R-3 Repository :: Browsing by Author "Kohn, Michael H."

Browsing by Author "Kohn, Michael H."

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A VKORC1‐based SNP survey of anticoagulant rodenticide resistance in the house mouse, Norway rat and roof rat in the USA
(Wiley, 2021) Diaz, Juan C.; Kohn, Michael H.
BACKGROUND: We conducted a vitamin K epoxide reductase subcomponent 1 (Vkorc1)‐based nonsynonymous Single Nucleotide Polymorphism (nsSNP) screen with focus on the house mouse (Mus musculus domesticus), but that also considered the Norway rat (Rattus norvegicus) and roof rat (R. rattus) in the USA. RESULTS: We detected six Vkorc1 nsSNPs underlying the amino‐acid polymorphisms Ala21Thr, Trp59Leu, Ile104Val, Val118Leu, Leu128Ser and Tyr139Cys in house mice (average coverage/SNP; n = 182 individuals), two nsSNPs underlying Arg35Pro and Gly46Ser in the Norway rat (n = 93), with the notable absence of Tyr139Cys (n = 179), and one nsSNP underlying Tyr25Phe in the roof rat (n = 27). Inferred resistance frequency is 29.1% for mice (variability of states 0–98.8%), 6.5% (0–33.3%) for the Norway rat, and 39.3% (0–52.6%) for the roof rat based on Tyr25Phe frequencies. CONCLUSIONS: Resistance detected in the USA in the 1980s likely was the consequence of Vkorc1 mutations in mice (Leu128Ser and Tyr139Cys), Norway rats (Arg35Pro) and roof rats (Tyr25Phe). Patterns of variant sharing between the USA and Europe indicate the importance of convergent evolution and gene flow in spreading resistance. The spread of nsSNPs in mice between continents appears to have been more effective than in Norway rats. We hypothesize that Arg35Pro may have originated in Norway rats in the USA, whereas Tyr139Cys variants originated in Europe. Tyr25Phe is the likely cause for resistance in roof rats. Further genetic testing in the USA is required to close sampling gaps, and population genomic data are needed to study the origin and spread of this adaptive trait.
Comparative Genomics of Cephalochordates
(2015-04-23) Yue, Jiaxing; Kohn, Michael H.; Nakhleh, Luay K.; Shamoo, Yousif; Guerra, Rudy; Putnam, Nicholas H.
Cephalochordates, commonly known as lancelets or amphioxus, represent an ancient chordate lineage falling at the boundary between invertebrates and vertebrates. They are considered the best living proxy for the common ancestor of all chordate animals and hold the key for understanding chordate evolution. Despite such great importance, current studies on cephalochordates are generally limited to the Branchiostoma genus, leaving the other two genera, Asymmetron and Epigonichthys largely unexplored. In this dissertation, I set out to fill this gap by developing an array of genomic resources for the Bahama cephalochordate, Asymmetron lucayanum, by both RNA-Seq and whole-genome shotgun (WGS) sequencing. The transcriptome and genome of this representative cephalochordate species were assembled and characterized via the state-of-arts comparative genomics approach. By comparing its transcriptome and genome sequences with those of a distant related cephalochordate species, Branchiostoma floridae, as well as with several representative vertebrate species, many aspects of their genome biology were illuminated, which includes lineage-specific molecular evolution rate, fast-evolving genes, evolution time frame, conserved non-coding elements, and germline-related genes. The raw genomic resources, technical pipelines and biological results and insights generated by this dissertation work will benefit the whole cephalochordate research community by providing a powerful guide for formulating new hypotheses and designing new experiments towards a better understanding about the biology and evolution of cephalochordates, as well as the evolutionary transition from invertebrates to vertebrates.
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.
