Genetics and Genomics Commons^™

Nitric Oxide Is Involved In Heavy Ion-Induced Non-Targeted Effects In Human Fibroblasts, Megumi Hada, Premkumar B. Saganti, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the …

Transcriptome Analyses Of Tumor-Adjacent Somatic Tissues Reveal Genes Co-Expressed With Transposable Elements, Micky Chung, G. M. Jonaid, Sophia Quinton, Austin Ross, Corinne E. Sexton, Adrian Alberto, Cody Clymer, Daphnie Churchill, Omar Navarro Leija, Mira V. Han

Life Sciences Faculty Research

Background: Despite the long-held assumption that transposons are normally only expressed in the germ-line, recent evidence shows that transcripts of transposable element (TE) sequences are frequently found in the somatic cells. However, the extent of variation in TE transcript levels across different tissues and different individuals are unknown, and the co-expression between TEs and host gene mRNAs have not been examined. Results: Here we report the variation in TE derived transcript levels across tissues and between individuals observed in the non-tumorous tissues collected for The Cancer Genome Atlas. We found core TE co-expression modules consisting mainly of transposons, showing correlated …

A Frameshift Variant In The Chst9 Gene Identified By Family-Based Whole Genome Sequencing Is Associated With Schizophrenia In Chinese Population, Jingchun Chen, Jain-Shing Wu, Travis Mize, Marvi Moreno, Mahtab Hamid, Francisco Servin, Bita Bashy, Zhongming Zhao, Peilin Jia, Ming T. Tsuang, Kenneth S. Kendler, Momiao Xiong, Xiangning Chen

School of Medicine Faculty Research

Recent studies imply that rare variants contribute to the risk of schizophrenia, however, the exact variants or genes responsible for this condition are largely unknown. In this study, we conducted whole genome sequencing (WGS) of 20 Chinese families. Each family consisted of at least two affected siblings diagnosed with schizophrenia and at least one unaffected sibling. We examined functional variants that were found in affected sibling(s) but not in unaffected sibling(s) within a family. Matching this criterion, a frameshift heterozygous deletion of CA (–/CA) at chromosome 18:24722722, also referred to as rs752084147, in the Carbohydrate Sulfotransferase 9 (CHST9) gene, was …

Decline In Telomere Length By Age And Effect Modification By Gender, Allostatic Load And Comorbidities In National Health And Nutrition Examination Survey (1999-2002), Saruna Ghimire, Carl V. Hill, Francisco S. Sy, Rachelle Rodriguez

School of Public Health Faculty Research

Background: This study aims to assess the decline in telomere length (TL) with age and evaluate effect modification by gender, chronic stress, and comorbidity in a representative sample of the US population. Methods: Cross-sectional data on 7826 adults with a TL measurement, were included from the National Health and Nutrition Examination Survey, years 1999–2002. The population rate of decline in TL across 10-year age categories was estimated using crude and adjusted regression. Results: In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20–29 (β = -0.0172, 95% …

Multi-Polygenic Risk Score Prediction Model For Bipolar Disorder, Travis Mize

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bipolar disorder (BP), a severe mental disorder characterized by recurring manic and depressive episodes, has been shown to have a strong genetic underpinning. Current theory suggests that it is the summation of risk alleles, spread across the entirety of the genome, which contributes to the development of BP, as well as other polygenic traits. The comorbid nature of these polygenic traits are often problematic for diagnosticians as the symptomology of the disorders may vary substantially between individuals and can create diagnostic confusion. To alleviate issues such as these, a more objective measure, to be used alongside current diagnostic procedures, is …

Prioritization Of Variants For Investigation Of Genotype-Directed Nutrition In Human Superpopulations, Pascal D. Nilsson, Jacklyn M. Newsome, Henry M. Santos, Martin R. Schiller

