A5038631849- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- interferon and immune responses
- Genomics and Phylogenetic Studies
- Evolution and Genetic Dynamics
- HIV Research and Treatment
- Plant Virus Research Studies
- RNA and protein synthesis mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Bacteriophages and microbial interactions
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- Viral Infections and Immunology Research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Genetic diversity and population structure
- Insect symbiosis and bacterial influences
- Immune Response and Inflammation
- Genetics, Aging, and Longevity in Model Organisms
- Bacterial biofilms and quorum sensing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
Howard Hughes Medical Institute
2016-2025
Fred Hutch Cancer Center
2016-2025
Seattle University
2007-2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2013-2023
Cancer Research Center
2012-2022
Office of Basic Energy Sciences
2008-2019
University of Washington
2007-2019
University of Rochester
1997-2001
North Seattle College
2000
Primate genomes encode a variety of innate immune strategies to defend themselves against retroviruses. One these, TRIM5α, can restrict diverse retroviruses in species-specific manner. Thus, whereas rhesus TRIM5α strongly HIV-1, human only has weak HIV-1 restriction. The biology restriction suggests that it is locked an antagonistic conflict with the proteins encoding viral capsid. Such interactions frequently result rapid amino acid replacements at protein–protein interface, as each genetic...
A comprehensive phylogenetic analysis was conducted of non-long-terminal-repeat (non-LTR) retrotransposons based on an extended sequence alignment their reverse transcriptase (RT) domain. The 440 amino acid positions used included a region proposed to be similar the "thumb" right-handed RT structure found in retroviruses. All identified non-LTR elements could grouped into 11 distinct clades. Using rates change derived from studies vertical inheritance R1 and R2 arthropods as comparison, we...
Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up genetic conflict between Vif genes. This kind leads rapid fixation mutations alter amino acids at protein-protein interface,...
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...
Abstract Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such has greatly increased recent years, but the lack naming conventions for them led to a variety styles, multiple synonyms and misleading homographs obscure variant relationships complicate database searches. We propose here unified nomenclature all five classes histones uses consistent flexible produce names informative readily searchable. builds on...
The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark speciation. One the earliest isolating arise incipient species sterility heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid have been identified animals: Odysseus, JYalpha, Overdrive Drosophila Prdm9 (Meisetz) mice. Mouse encodes protein with KRAB motif, histone methyltransferase domain several zinc fingers. difference single finger distinguishes alleles cause from those...
Multiple stringent confinement strategies should be used whenever possible
The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate Vpx, which targets for degradation. However, only two of eight lentivirus lineages encode whereas its paralog, Vpr, conserved across all extant lentiviruses. We find that not multiple Vpx also some Vpr proteins are able to degrade SAMHD1, such antagonism led dramatic positive selection subfamily Cercopithecinae. Residues have evolved under precisely...
Innate immune detection of nucleic acids is important for initiation antiviral responses. Detection intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members AIM2-like receptor (ALR) gene family contribute to each these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine perform a phylogenetic analysis mammalian ALRs, revealing remarkable diversification receptors among mammals. We characterize...
Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. The centromeric histone H3 variant, CenH3, is defining chromatin component of centromeres most eukaryotes, including animals, fungi, plants, protists. In this study, using detailed genomic transcriptome analyses, we show CenH3 was lost independently at least four lineages insects. Each these represents an...
Phylogenetic analyses suggest that long-terminal repeat (LTR) bearing retrotransposable elements can acquire additional open-reading frames enable them to mediate infection. Whereas this process is best documented in the origin of vertebrate retroviruses and their acquisition an envelope ( env ) gene, similar independent events may have occurred insects, nematodes, plants. The origins -like genes are unclear, often masked by antiquity original acquisitions rapid rate evolution. In report, we...
Abstract Centromeric DNA is generally composed of large blocks tandem satellite repeats that change rapidly due to loss old arrays and expansion new repeat classes. This extreme heterogeneity centromeric difficult reconcile with the conservation eukaryotic chromosome segregation machinery. Histone H3-like proteins, including Cid in Drosophila melanogaster, are a unique chromatin component centromeres. In comparisons between closely related species Drosophila, we find an excess replacement...
We have conducted a phylogenetic analysis of the Ribonuclease HI (RNH) domains present in Eubacteria, Eukarya, all long-term repeat (LTR)-bearing retrotransposons, and several late-branching clades non-LTR retrotransposons. Analysis this simple yet highly conserved enzymatic domain from these disparate sources provides surprising insights into evolution eukaryotic First, it indicates that lineage elements leading to vertebrate retroviruses acquired new RNH either retrotransposons or host...
Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins Rebecca S. LaRue, Valgerdur Andresdottir, Yannick Blanchard, Silvestro G. Conticello, David Derse, Michael Emerman, Warner C. Greene, Stefan R. Jonsson, Nathaniel Landau, Martin Lochelt, Harmit Malik, H. Malim, Carsten Munk, Stephen J. O’Brien, Vinay K. Pathak, Klaus Strebel, Simon Wain-Hobson, Xiao-Fang Yu, Naoya Yuhki, Reuben Harris*
ABSTRACT A phylogenetic analysis of the Ty3/Gypsy group retrotransposons identified a conserved domain (GPY/F) present in integrases several members this as well certain vertebrate retroviruses. The suggested an evolutionary scheme for acquisition and loss GPY/F chromodomain module integrase encoded by elements that may direct targeting specificity host genome.