Effects of Gene Interactions on Polymorphism and Divergence
(2014-05-20) Shih, Ching-Hua; Kohn, Michael H.; Nakhleh, Luay K.; Putnam, Nicholas H.; Kimmel, Marek
Patterns of interactions could influence the biological systems at various levels and potentially affect the evolutionary history. Gene interactions could affect the relation among genotypes and their phenotypes. Polymorphisms of genes potentially alter interactions among genes, and hence, affect the fitness of individuals. Certain combinations of polymorphisms among genes can be maintained by selection. The main question of this thesis regards the effects of interactions in biological systems. Reproductive isolation arises as a by-product of different combinations of substitutions between divergent populations. Bateson-Dobzhansky-Muller (BDM) model states fitness changes due to incompatible combinations of loci. Nonlinear rates of accumulation of incompatibilities have been proposed considering interactions among multiple loci. However, the effects of topologies of gene interaction networks (GINs) altering the rates of accumulation of incompatibilities have not been investigated. The third topic revolves around effects of gene interactions in hybridizing species. Gene flow homogenizes the gene pool of incipient species and impedes divergence. This process can take place because incipient species either remain in spatial contact or have secondary contact through range shifts. The porous intrinsic reproductive barriers between species for loci post various properties contributing to success to move between species. We utilized human GINs combined with single nucleotide polymorphisms (SNPs) from human HapMap to investigate the correlations between interactions and interlocus nonrandom associations of polymorphisms. To investigate the effects of gene interactions between species, we modified the “snowball effect” and simulated the rates of accumulation of incompatibilities by introducing the structure information of GINs. To profile the functional characteristics of introgressed genes, we adopted the maximum likelihood method for public genomic resources focusing on a primate hybrid zone of cynomolgus monkey (Macaca fascicularis) and rhesus monkey (M. mulatta). Our results suggest that GINs enable global scale studies and provide polygenic insight of complex traits between and within species. Application of gene interactions ranges from enhancement of genome-wide association studies, identification of interacting polymorphisms to biomedical researches. Gene interactions also provide a platform of understanding hybridization and the dynamics of speciation.
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.
An HMM-Based Comparative Genomic Framework for Detecting Introgression in Eukaryotes
(Public Library of Science, 2014) Liu, Kevin J.; Dai, Jingxuan; Truong, Kathy; Song, Ying; Kohn, Michael H.; Nakhleh, Luay
One outcome of interspecific hybridization and subsequent effects of evolutionary forces is introgression, which is the integration of genetic material from one species into the genome of an individual in another species. The evolution of several groups of eukaryotic species has involved hybridization, and cases of adaptation through introgression have been already established. In this work, we report on PhyloNet-HMM?a new comparative genomic framework for detecting introgression in genomes. PhyloNet-HMM combines phylogenetic networks with hidden Markov models (HMMs) to simultaneously capture the (potentially reticulate) evolutionary history of the genomes and dependencies within genomes. A novel aspect of our work is that it also accounts for incomplete lineage sorting and dependence across loci. Application of our model to variation data from chromosome 7 in the mouse (Mus musculus domesticus) genome detected a recently reported adaptive introgression event involving the rodent poison resistance gene Vkorc1, in addition to other newly detected introgressed genomic regions. Based on our analysis, it is estimated that about 9% of all sites within chromosome 7 are of introgressive origin (these cover about 13 Mbp of chromosome 7, and over 300 genes). Further, our model detected no introgression in a negative control data set. We also found that our model accurately detected introgression and other evolutionary processes from synthetic data sets simulated under the coalescent model with recombination, isolation, and migration. Our work provides a powerful framework for systematic analysis of introgression while simultaneously accounting for dependence across sites, point mutations, recombination, and ancestral polymorphism.
Mitochondrial DNA Phylogeography of the Norway Rat
(Public Library of Science, 2014) Song, Ying; Lan, Zhenjiang; Kohn, Michael H.
Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus) have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as, 1.2-1.6 million years ago (Mya), molecular analyses yielded, 0.5-2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China, 1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance.
Models and Methods for Evolutionary Histories Involving Hybridization and Incomplete Lineage Sorting
(2014-04-09) Yu, Yun; Nakhleh, Luay K.; Jermaine, Christopher M.; Kohn, Michael H.; Kavraki, Lydia E.