Life Sciences Faculty Research

Dietary guidelines recommended by key health agencies are generally designed for a global population. However, ethnicity affects human disease and environment-gene interactions, including nutrient intake. Historically, isolated human populations with different genetic backgrounds have adapted to distinct environments with varying food sources. Ethnicity is relevant to the interaction of food intake with genes and disease susceptibility; yet major health agencies generally do not recommend food and nutrients codified by population genotypes and their frequencies. In this paper, we have consolidated published nutrigenetic variants and examine their frequencies in human superpopulations to prioritize these variants for future investigation of population-specific genotype-directed …

Paired-End Mappability Of Transposable Elements In The Human Genome, Corinne E. Sexton, Mira V. Han

Life Sciences Faculty Research

Though transposable elements make up around half of the human genome, the repetitive nature of their sequences makes it difficult to accurately align conventional sequencing reads. However, in light of new advances in sequencing technology, such as increased read length and paired-end libraries, these repetitive regions are now becoming easier to align to. This study investigates the mappability of transposable elements with 50 bp, 76 bp and 100 bp paired-end read libraries. With respect to those read lengths and allowing for 3 mismatches during alignment, over 68, 85, and 88% of all transposable elements in the RepeatMasker database are uniquely …

A Method For Improving The Accuracy And Efficiency Of Bacteriophage Genome Annotation, Alicia Salisbury, Philippos K. Tsourkas

Life Sciences Faculty Research

Bacteriophages are the most numerous entities on Earth. The number of sequenced phage genomes is approximately 8000 and increasing rapidly. Sequencing of a genome is followed by annotation, where genes, start codons, and functions are putatively identified. The mainstays of phage genome annotation are auto-annotation programs such as Glimmer and GeneMark. Due to the relatively small size of phage genomes, many groups choose to manually curate auto-annotation results to increase accuracy. An additional benefit of manual curation of auto-annotated phage genomes is that the process is amenable to be performed by students, and has been shown to improve student recruitment …

A Method For Improving The Accuracy And Efficiency Of Bacteriophage Genome Annotation, Philippos Tsourkas, Alicia Salisbury

Life Sciences Faculty Research

Bacteriophages are the most numerous entities on Earth. The number of sequenced phage genomes is approximately 8000 and increasing rapidly. Sequencing of a genome is followed by annotation, where genes, start codons, and functions are putatively identified. The mainstays of phage genome annotation are auto-annotation programs such as Glimmer and GeneMark. Due to the relatively small size of phage genomes, many groups choose to manually curate auto-annotation results to increase accuracy. An additional benefit of manual curation of auto-annotated phage genomes is that the process is amenable to be performed by students, and has been shown to improve student recruitment …

Position-Specific Metabolic Probing And Metagenomics Of Microbial Communities Reveal Conserved Central Carbon Metabolic Network Activities At High Temperatures, Scott C. Thomas, Kevin O. Tamadonfar, Cale O. Seymour, Dengxun Lai, Jeremy A. Dodsworth, Senthil K. Murugapiran, Emiley A. Eloe-Fadrosh, Paul Dijkstra, Brian P. Hedlund

Life Sciences Faculty Research

Temperature is a primary driver of microbial community composition and taxonomic diversity; however, it is unclear to what extent temperature affects characteristics of central carbon metabolic pathways (CCMPs) at the community level. In this study, 16S rRNA gene amplicon and metagenome sequencing were combined with 13C-labeled metabolite probing of the CCMPs to assess community carbon metabolism along a temperature gradient (60–95°C) in Great Boiling Spring, NV. 16S rRNA gene amplicon diversity was inversely proportional to temperature, and Archaea were dominant at higher temperatures. KO richness and diversity were also inversely proportional to temperature, yet CCMP genes were similarly represented across …

Novel Algorithms For Ldd Motif Search, Peng Xiao, Martin Schiller, Sanguthevar Rajasekaran

Life Sciences Faculty Research

Background: Motifs are crucial patterns that have numerous applications including the identification of transcription factors and their binding sites, composite regulatory patterns, similarity between families of proteins, etc. Several motif models have been proposed in the literature. The (l,d)-motif model is one of these that has been studied widely. However, this model will sometimes report too many spurious motifs than expected. We interpret a motif as a biologically significant entity that is evolutionarily preserved within some distance. It may be highly improbable that the motif undergoes the same number of changes in each of the species. To address this issue, …

