Genetics and Genomics Commons^™

Threshold-Dependent Repression Of Spl Gene Expression By Mir156/Mir157 Controls Vegetative Phase Change In Arabidopsis Thaliana, Jia He, Mingli Xu, Matthew R. Willmann, Kevin Mccormick, Tieqiang Hu, Li Yang, Colby G. Starker, Daniel F. Voytas, Blake C. Meyers, R. Scott Poethig

Faculty Publications

Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in leaf morphology that occur during vegetative phase change, we measured their abundance in successive leaves and characterized the phenotype of mutations in different MIR156 and MIR157 genes. miR156/miR157 decline rapidly between leaf 1&2 and leaf 3 and decrease more slowly after this point. The amount of miR156/miR157 in leaves 1&2 greatly exceeds the …

Developmental Functions Of Mir156-Regulated Squamosa Promoter Binding Protein-Like (Spl) Genes In Arabidopsis Thaliana, Mingli Xu, Tieqiang Hu, Jianfei Zhao, Mee-Yeon Park, Keith W. Earley, Gang Wu, Li Yang, R. Scott Poethig

Faculty Publications

Correct developmental timing is essential for plant fitness and reproductive success. Two important transitions in shoot development—the juvenile-to-adult vegetative transition and the vegetative-to-reproductive transition—are mediated by a group of genes targeted by miR156, SQUAMOSA PROMOTER BINDING PROTEIN (SBP) genes. To determine the developmental functions of these genes in Arabidopsis thaliana, we characterized their expression patterns, and their gain-of-function and loss-of-function phenotypes. Our results reveal that SBP-LIKE (SPL) genes in Arabidopsis can be divided into three functionally distinct groups: 1) SPL2, SPL9, SPL10, SPL11, SPL13 and SPL15 contribute to both the juvenile-to-adult vegetative transition …

Multiple Roles For Hoxa3 In Regulating Thymus And Parathyroid Differentiation And Morphogenesis In Mouse, Jena L. Chojnowski, Kyoko Masuda, Heidi A. Trau, Kirk Thomas, Mario Capeechi, Nancy R. Manley

Faculty Publications

Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. …

Sugar Promotes Vegetative Phase Change In Arabidopsis Thaliana By Repressing The Expression Of Mir156a And Mir156c, Li Yang, Mingli Xu, Yeonjong Koo, Jia He, R. Scott Poethig

Faculty Publications

Nutrients shape the growth, maturation, and aging of plants and animals. In plants, the juvenile to adult transition (vegetative phase change) is initiated by a decrease in miR156. In Arabidopsis, we found that exogenous sugar decreased the abundance of miR156, whereas reduced photosynthesis increased the level of this miRNA. This effect was correlated with a change in the timing of vegetative phase change, and was primarily attributable to a change in the expression of two genes, MIR156A and MIR156C, which were found to play dominant roles in this transition. The glucose-induced repression of miR156 was dependent on the …

Parsimony And Model-Based Analyses Of Indels In Avian Nuclear Genes Reveal Congruent And Incongruent Phylogenetic Signals, Tamaki Yuri, Rebecca T. Kimball, John Harshman, Rauri C.K. Bowie, Michael J. Braun, Jena L. Chojnowski, Kin-Lan Han, Shannon J. Hackett, Christopher J. Huddleston, William S. Moore, Sushma Reddy, Frederick H. Sheldon, David W. Steadman, Christopher C. Witt, Edward L. Braun

Faculty Publications

Insertion/deletion (indel) mutations, which are represented by gaps in multiple sequence alignments, have been used to examine phylogenetic hypotheses for some time. However, most analyses combine gap data with the nucleotide sequences in which they are embedded, probably because most phylogenetic datasets include few gap characters. Here, we report analyses of 12,030 gap characters from an alignment of avian nuclear genes using maximum parsimony (MP) and a simple maximum likelihood (ML) framework. Both trees were similar, and they exhibited almost all of the strongly supported relationships in the nucleotide tree, although neither gap tree supported many relationships that have proven …

An Unbiased Approach To Identify Genes Involved In Development In A Turtle With Temperature-Dependent Sex Determination, Jena L. Chojnowski, Edward L. Braun

Faculty Publications

Many reptiles exhibit temperature-dependent sex determination (TSD). The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD) where it is determined by the presence of specific alleles (or genetic loci). We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach). We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta), a turtle with TSD. Genes with differential mRNA accumulation in response to …

Density Based Pruning For Identification Of Differentially Expressed Genes From Microarray Data, Jianjun Hu, J. Xu

Faculty Publications

Motivation

Identification of differentially expressed genes from microarray datasets is one of the most important analyses for microarray data mining. Popular algorithms such as statistical t-test rank genes based on a single statistics. The false positive rate of these methods can be improved by considering other features of differentially expressed genes.

Results

We proposed a pattern recognition strategy for identifying differentially expressed genes. Genes are mapped to a two dimension feature space composed of average difference of gene expression and average expression levels. A density based pruning algorithm (DB Pruning) is developed to screen out potential differentially expressed genes usually …

Genome3d: A Viewer-Model Framework For Integrating And Visualizing Multi-Scale Epigenomic Information Within A Three-Dimensional Genome, Thomas M. Asbury, Matt Mitman, Jijun Tang, W. Jim Zheng

Faculty Publications

Background
New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation.

Results
We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order …

Using Jackknife To Assess The Quality Of Gene Order Phylogenies, Jian Shi, Yiwei Zhang, Haiwei Luo, Jijun Tang

Faculty Publications

Background
In recent years, gene order data has attracted increasing attention from both biologists and computer scientists as a new type of data for phylogenetic analysis. If gene orders are viewed as one character with a large number of states, traditional bootstrap procedures cannot be applied. Researchers began to use a jackknife resampling method to assess the quality of gene order phylogenies.

Results
In this paper, we design and conduct a set of experiments to validate the performance of this jackknife procedure and provide discussions on how to conduct it properly. Our results show that jackknife is very useful to …

Gene Order Phylogeny And The Evolution Of Methanogens, Haiwei Luo, Zhiyi Sun, William Arndt, Jian Shi, Robert Friedman, Jijun Tang

Faculty Publications

Methanogens are a phylogenetically diverse group belonging to Euryarchaeota. Previously, phylogenetic approaches using large datasets revealed that methanogens can be grouped into two classes, “Class I” and “Class II”. However, some deep relationships were not resolved. For instance, the monophyly of “Class I” methanogens, which consist of Methanopyrales, Methanobacteriales and Methanococcales, is disputable due to weak statistical support. In this study, we use MSOAR to identify common orthologous genes from eight methanogen species and a Thermococcale species (outgroup), and apply GRAPPA and FastME to compute distance-based gene order phylogeny. The gene order phylogeny supports two classes of methanogens, but it …

Gene Order Phylogeny Of The Genus Prochlorococcus, Haiwei Luo, Jian Shi, William Arndt, Jijun Tang, Robert Friedman

Faculty Publications

Background
Using gene order as a phylogenetic character has the potential to resolve previously unresolved species relationships. This character was used to resolve the evolutionary history within the genus Prochlorococcus, a group of marine cyanobacteria.

Methodology/Principal Findings
Orthologous gene sets and their genomic positions were identified from 12 species of Prochlorococcus and 1 outgroup species of Synechococcus. From this data, inversion and breakpoint distance-based phylogenetic trees were computed by GRAPPA and FastME. Statistical support of the resulting topology was obtained by application of a 50% jackknife resampling technique. The result was consistent and congruent with nucleotide sequence-based and gene-content based …

Improving Reversal Median Computation Using Commuting Reversals And Cycle Information, William Arndt, Jijun Tang

Faculty Publications

In the past decade, genome rearrangements have attracted increasing attention from both biologists and computer scientists as a new type of data for phylogenetic analysis. Methods for reconstructing phylogeny from genome rearrangements include distance-based methods, MCMC methods, and direct optimization methods. The latter, pioneered by Sankoff and extended with the software suites GRAPPA and MGR, is the most accurate approach, but is very limited due to the difficulty of its scoring procedure—it must solve multiple instances of the reversal median problem to compute the score of a given tree. The reversal median problem is known to be NP-hard and all …

Multi-Break Rearrangements And Breakpoint Re-Uses: From Circular To Linear Genomes, Max A. Alekseyev

Faculty Publications

Multi-break rearrangements break a genome into multiple fragments and further glue them together in a new order. While 2-break rearrangements represent standard reversals, fusions, fissions, and translocations, 3-break rearrangements represent a natural generalization of transpositions. Alekseyev and Pevzner (2007a, 2008a) studied multi-break rearrangements in circular genomes and further applied them to the analysis of chromosomal evolution in mammalian genomes. In this paper, we extend these results to the more difficult case of linear genomes. In particular, we give lower bounds for the rearrangement distance between linear genomes and for the breakpoint re-use rate as functions of the number and proportion …