Hybridization plays an important evolutionary role in several groups of organisms. A phylogenetic approach to detecting hybridization entails sequencing multiple loci across the genomes of a group of species of interest, reconstructing their gene trees, and exploit- ing their differences as signal of hybridization. However, methods that follow this approach mostly ignore population effects, such as incomplete lineage sorting (ILS). Given that hybridization occurs between closely related organisms, ILS may very well be at play and, hence, must be accounted for in the analysis framework. Methods that account for both hybridization and ILS currently exist for only very limited cases. The contributions of my work are two-fold: • I devised the first parsimony criterion for the inference of phylogenetic networks (topologies alone) in the presence of ILS, along with new algorithms for the inference. • I devised the first likelihood criterion for the inference of phylogenetic networks (topologies, branch lengths, and inheritance probabilities) in the presence of ILS, along with new algorithms for the inference. I have implemented all the algorithms in our open-source, publicly available PhyloNet software package, and studied their performance in extensive simulation studies. Both the parsimony and likelihood approaches show very good performance in terms of identifying the location of hybridization events, as well as estimating the proportions of genes that underwent hybridization. Also, the parsimony approach shows good performance in terms of efficiency on handling large data sets in the experiments. Further, I analyzed two biological data sets (a data sets of yeast genomes and another of house mouse genomes) and found support for hybridization in both. My work will allow, for the first time, systematic phylogenomic analyses of data sets where hybridization is suspected. Thus, biologists will be able now to revisit existing analyses and conduct new ones with richer evolutionary models and inference methods. Further, the computational techniques presented here can be extended to other reticulate evolutionary events, such as horizontal gene transfer, which are believed to be ubiquitous in bacteria.
Multilocus test for nuclear introgression between Macaca mulatta and M fascicularis: Evidence for gene flow in macaques
(2008) Stevison, Laurie Sherie; Kohn, Michael H.; Wiess, Olga K.; Weiss, Harry C.; Queller, David C.; Whitney, Ken; Kronforst, Marcus
Introgression due to hybridization is important for our understanding of species divergence. In this study, we analyze potential introgression between Macaca mulatta and M fascicularis using DNA sequences from 19 genes. While the putative introgression between these species has been studied previously, it has not been analyzed using nuclear loci from multiple chromosomes. Phylogenetic analyses of these genes revealed shared variation at several of the loci. Neutrality tests indicated balancing selection did not fully account for these shared polymorphisms. Testing the null model of Isolation with Migration (IM) indicated interspecific gene flow caused the shared variation, revealing significant gene flow from M mulatta into M fascicularis (2Nm=l.23) and very limited gene flow from M fascicularis into M mulatta (2Nm=0.07). This asyrtlmetry is consistent with previously reported differences in male aggression between these species. Genome-enabled detection of hybridization in these primates opens new avenues of research in genome evolution and speciation.
Network-guided genome-wide studies reveal a complex genetic architecture of warfarin resistance in the Norway rat (Rattus norvegicus)
(2013-09-16) Li, Shuwei; Kohn, Michael H.; Putnam, Nicholas H.; Nakhleh, Luay K.; Kimmel, Marek; Peng, Bo
A fundamental challenge in evolutionary biology and medical genetic research is to connect the phenotype (a disease in humans or an adaptive trait in animals or plants) with the genotype. Using a classical example of an adaptive trait with a strong Mendelian genetic basis - warfarin resistance in the Norway rat (Rattus norvegicus), my dissertation tests the main hypothesis that speculated ‘simple’ adaptive trait has a more complex genetic architecture. Warfarin is an anticoagulant rodenticide used since the 1950s, and also is a widely prescribed blood-thinning drug in human. As a rodenticide, warfarin has initially been very effective. However, resistant rodents have evolved quickly and Vkorc1 (vitamin K epoxide reductase complex subunit 1) is the known resistance gene. As a popular drug, warfarin has a narrow therapeutic window with several genes VKORC1, CYP2C9, CYP4F2 established as biomarkers predicting warfarin dose in humans, suggesting a complex genetic architecture of warfarin resistance in rodents. In my thesis I performed network-guided genomic association studies (NetGWAS) and gene expression analysis to identify candidate genes involved in warfarin resistance based on a sample of ~600 wild rats from 19 populations in Germany. My thesis work revealed that the resistance mutation in Vkorc1 likely is under balancing selection and was recently introduced to the rat population in our study area. A key innovation of my thesis is adopting a NetGWAS approach to prioritize true associations and conducting co-expression network analysis to detect expression changes related to warfarin. My work shows that additional candidate genes are connected to the vitamin K pathway of which Vkorc1 is an essential component. While the validation of identified genes remains a challenge, the value of my thesis for future investigation is shown: one candidate gene Calu (Calumenin) is associated with warfarin resistance in multiple populations and is an essential part of the vitamin K cycle. Finally, my thesis briefly examines the genetics underlying a newly postulated cost of resistance, arterial calcification. This dissertation provides us an innovative framework in which we learned the genetic architecture of an adaptive trait in multiple dimensions: nucleotide or expression variation, genomic distribution and gene-gene interactions.