The Anti-Sigma Factor Muca Of Pseudomonas Aeruginosa: Dramatic Differences Of A Muca22 Vs. A Δmuca Mutant In Anaerobic Acidified Nitrite Sensitivity Of Planktonic And Biofilm Bacteria In Vitro And During Chronic Murine Lung Infection, Warunya Panmanee, Shengchang Su, Michael J. Schurr, Gee W. Lau, Xiaoting Zhu, Zhaowei Ren, Cameron T. Mcdaniel, Long J. Lu, Dennis E. Ohman, Daniel A. Muruve, Ralph J. Panos, Hongwei D. Yu, Thomas B. Thompson, Boo Shan Tseng, Daniel J. Hassett

Life Sciences Faculty Research

Mucoid mucA22 Pseudomonas aeruginosa (PA) is an opportunistic lung pathogen of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients that is highly sensitive to acidified nitrite (A-NO2-). In this study, we first screened PA mutant strains for sensitivity or resistance to 20 mM A-NO2- under anaerobic conditions that represent the chronic stages of the aforementioned diseases. Mutants found to be sensitive to A-NO2- included PA0964 (pmpR, PQS biosynthesis), PA4455 (probable ABC transporter permease), katA (major catalase, KatA) and rhlR (quorum sensing regulator). In contrast, mutants lacking PA0450 (a putative phosphate transporter) and PA1505 (moaA2) were A-NO2- resistant. However, …

Investigating The Dna-Binding Site For Virb, A Key Transcriptional Regulator Of Shigella Virulence Genes, Using An In Vivo Binding Tool, Monika M.A. Karney, Joy A. Mckenna, Natasha Weatherspoon-Griffin, Alexander D. Karabachev, Makensie E. Millar, Eliese A. Potoceck, Helen J. Wing

Life Sciences Faculty Research

The transcriptional anti-silencing and DNA-binding protein, VirB, is essential for the virulence of Shigella species and, yet, sequences required for VirB-DNA binding are poorly understood. While a 7-8 bp VirB-binding site has been proposed, it was derived from studies at a single VirB-dependent promoter, icsB. Our previous in vivo studies at a different VirB-dependent promoter, icsP, found that the proposed VirB-binding site was insufficient for regulation. Instead, the required site was found to be organized as a near-perfect inverted repeat separated by a single nucleotide spacer. Thus, the proposed 7-8 bp VirB-binding site needed to be re-evaluated. Here, we engineer …

Complete Genome Sequences Of 18 Paenibacillus Larvae Phages From The Western United States, Bryan D. Merrill, Christopher P. Fajardo, Jared A. Hilton, Ashley M. Payne, Andy T. Ward, Jamison K. Walker, Aziza Dhalai, Cameron Imahara, James Mangohig, Josh Monk, Cristian Pascacio, Padmani Rai, Alicia Salisbury, Kathie Velez, Travis J. Bloomfield, Brett Buhler, Steven G. Duncan, David A. Fuhriman, Josil George, Kiel Graves, Karli Graves, Hunter L. Hill, Michelle Kim, Bradley K. Knabe, Devin B. Ririe, Spencer L. Rogers, Casey Stamereilers, Michael B. Stephenson, Brittian K. Usher, Colton S. Ward, Jacob M. Withers

Life Sciences Faculty Research

We present here the complete genomes of 18 phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. The phages were isolated between 2014 and 2016 as part of an undergraduate phage discovery course at Brigham Young University. The phages were isolated primarily from bee debris and lysogens.

