A5088243805- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Genetic Neurodegenerative Diseases
- Genetic diversity and population structure
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Evolution and Genetic Dynamics
- Space exploration and regulation
- Construction Engineering and Safety
- Paleontology and Evolutionary Biology
- Amphibian and Reptile Biology
- Molecular Biology Techniques and Applications
- Mycobacterium research and diagnosis
- Connective tissue disorders research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Duke University Hospital
2022-2025
Duke Medical Center
2022-2025
Duke University
2021-2025
Medical University of Białystok
2024
Stanford University
2010-2019
Howard Hughes Medical Institute
2010-2018
University of California, Santa Cruz
2005-2012
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis 29 eutherian genomes. We confirm that at least 5.5% human undergone purifying selection, locate constrained elements covering ∼4.2% genome. use evolutionary signatures comparisons with experimental data sets to suggest candidate functions ∼60% bases. These reveal small number new coding exons, stop codon readthrough events over 10,000 regions...
The evolution of the amniotic egg was one great evolutionary innovations in history life, freeing vertebrates from an obligatory connection to water and thus permitting conquest terrestrial environments. Among amniotes, genome sequences are available for mammals birds, but not non-avian reptiles. Here we report sequence North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes highly syntenic with chicken microchromosomes, yet do exhibit high GC...
The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition retroelements may play a role, but its global importance, beyond few well described examples for isolated genes, is not clear. We report LTR class I endogenous retrovirus (ERV) impact considerably the transcriptional network human tumor suppressor protein p53. A total 1,509 ≈319,000 ERV regions have near-perfect p53 DNA binding site. LTR10 MER61 families...
Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications existing functional elements. However, study regions excludes elements that descended from previously neutral regions. Here, we demonstrate fastest-evolved genome, term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged an episodic burst directional positive selection prior to human-Neanderthal split,...
At least 5% of the human genome predating mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% genome. Thus, majority conserved and, by extension, functional sequence in seems be nonexonic. Recent work has highlighted a handful cases where mobile element insertions resulted introduction novel nonexonic elements. Here, we present genome-wide survey 10,402 constrained elements that all been deposited...
Patterns of vertebrate gene regulation have changed during the course evolution.
The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. found that the causal strain carried an ancestral full-length version type VII-secreted effector EsxM rather than truncated present in modern Mtb lineages. variant exacerbated through enhancement macrophage motility, increased egress macrophages from...
Taking advantage of the complete genome sequences several mammals, we developed a novel method to detect losses well-established genes in human through syntenic mapping gene structures between human, mouse, and dog genomes. Unlike most previous genomic methods for pseudogene identification, this analysis is able differentiate from pseudogenes formed shortly after segmental duplication or generated via retrotransposition. Therefore, it enables us find that were inactivated long their birth,...
Recent research supports the view that changes in gene regulation, as opposed to genes themselves, play a significant role morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers are now able use available 29 mammalian genomes measure selective constraint at level of This detailed map suggests co-opt fragments mobile elements act regulatory sequence large scale. In human genome we detect over 280,000 putative elements, totaling...
The evolution of avian feathers has recently been illuminated by fossils and the identification genes involved in feather patterning morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics more than 600,000 conserved regulatory elements, we show that patterns genome vicinity are consistent with a major role for innovation feathers. Rates at elements exhibit an extended period peaks ancestors amniotes archosaurs. We estimate 86% such...
The Threespine Stickleback, Gasterosteus aculeatus, is an emerging model system for understanding the genomic basis of vertebrate adaptation. A strength that marine populations have repeatedly colonized freshwater environments, serving as natural biological replicates. These replicates enabled researchers to efficiently identify phenotypes and genotypes under selection during this transition. While repeated adaptation has occurred throughout northern hemisphere, Cook Inlet in south-central...
We report that 18 conserved, and by extension functional, elements in the human genome are result of retroposon insertions evolving under purifying selection mammals. show evidence 1 regulates expression ASXL3 during development encoding an alternatively spliced exon causes nonsense-mediated decay transcript. The gave rise to these functional was quickly inactivated mammalian ancestor, all traces it have been lost due neutral decay. However, tuatara has maintained a near-ancestral version...
Spinocerebellar ataxia type 7 (SCA7) is a genetic neurodegenerative disorder caused by CAG-polyglutamine repeat expansion. Purkinje cells (PCs) are central to the pathology of ataxias, but their low abundance in cerebellum underrepresents transcriptomes sequencing assays. To address this issue, we developed PC enrichment protocol and sequenced individual nuclei from mice patients with SCA7. Single-nucleus RNA SCA7-266Q revealed dysregulation cell identity genes affecting glia PCs....
Abstract Understanding the mechanisms leading to new traits or additional features in organisms is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly different fish genera alter length and number prominent dorsal spines classify stickleback species. In Gasterosteus aculeatus (typically ‘three-spine sticklebacks’), variant allele genetically linked shortening an existing spine adding spine. Apeltes quadracus ‘four-spine associated with...
ABSTRACT Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. SCA7 patients display striking loss of Purkinje cell (PC) neurons with disease progression; however, PCs are rare, making them difficult to characterize. We developed PC nuclei enrichment protocol and applied it single-nucleus RNA-seq knock-in mouse model. Our results unify prior observations into central mechanism identity loss, impacting both glia PCs,...
We present a method to detect copy number variants (CNVs) that are differentially between two groups of sequenced samples. use finite-state transducer where the emitted read depth is conditioned on mappability and GC-content all reads occur at given base position. In this model, within region mixture binomials, which in simulations matches more closely than often-used negative binomial distribution. The analyzes samples simultaneously, preserving uncertainty as breakpoints magnitude CNVs an...
Abstract Summary Many existing software libraries for genomics require researchers to pick between competing considerations: the performance of compiled languages and accessibility interpreted languages. Go, a modern language, provides an opportunity address this conflict. We introduce Gonomics, open-source collection command line programs bioinformatic implemented in Go that unites readability genomic analyses. Gonomics contains packages read, write, manipulate wide array file formats (e.g....
Taking advantage of the complete genome sequences several mammals, we developed a novel method to detect losses well-established genes in human through syntenic mapping gene structures between human, mouse, and dog genomes.Unlike most previous genomic methods for pseudogene identification, this analysis is able differentiate from pseudogenes formed shortly after segmental duplication or generated via retrotransposition.Therefore, it enables us find that were inactivated long their birth,...
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