Population Regulomics: Applying population genetics to the cis-regulome
(2014-02-24) Ruths, Troy; Nakhleh, Luay K.; Jermaine, Christopher M.; Kavraki, Lydia E.; Kohn, Michael H.
Population genetics provides a mathematical and computational framework for understanding and modeling evolutionary processes, and so it is vital for the investigation of biological systems. In its current state, molecular population genetics is exclusively focused on molecular sequences (DNA, RNA, or amino acid sequences), where all application-ready simulators and analytic measures work only on sequence data. Consequently, in the early 2000s, when technologies became available to sequence entire genomes, population genetic approaches were naturally applied to mine out signatures of selection and conservation, resulting in the subfi eld of population genomics. Nearly every present genome project applies population genomic techniques to identify functional information and genome structure. Recent technologies have ushered in a similar wave of genetic information, this time focusing on biological mechanisms operating above the genome, most notably on gene regulation (regulatory networks). In this work, I develop a molecular population genetics approach for gene regulation, called population regulomics, which includes simulators and analytic measurements that operate on populations of regulatory networks. I conducted extensive data analyses to connect the genome with the cis-regulome, developed computationally effi cient simulators, and adapted population genetic measurements on sequence to the regulatory network. By connecting genomic information to cis-regulation, we may apply the wealth of knowledge at the genome level to observed patterns at the regulatory level with unknown evolutionary origin. I demonstrate that by applying population regulomics to the E. coli cis-regulatory network, for the rst time we are able to quantify the evolutionary origins of topological patterns and reveal the surprising amount of neutral signal in the bacterial cis-regulome. Since regulatory networks play a central role in cellular functioning and, consequently, organismal fitness, this new sub-fi eld of population regulomics promises to shed the light of evolution on regulatory mechanisms and, more broadly, on the genetic mechanisms underlying the various phenotypes.
The colonization and divergence patterns of Brandt’s vole (Lasiopodomys brandtii) populations reveal evidence of genetic surfing
(BioMed Central, 2017) Li, Ke; Kohn, Michael H.; Zhang, Songmei; Wan, Xinrong; Shi, Dazhao; Wang, Deng
Background: The colonial habit of Brandt’s vole (Lasiopodomys brandtii) differs from that of most other species of the genus Microtus. The demographic history of this species and the patterns shaping its current genetic structure remain unknown. Here, we explored patterns of genetic differentiation and infered the demographic history of Brandt’s vole populations through analyses of nuclear microsatellite and D-loop sequences. Results: Phylogenetic analyses divided the sampled populations into three main clusters, which represent the southeastern, northeastern and western parts of the total range in Mongolia and China. Molecular data revealed an ancestral area located in the southeast of the extant range, in the Xilinguole District, Inner Mongolia, China, from where Brandt’s vole populations began expanding. A gene flow analysis suggested that the most likely colonization route was from the ancestral area and was followed by subsequent northeastward and westward range expansions. We identified decreases in genetic diversity with increasing distance from the founder population within the newly occupied regions (northeastern and western regions), clinal patterns in the allele frequencies, alleles that were rare in the original area that have become common in the newly occupied regions, and higher genetic differentiation in the expanded range compared with the original one. Conclusion: Our results indicate that L. brandtii most likely originated from the southeastern part of its current geographic range, and subsequently colonized into the northeastern and western parts by expansion. The genetic patterns among the derived populations and with respect to the original population are consistent with that expected under genetic surfing models, which indicated that genetic drift, rather than gene flow, is the predominant factor underlying the genetic structure of expanding Brandt’s vole populations.
