Browsing by Author "Lin, Zhenguo"

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    Computational Analysis of Gene Duplication and Network Evolution
    (2014-04-25) Zhu, Yun; Nakhleh, Luay K.; Kavraki, Lydia E.; Kohn, Michael H.; Lin, Zhenguo
    Molecular interaction networks have emerged as a powerful data source for answering a plethora of biological questions ranging from how cells make decisions to how species evolve. The availability of such data from multiple organisms allows for their analysis from an evolutionary perspective. Gene duplication plays an important role in the evolution of genomes and interactomes, and elucidating the interplay between how genomes and interactomes evolve in light of gene duplication is of great interest. In order to achieve this goal, it is important to develop models and algorithms for analyzing network evolution, particularly with respect to gene duplication events. The contributions of my thesis are four-fold. First, I developed a new genotype model that combines genomes with regulatory network, and a population genetic framework for simulating the evolution of this genotype. Using the simulator, I established explanations for gene duplicability. Second, I developed novel algorithms for probabilistic inference of ancestral networks from extant taxa, in a phylogenetic setup. Third, I conducted data analyses focusing on whole-genome duplication in yeast, and established a rate of protein-protein interaction networks, and devised a method for generating hypotheses about gene duplicate fates from network data. Fourth, and not least, I investigated the role of networks in defining adaptive models for gene duplication. In summary, my thesis contributes new analytical tools and data analyses that help elucidate and understand the interplay between gene duplication at the genomic and interactomic levels.
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    Evolution After Whole-genome Duplication: A Network Perspective
    (Genetics Society of America, 2013) Zhu, Yun; Lin, Zhenguo; Nakhleh, Luay
    Gene duplication plays an important role in the evolution of genomes and interactomes. Elucidating how evolution after gene duplication interplays at the sequence and network level is of great interest. In this paper, we analyze a data set of gene pairs that arose through whole-genome duplication (WGD) in yeast. All these pairs have the same duplication time, making them ideal for evolutionary investigation. We investigated the interplay between evolution after WGD at the sequence and network levels, and correlated these two levels of divergence with gene expression and tness data. We nd that molecular interactions involving WGD genes evolve at rates that are three orders of magnitude slower than the rates of evolution of the corresponding sequences. Further, we nd that divergence of WGD pairs correlates strongly with gene expression and tness data. Owing to the role of gene duplication in determining redundancy in biological systems and particularly at the network level, we investigated the role of interaction networks in elucidating the evolutionary fate of duplicated genes. We nd that gene neighborhoods in interaction networks provide a mechanism for inferring these fates, and we developed an algorithm for achieving this task. Further epistasis analysis of WGD pairs categorized by their inferred evolutionary fates demonstrated the utility of these techniques. Finally, we nd that WGD pairs and other pairs of paralogous genes of small-scale duplication origin share similar properties, giving good support for generalizing our results from WGD pairs to evolution after gene duplication in general.
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    EVOLUTION OF GENOME ORGANIZATION IN ANIMALS AND YEASTS
    (2015-09-01) Lv, Jie; Nakhleh, Luay K.; Kohn, Michael H.; Shamoo, Yousif; Lin, Zhenguo
    This dissertation focus on one fundamental question: Does it matter where a gene reside on a chromosome? To answer this question, we further asked two questions that are more lineage-specific: Could the large-scale patterns of genome organization across animal species give us new insights to the underling mechanisms of genome evolution? Is there any kind of universal evolutionary patterns of genome organization among yeasts? To answer the first question, we developed a simple model of genome evolution that can explain conservation of macrosynteny (chromosome-scale gene linkage relationships) across diverse metazoan species. Many metazoan genomes preserve macrosynteny from the common ancestor of multi-cellular animal life, but the evolutionary mechanism responsible for this conservation is still unknown. We show that a simple model of genome evolution, in which Double Cut and Join (DCJ) moves are allowed only if they maintain chromosomal linkage among a set of constrained genes, can simultaneously account for the level of macrosynteny conservation observed from pair wise genome comparison and for correlated conservation among multiple species. Results from biological correlation tests prove dosage-sensitive genes are good candidates for these constrained genes and thus suggest that constraints on gene dosage may have acted over long evolutionary timescales to constrain chromosomal reorganization in metazoan genomes. For the second question, we found that fission yeasts show highly conserved genome architecture, compared to budding yeasts. Despite similar rates of sequence divergence, both gene contents and genome organizations are much more conserved in fission yeasts than in budding yeasts. The rate of gene order divergence in fission yeasts is about four times slower than that of budding yeasts. Also, comparing to budding yeasts, gene duplication events among fission yeasts are more synchronized, mainly limited to fewer function categories and significantly enriched in the subtelomeric regions of chromosomes. These results suggested that highly conserved genome organization and lack of gene content innovation might play important roles in constraining the species diversification within fission yeasts. This dissertation established an innovative computational framework for efficiently developing models of genome evolution based on observed patterns from real genome comparisons. Also, it revealed comprehensive evolutionary patterns of genome organization across yeast species and provided insights into the relative importance of point mutations and large-scale genetic rearrangements as sources of functional innovations and biodiversity.
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    Heterogeneous rates of genome rearrangement contributed to the disparity of species richness in Ascomycota
    (BioMed Central, 4/24/2018) Rajeh, Ahmad; Lv, Jie; Lin, Zhenguo
    Abstract Background Chromosomal rearrangements have been shown to facilitate speciation through creating a barrier of gene flow. However, it is not known whether heterogeneous rates of chromosomal rearrangement at the genome scale contributed to the huge disparity of species richness among different groups of organisms, which is one of the most remarkable and pervasive patterns on Earth. The largest fungal phylum Ascomycota is an ideal study system to address this question because it comprises three subphyla (Saccharomycotina, Taphrinomycotina, and Pezizomycotina) whose species numbers differ by two orders of magnitude (59,000, 1000, and 150 respectively). Results We quantified rates of genome rearrangement for 71 Ascomycota species that have well-assembled genomes. The rates of inter-species genome rearrangement, which were inferred based on the divergence rates of gene order, are positively correlated with species richness at both ranks of subphylum and class in Ascomycota. This finding is further supported by our quantification of intra-species rearrangement rates based on paired-end genome sequencing data of 216 strains from three representative species, suggesting a difference of intrinsic genome instability among Ascomycota lineages. Our data also show that different rates of imbalanced rearrangements, such as deletions, are a major contributor to the heterogenous rearrangement rates. Conclusions Various lines of evidence in this study support that a higher rate of rearrangement at the genome scale might have accelerated the speciation process and increased species richness during the evolution of Ascomycota species. Our findings provide a plausible explanation for the species disparity among Ascomycota lineages, which will be valuable to unravel the underlying causes for the huge disparity of species richness in various taxonomic groups.