heslop-Harrison, P.,Cho, K.-H.,Bates, D. G. John Wiley Sons, Ltd. 2010 INTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONT Vol.20 No.9
<P>Mathematical models of biological processes which have been observed in vivo to be highly robust to intracellular and environmental variations should themselves display appropriate levels of robustness when analysed in silico. This paper uses techniques from robust control theory to analyse and extend a mathematical model of the interacting proteins underlying adenosine 3′, 5′-cyclic monophosphate (cAMP) oscillations in aggregating Dictyostelium cells. Starting with a previously proposed ‘minimal’ model, we show how robustness analysis using the structured singular value can identify points of structural fragility in the network. By combining these results with insights from recent results from the experimental literature, we show how the original model can be augmented with some important additional modules, comprising networks involving IP<SUB>3</SUB> and Ca<SUP>2+</SUP>. By analysing the robustness of our new extended model, we are able to show that dynamic interactions between the different modules play a pivotal role in generating robust cAMP oscillations; thus, significantly improving our understanding of the design principles underlying this complex biological system. Copyright © 2009 John Wiley & Sons, Ltd.</P>
Reduction of Complex Signaling Networks to a Representative Kernel
Kim, J.-R.,Kim, J.,Kwon, Y.-K.,Lee, H.-Y.,Heslop-Harrison, P.,Cho, K.-H. American Association for the Advancement of Scienc 2011 Science signaling Vol.4 No.175
<P>The network of biomolecular interactions that occurs within cells is large and complex. When such a network is analyzed, it can be helpful to reduce the complexity of the network to a 'kernel' that maintains the essential regulatory functions for the output under consideration. We developed an algorithm to identify such a kernel and showed that the resultant kernel preserves the network dynamics. Using an integrated network of all of the human signaling pathways retrieved from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, we identified this network's kernel and compared the properties of the kernel to those of the original network. We found that the percentage of essential genes to the genes encoding nodes outside of the kernel was about 10%, whereas similar to 32% of the genes encoding nodes within the kernel were essential. In addition, we found that 95% of the kernel nodes corresponded to Mendelian disease genes and that 93% of synthetic lethal pairs associated with the network were contained in the kernel. Genes corresponding to nodes in the kernel had low evolutionary rates, were ubiquitously expressed in various tissues, and were well conserved between species. Furthermore, kernel genes included many drug targets, suggesting that other kernel nodes may be potential drug targets. Owing to the simplification of the entire network, the efficient modeling of a large-scale signaling network and an understanding of the core structure within a complex framework become possible.</P>
Kim, Junil,Kim, Tae-Geon,Jung, Sung Hoon,Kim, Jeong-Rae,Park, Taesung,Heslop-Harrison, Pat,Cho, Kwang-Hyun Oxford University Press 2008 Bioinformatics Vol.24 No.13
<P>MOTIVATION: Gene regulatory networks (GRNs) govern cellular differentiation processes and enable construction of multicellular organisms from single cells. Although such networks are complex, there must be evolutionary design principles that shape the network to its present form, gaining complexity from simple modules. RESULTS: To isolate particular design principles, we have computationally evolved random regulatory networks with a preference to result either in hysteresis (switching threshold depending on current state), or in multistationarity (having multiple steady states), two commonly observed dynamical features of GRNs related to differentiation processes. We have analyzed the resulting evolved networks and compared their structures and characteristics with real GRNs reported from experiments. Conclusion: We found that the artificially evolved networks have particular topologies and it was notable that these topologies share important features and similarities with the real GRNs, particularly in contrasting properties of positive and negative feedback loops. We conclude that the structures of real GRNs are consistent with selection to favor one or other of the dynamical features of multistationarity or hysteresis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.</P>
Genome Constitution and Classification Using Retrotransposon-Based Markers in the Orphan Crop Banana
( Chee How Teo ),( Siang Hee Tan ),( Chai Ling Ho ),( Qamaruz Zaman Faridah ),( Yasmin Rofina Othman ),( John Seymour Heslop Harrison ),( Ruslan Kalendar ),( Alan Howard Schulman ) 한국식물학회 2005 Journal of Plant Biology Vol.48 No.1
We have exploited the repetitive and dispersed nature of many long terminal repeat (LTR)-retrotransposon families for characterizing genome constitutions and classifying cultivars of the genus Musa. Insertional polymorphisms of the elements were studied using seven published and two newly designed primers facing outwards from the LTRs and reverse transcriptase (RT) domain of the retrotransposon. The primers generated specific amplification patterns showing the universal applicability of this marker type. The Inter-Retrotransposon Amplified Polymorphism (IRAP) markers distinguished the A and B genomes of the banana species (Musa acuminata Colla and Musa balbisiana Colla) and between banana cultivars. The IRAP markers enabled phylogenetic analysis of 16 Malaysian banana cultivars and determination of the genome constitution of hybrid banana (AAB, ABB, AABB, and AAAB), and gave information about ancestral genotypes of the hybrids. In addition, the TRAP detected new retrotransposon insertions into the genome of tissue culture regenerants. This PCR-based IRAP assay is amenable to large-scale throughput demands in screening breeding populations and is applicable for any crop.