Identification Of Chst9 As A Candidate Gene For Schizophrenia From Whole Genome Sequencing, Christopher Sharp, Jingchun Chen, Marvi Moreno, Mahtab Hamid, Francisco Servin, Bita Bashy, Travis Mize

LSAMP Poster Presentations

Recent results imply that rare variants contribute to the risk of schizophrenia. We conducted whole genome sequencing for 99 subjects from 20 Chinese families (parents and at least two siblings with a schizophrenia diagnosis and one unaffected sibling). Of the 9 frameshift mutations identified in more than 2 families, one was at chromosome 10:125780762 on the Carbohydrate Sulfotransferase 15 (CHST15) gene and another at chromosome 18:24722723 on the Carbohydrate Sulfotransferase 9 (CHST9) gene. We observed these deletions in 4 affected persons of two families from whole. At least two types of mutations (one or three bases insertion) have been identified …

Complete Genome Sequences Of Paenibacillus Larvae Phages Halcyone, Heath, Scottie, And Unity From Las Vegas, Nevada, Diane G. Yost, Carolyn Chang, Lucy Leblanc, Erin Cassin, Ceara Peterman, Padmani Rai, Alicia Salisbury, Nicolas Barroga, Ramiro Cisneros, Joseph Fersini, Jonathan Juste, Juvie Ines, Gabriel Leyva, Dyanne Macalinao, Spencer Muscelli, Gustavo S. Reyes, Heather Rhoden, Rodney Tan, Erika Torres, Krystal Tran, Georgette Uriarte-Valle, Christopher Wallace, Simon Wong, Kevin Ayala-Pineda, Vanessa Cadiz, Tiffany Jeanite, Sophia Nhan, Julianne H. Grose, Christy Strong, Penny S. Amy, Philippos K. Tsourkas

Life Sciences Faculty Research

We present the complete genome sequences of four phages that infect Paenibacillus larvae, the causative agent of American foulbrood disease in honeybees. The phages were isolated from beehives and beeswax products from Las Vegas, Nevada. The genomes are 50 to 55 kbp long and use the “direct terminal repeats” DNA-packaging strategy.

Effect Of Larval Starvation On Lipid Content Of Drosophila Melanogaster Over 15 Days, Fabian Leija, Allen Gibbs

LSAMP Poster Presentations

Starvation-resistant Drosophila melanogaster, common fruit flies, deriving from 121 generations of starvation selection, have resulted in genetically, behaviorally, and physiologically different individuals compared to non-resistant counterparts. Starvation-resistant Drosophila are more obese, containing twice as much lipids as control flies.This is a result of starvation-resistant fly larva feeding for 5 days and then entering the pupa stage while non-resistant flies only feed for 4 days.

In this experiment, we hope to answer the question of whether the starvation-resistant flies are genetically predisposed to be substantially more obese than wild populations or if it is a result of this alternate behavior …

Genomic Analysis Of 48 Paenibacillus Larvae Bacteriophages, Casey Stamereilers, Christopher P. Fajardo, Jamison K. Walker, Katterinne N. Mendez, Eduardo Castro-Nallar, Julianne H. Grose, Sandra Hope, Philippos K. Tsourkas

Life Sciences Faculty Research

The antibiotic-resistant bacterium Paenibacillus larvae is the causative agent of American foulbrood (AFB), currently the most destructive bacterial disease in honeybees. Phages that infect P. larvae were isolated as early as the 1950s, but it is only in recent years that P. larvae phage genomes have been sequenced and annotated. In this study we analyze the genomes of all 48 currently sequenced P. larvae phage genomes and classify them into four clusters and a singleton. The majority of P. larvaephage genomes are in the 38–45 kbp range and use the cohesive ends (cos) DNA-packaging strategy, while a minority have genomes …

Complete Genome Sequences Of Paenibacillus Larvae Phages Bn12, Dragolir, Kiel007, Leyra, Likha, Pagassa, Pbl1c, And Tadhana, Jamison K. Walker, Bryan D. Merrill, Jordan A. Berg, Aziza Dhalai, Douglas W. Dingman, Chris P. Fajardo, Kiel Graves, Hunter L. Hill, Jared A. Hilton, Cameron Imahara, Bradley K. Knabe, James Mangohig, Josh Monk, Heejin Mun, Ashley M. Payne, Alicia Salisbury, Casey Stamereilers, Kathie Velez, Andy T. Ward, Donald P. Breakwell, Julianne H. Grose, Sandra Hope, Philippos K. Tsourkas

Life Sciences Faculty Research

We present here the complete genomes of eight phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA.

