Browsing by Author "Shoja, Valia"

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    A Broad Analysis of Tandemly Arrayed Genes in the Genomes of Human, Mouse, and Rat
    Shoja, Valia (Virginia Tech, 2006-11-10)
    Tandemly arrayed genes (TAG) play an important functional and physiological role in the genome. Most previous studies have focused on individual TAG families in a few species, yet a broad characterization of TAGs is not available. We identified all the TAGs in the genomes of human, chimp, mouse, and rat and performed a comprehensive analysis of TAG distribution, TAG sizes, TAG gene orientations and intergenic distances, and TAG gene functions. TAGs account for about 14-17% of all the genomic genes and nearly one third of all the duplicated genes in the four genomes, highlighting the predominant role that tandem duplication plays in gene duplication. For all species, TAG distribution is highly heterogeneous along chromosomes and some chromosomes are enriched with TAG forests while others are enriched with TAG deserts. The majority of TAGs are of size two for all genomes, similar to the previous findings in C. elegans, A. thaliana, and O. sativa, suggesting that it is a rather general phenomenon in eukaryotes. The comparison with the genome patterns shows that TAG members have a significantly higher proportion of parallel gene orientation in all species, corroborating Graham's claim that parallel orientation is the preferred form of orientation in TAGs. Moreover, TAG members with parallel orientation tend to be closer to each other than all neighboring genes with parallel orientation in the genome. The analysis of GO function indicate that genes with receptor or binding activities are significantly over-represented by TAGs. Simulation reveals that random gene rearrangements have little effect on the statistics of TAGs for all genomes. It is noteworthy to mention that gene family sizes are significantly correlated with the extent of tandem duplication, suggesting that tandem duplication is a preferred form of duplication, especially in large families. There has not been any systematic study of TAG genes' expression patterns in the genome. Taking advantage of recent large-scale microarray data, we were able to study expression divergence of some of the TAGs of size two in human and mouse for which the expression data is available and examine the effect of sequence divergence, gene orientation, and physical proximity on the divergence of gene expression patterns. Our results show that there is a weak negative correlation between sequence divergence and expression similarity between the two members of a TAG, and also a weak negative correlation between physical proximity of two genes and their expression similarity. No significant relationship was detected between gene orientation and expression similarity. Moreover, we compared the expression breadth of upstream and downstream duplicate copies and found that downstream duplicate does not show significantly narrower expression breadth. We also compared TAG gene pairs with their neighboring non-TAG pairs for both physical proximity and expression similarity. Our results show that TAG gene pairs do not show any distinct differences in the two aspects from their neighboring gene pairs, suggesting that sufficient divergence has occurred to these duplicated genes during evolution and their original similarity conferred by duplication has decayed to a level that is comparable to their surrounding regions.
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    Expression Divergence of Tandemly Arrayed Genes in Human and Mouse
    Shoja, Valia; Murali, T. M.; Zhang, Liqing (Hindawi, 2007-10-30)
    Tandemly arrayed genes (TAGs) account for about one third of the duplicated genes in eukaryotic genomes, yet there has not been any systematic study of their gene expression patterns. Taking advantage of recently published large-scale microarray data sets, we studied the expression divergence of 361 two-member TAGs in human and 212 two-member TAGs in mouse and examined the effect of sequence divergence, gene orientation, and chromosomal proximity on the divergence of TAG expression patterns. Our results show that there is a weak negative correlation between sequence divergence of TAG members and their expression similarity. There is also a weak negative correlation between chromosomal proximity of TAG members and their expression similarity. We did not detect any significant relationship between gene orientation and expression similarity. We also found that downstream TAG members do not show significantly narrower expression breadth than upstream members, contrary to what we predict based on TAG expression divergence hypothesis that we propose. Finally, we show that both chromosomal proximity and expression correlation in TAGs do not differ significantly from their neighboring non-TAG gene pairs, suggesting that tandem duplication is unlikely to be the cause for the higher-than-random expression association between neighboring genes on a chromosome in human and mouse.
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    H++: a server for estimating pK(a)s and adding missing hydrogens to macromolecules
    Gordon, John C.; Myers, Jonathan B.; Folta, Timothy; Shoja, Valia; Heath, Lenwood S.; Onufriev, Alexey V. (2005-07-01)
    The structure and function of macromolecules depend critically on the ionization (protonation) states of their acidic and basic groups. A number of existing practical methods predict protonation equilibrium pK constants of macromolecules based upon their atomic resolution Protein Data Bank (PDB) structures; the calculations are often performed within the framework of the continuum electrostatics model. Unfortunately, these methodologies are complex, involve multiple steps and require considerable investment of effort. Our web server http://biophysics.cs.vt.edu/H++ provides access to a tool that automates this process, allowing both experts and novices to quickly obtain estimates of pKs as well as other related characteristics of biomolecules such as isoelectric points, titration curves and energies of protonation microstates. Protons are added to the input structure according to the calculated ionization states of its titratable groups at the user-specified pH; the output is in the PQR (PDB + charges + radii) format. In addition, corresponding coordinate and topology files are generated in the format supported by the molecular modeling package AMBER. The server is intended for a broad community of biochemists, molecular modelers, structural biologists and drug designers; it can also be used as an educational tool in biochemistry courses.