Phylogenetic Reconstruction From Transpositions, Feng Yue, Meng Zhang, Jijun Tang

Faculty Publications

Background
Because of the advent of high-throughput sequencing and the consequent reduction in the cost of sequencing, many organisms have been completely sequenced and most of their genes identified. It thus has become possible to represent whole genomes as ordered lists of gene identifiers and to study the rearrangement of these entities through computational means. As a result, genome rearrangement data has attracted increasing attentions from both biologists and computer scientists as a new type of data for phylogenetic analysis. The main events of genome rearrangements include inversions, transpositions and transversions. To date, GRAPPA and MGR are the most accurate …

Gene Rearrangement Analysis And Ancestral Order Inference From Chloroplast Genomes With Inverted Repeat, Feng Yue, Liying Cui, Claude W. Depamphilis, Bernard M.E. Moret, Jijun Tang

Faculty Publications

Background
Genome evolution is shaped not only by nucleotide substitutions, but also by structural changes including gene and genome duplications, insertions, deletions and gene order rearrangements. The most popular methods for reconstructing phylogeny from genome rearrangements include GRAPPA and MGR. However these methods are limited to cases where equal gene content or few deletions can be assumed. Since conserved duplicated regions are present in many chloroplast genomes, the inference of inverted repeats is needed in chloroplast phylogeny analysis and ancestral genome reconstruction.

Results
We extend GRAPPA and develop a new method GRAPPA-IR to handle chloroplast genomes. A test of GRAPPA-IR …

Are There Rearrangement Hotspots In The Human Genome?, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

In a landmark paper, Nadeau and Taylor [18] formulated the random breakage model (RBM) of chromosome evolution that postulates that there are no rearrangement hotspots in the human genome. In the next two decades, numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introduced the fragile breakage model (FBM), postulating that the human genome is a mosaic of solid regions (with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal …

Whole Genome Duplications And Contracted Breakpoint Graphs, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

The genome halving problem, motivated by the whole genome duplication events in molecular evolution, was solved by El-Mabrouk and Sankoff in the pioneering paper [SIAM J. Comput., 32 (2003), pp. 754–792]. The El-Mabrouk–Sankoff algorithm is rather complex, inspiring a quest for a simpler solution. An alternative approach to the genome halving problem based on the notion of the contracted breakpoint graph was recently proposed in [M. A. Alekseyev and P. A. Pevzner, IEEE/ACM Trans. Comput. Biol. Bioinformatics, 4 (2007), pp. 98–107]. This new technique reveals that while the El-Mabrouk–Sankoff result is correct in most cases, it does not hold in …

Colored De Bruijn Graphs And The Genome Halving Problem, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

Breakpoint graph analysis is a key algorithmic technique in studies of genome rearrangements. However, breakpoint graphs are defined only for genomes without duplicated genes, thus limiting their applications in rearrangement analysis. We discuss a connection between the breakpoint graphs and de Bruijn graphs that leads to a generalization of the notion of breakpoint graph for genomes with duplicated genes. We further use the generalized breakpoint graphs to study the Genome Halving Problem (first introduced and solved by Nadia El-Mabrouk and David Sankoff). The El-Mabrouk-Sankoff algorithm is rather complex, and, in this paper, we present an alternative approach that is based …

Adaptive Evolution Of Chloroplast Genome Structure Inferred Using A Parametric Bootstrap Approach, Liying Cui, Jim Leebens-Mack, Li-San Wang, Jijun Tang, Linda Rymarquis, David B. Stern, Claude W. Depamphilis

Faculty Publications

Background
Genome rearrangements influence gene order and configuration of gene clusters in all genomes. Most land plant chloroplast DNAs (cpDNAs) share a highly conserved gene content and with notable exceptions, a largely co-linear gene order. Conserved gene orders may reflect a slow intrinsic rate of neutral chromosomal rearrangements, or selective constraint. It is unknown to what extent observed changes in gene order are random or adaptive. We investigate the influence of natural selection on gene order in association with increased rate of chromosomal rearrangement. We use a novel parametric bootstrap approach to test if directional selection is responsible for the …

Sequence Alignment With Matched Sections, Jerrold R. Griggs, Philip J. Hanlon, Michael S. Waterman

Faculty Publications

In molecular biology, two finite sequences are compared by displaying one sequence written over another in an alignment. The number of alignments of two sequences is related to the Stanton-Cowan numbers. This paper gives asymptotics for the number of alignments of two sequences of length n with matching sections of size at least b.