Gene Expression Profiling In The Larval Fat Body Of Desiccation Selected Drosophila Melanogaster, Adriana Michelle Charles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster selected for resistance to desiccation (no food or water) display slower development and a higher body mass compared to fed controls due to an extended third larval instar. I hypothesize that desiccation selected D. melanogaster larvae will have a different gene expression profile compared to fed controls. Separate populations of D. melanogaster were subjected to desiccation (no food or water), starvation (no food) until 80-85% mortality, for 75 generations. mRNA from the larval fat body was collected at 88 hours, 96 hours, 112 hours and 120 hours post-hatching. Four replicate samples were used for each condition and time …

The Role Of Mfd In Stationary-Phase Oxidative Damage Repair In Bacillus Subtilis, Katelyn E. Porter

UNLV Theses, Dissertations, Professional Papers, and Capstones

Since the 1950’s it has been shown that bacterial cells accumulate mutations even in non- dividing conditions, but how this type of mutation occurs is still highly debated. In Bacillus subtilis, Mfd, a precursor of the nucleotide excision repair (NER) system, mediates the formation of mutations in stationary-phase or non-replicating cells. In growing cells, Mfd recruits repair when RNA polymerase is stalled during transcription; it then recruits proteins from NER to repair damage. Here, we examine the hypothesis that Mfd mediates the formation of mutations by interacting with cellular components that repair reactive oxygen species (ROS), a natural byproduct of …

Stationary-Phase Mutagenesis In Stressed Bacillus Subtilis Cells Operates By Mfd-Dependent Mutagenic Pathways, Martha Gómez-Marroquín, Holly A. Martin, Amber Pepper, Mary E. Girard, Amanda Kidman, Carmen Vallin, Ronald E. Yasbin, Mario Pedraza-Reyes, Eduardo Robleto

Life Sciences Faculty Research

In replication-limited cells of Bacillus subtilis, Mfd is mutagenic at highly transcribed regions, even in the absence of bulky DNA lesions. However, the mechanism leading to increased mutagenesis through Mfd remains currently unknown. Here, we report that Mfd may promote mutagenesis in nutritionally stressed B. subtilis cells by coordinating error-prone repair events mediated by UvrA, MutY and PolI. Using a point-mutated gene conferring leucine auxotrophy as a genetic marker, it was found that the absence of UvrA reduced the Leu+ revertants and that a second mutation in mfd reduced mutagenesis further. Moreover, the mfd and polA mutants presented low but …

Sex Determination Using Discriminant Function Analysis In Hispanic Children And Adolescents: A Lateral Cephalometric Study, Alyssa E. Sprowl

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lateral cephalometric radiographs have been used for years to help diagnose skeletal and dental patterns in Orthodontics. Within the last decade, these radiographs have caught the interest of the department of Anthropology for the identification of gender within the adult and adolescent population. Numerous publications have been made but failed to identify sexual dimorphism in the pre-adolescent population. 303 lateral cephalograms of pre and post Latino adolescence age ranging from 6.5 to 17.9 years old were obtained from University of Nevada, Las Vegas (UNLV) digital database. 25 variables were identified and plotted with all linear and angular measurements transferred into …

Time-Dependent Random Effect Poisson Random Field Model For Polymorphism Within And Between Two Related Species, Shilei Zhou

UNLV Theses, Dissertations, Professional Papers, and Capstones

Molecular evolution is partially driven by mutation, selection, random genetic drift, or combination of the three factors. To quantify the magnitude of these genetic forces, a previously developed time-dependent fixed effect Poisson random field model provides powerful likelihood and Bayesian estimates of mutation rate, selection coefficient, and species divergence time. The assumption of the fixed effect model that selection intensity is constant within a genetic locus but varies across genes is obviously biologically unrealistic, but it serves the original purpose of making statistical inference about selection and divergence between two related species they are individually at mutation-selection-drift inequilibrium. By relaxing …