The role of environmental variation and host gene flow on the vertical transmission and population prevalence of heritable symbionts
(2017-11-17) Sneck, Michelle E.; Miller, Tom; Egan, Scott P.; Kohn, Michael H.; Bartel, Bonnie
Heritable microbial symbionts, vertically transmitted from maternal host to offspring, have made an indelible contribution to the ecology and evolution of life on earth. For instance, the fixation of symbionts in hosts contributed to pivotal biological shifts, such as the evolution of vascular plants and eukaryotic cells. Vertically transmitted symbionts are often specialized to host genotypes and confer fitness benefits to hosts, including protection against abiotic and biotic stress. Despite their ubiquity and strong influence on hosts, our understanding of what drives the prevalence and persistence of heritable symbionts lags behind that of macro-organisms. Two factors are theorized to determine equilibrium frequencies of heritable symbionts: 1) symbiont vertical transmission rates, and 2) the relative fitness of symbiotic and non-symbiotic hosts. Therefore, characterizing when and how these factors vary in host populations are necessary first steps to predicting the population dynamics of heritable symbionts. Here, I used large-scale field surveys, greenhouse and common garden experiments, as well as demographic modeling approaches to test the hypothesis that outcrossing (i.e., gene flow) between genetically distant hosts disrupts symbiosis. Specifically, host outcrossing is hypothesized to create genetic incompatibilities between sexually reproducing hosts and their specialized clonal symbionts, which may reduce both vertical transmission rates and symbiont mediated mutualistic benefits. First, I found that symbiont prevalence in one host species negatively associated with drought, while symbiont genotype explained residual variation in vertical transmission rates. These results suggest that symbiont genotype, and to a lesser extent, climate variables play roles in shaping symbiont population dynamics, but substantial variability was unexplained. Second, I manipulated gene flow between hosts along a gradient of genetic distances and determined that symbiont vertical transmission was robust to host outcrossing, which remained high for several host generations. Lastly, I quantified the net effect of host outcrossing on symbiont population dynamics. Contrary to our hypothesis, host outcrossing did not disrupt mutualistic benefits of symbiosis, and instead, buffered hosts against deleterious effects of outbreeding depression. Together, my work provides strong evidence that host outcrossing does not disrupt symbiosis, and alternatively demonstrates that heritable symbionts are important players in the population dynamics of outcrossing hosts.
Towards Accurate Reconstruction of Phylogenetic Networks
(2012-09-05) Park, HyunJung; Nakhleh, Luay K.; Kohn, Michael H.; Jermaine, Christopher M.
Since Darwin proposed that all species on the earth have evolved from a common ancestor, evolution has played an important role in understanding biology. While the evolutionary relationships/histories of genes are represented using trees, the genomic evolutionary history may not be adequately captured by a tree, as some evolutionary events, such as horizontal gene transfer (HGT), do not fit within the branches of a tree. In this case, phylogenetic networks are more appropriate for modeling evolutionary histories. In this dissertation, we present computational algorithms to reconstruct phylogenetic networks from different types of data. Under the assumption that species have single copies of genes, and HGT and speciation are the only events through the course of evolution, gene sequences can be sampled one copy per species for HGT detection. Given the alignments of the sequences, we propose systematic methods that estimate the significance of detected HGT events under maximum parsimony (MP) and maximum likelihood (ML). The estimated significance aims at addressing the issue of overestimation of both optimization criteria in the search for phylogenetic networks and helps the search identify networks with the ``right" number of HGT edges. We study their performance on both synthetic and biological data sets. While the studies show very promising results in identifying HGT edges, they also highlight the issues that are challenging for each criterion. We also develop algorithms that estimate the amount of HGT events and reconstruct phylogenetic networks by utilizing the pairwise Subtree-Prune-Regraft (SPR) operation from a collection of trees. The methods produce good results in general in terms of quickly estimating the minimum number of HGT events required to reconcile a set of trees. Further, we identify conditions under which the methods do not work well in order to help in the development of new methods in this area. Finally, we extend the assumption for the genetic evolutionary process and allow for duplication and loss. Under this assumption, we analyze gene family trees of proteobacterial strains using a parsimony-based approach to detect evolutionary events. Also we discuss the current issues of parsimony-based approaches in the biological data analysis and propose a way to retrieve significant estimates. The evolutionary history of species is complex with various evolutionary events. As HGT contributes largely to this complexity, accurately identifying HGT will help untangle evolutionary histories and solve important questions. As our algorithms identify significant HGT events in the data and reconstruct accurate phylogenetic networks from them, they can be used to address questions arising in large-scale biological data analyses.

Browsing by Author "Kohn, Michael H."

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