Relationship Of Global Dna Methylation With Cardiovascular Fitness And Body Composition, Michael Steele Jarrett

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Global DNA Methylation (GDM), an epigenomic modification has been linked to the development of Cardiovascular Disease and its risk factors. Purpose: The purpose of this study was to determine if there is a significant correlation between GDM and cardiovascular fitness, as well as, measures of body composition. Methodology: 26 apparently healthy, adults (11 males) completed a physical activity and diet questionnaire, as well as, had a small blood sample (600μL) collected via finger prick for the determination of GDM. Body composition was assessed by means of a Dual-Energy X-ray Absorptiometry (DEXA) scan, while cardiovascular fitness was evaluated by the …

The Putative Role Of Resveratrol In Sirt-1 Mediated Modulation Of The Vitamin D Pathway, Angelika Dampf Stone, Shane F. Batie, G. Kerr Whitfield, Mark R. Haussler, Peter W. Jurutka

American Association for the Advancement of Science Pacific Conference

The nuclear vitamin D receptor (VDR) modulates gene transcription in 1,25-dihydroxyvitamin D (1,25D) target tissues such as kidney, colon, and bone. The 1,25D hormone is derived from vitamin D in the skin or from the diet, and binds to and activates the VDR. We have previously shown that resveratrol, an antioxidant found in the skin of red grapes, has the ability to activate the VDR signaling pathway. Moreover, cells treated with both resveratrol and 1,25D resulted in an additive or even synergistic stimulation of VDR-mediated transcription compared to cells treated with 1,25D alone. Based on these initial results, experiments were …

A Comprehensive Research Framework For Geographic Parthenogenesis In Whiptail Lizards (Genus Aspidoscelis), Adam Leland

UNLV Theses, Dissertations, Professional Papers, and Capstones

One of the most compelling topics in biology has been the ubiquity of sexual reproduction in living organisms. Because the ecological and evolutionary advantages of sex are well founded, those organisms that reproduce asexually remain enigmatic. Parthenogenesis, the clonal reproduction of an all-female species without the need for males, is a relatively common form of asexual reproduction in vertebrates, and has been subject of numerous academic investigations. Many parthenogenic organisms also share aspects of their geographic distributions, such as inhabiting higher latitudes, higher altitudes, islands or island-like habitats, xeric environments, and marginal, disturbed or ecotonal habitats relative to their sexual …

Biogeography And Phylogeny Of Aigarchaeota, A Novel Phylum Of Archaea, Gisele Braga Goertz, Brian P. Hedlund

McNair Poster Presentations

‘Aigarchaeota’ is a candidate phylum of Archaea known only by 16S rRNA gene fragments from cultiva­tion-independent microbial surveys and a single composite genome from Candidatus ‘Caldiarchaeum sub­terraneum’, an inhabitant of a subterranean gold mine in Japan. Gene sequences associated with ‘Aigarchaeo­ta’ have been found in a variety of geothermal habits, however a comprehensive analysis of the phylogeny and distribution of ‘Aigarchaeota’ has not yet been done. Public databases were mined for 16S rRNA gene sequences related to known ‘Aigarchaeota’ and a combination of approaches were used to rigorously define the phylogenetic boundaries of the phylum, investigate its distribution, and …

A Genetic, Transgenic, And Transcriptomic Analysis Of Larval Salivary Gland Physiology In Drosophila Melanogaster, Elana A. Paladino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cholesterol is the precursor to a unique class of lipophilic signaling molecules called steroid hormones that initiate the development of sexual characteristics, reactions to stress, and maintenance of metabolism, among many other functions. Although much progress has been made in understanding the function of these signaling hormones, we do not fully understand how a single steroid can cause many distinct, tissue-specific responses. Drosophila melanogaster is an effective model for understanding steroid hormone action because of its simplicity. The steroid molting hormone 20-hydroxyecdysone (hereafter, 20E) is the primary active steroid in Drosophila and mediates not only larval molts and the emergence …

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Research

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative …