Morgan Wirthlin
A5038619849- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Animal Vocal Communication and Behavior
- Animal Behavior and Reproduction
- Chromosomal and Genetic Variations
- Marine animal studies overview
- Genetic diversity and population structure
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Bat Biology and Ecology Studies
- CRISPR and Genetic Engineering
- Evolution and Paleontology Studies
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Associations and Epidemiology
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital heart defects research
- Plant and animal studies
- Neural dynamics and brain function
- Virus-based gene therapy research
- Neurological diseases and metabolism
- Pluripotent Stem Cells Research
Carnegie Mellon University
2018-2025
Allen Institute
2022-2024
Allen Institute for Brain Science
2022-2024
University of Pittsburgh
2022-2023
Neuroscience Institute
2020-2023
Howard Hughes Medical Institute
2023
University of California, Santa Cruz
2023
University of California, Riverside
2023
University of Massachusetts Chan Medical School
2023
Science for Life Laboratory
2023
To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis 48 species representing all orders Neoaves using phylogenomic methods created to handle data. We recovered highly resolved tree that confirms previously controversial sister or close relationships. identified first divergence in Neoaves, two groups named Passerea and Columbea, independent lineages diverse convergently evolved land water bird species. Among Passerea, infer common ancestor core...
Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential song speech not found most other species. Comparisons of transcriptomes song-learning relative to nonlearners identified convergent gene expression specializations specific regions avian learners humans. The strongest shared profiles relate bird motor striatal nuclei, respectively, with human laryngeal cortex parts the striatum control production learning. Most...
Abstract The importance of the Gallus gallus (chicken) as a model organism and agricultural animal merits continuation sequence assembly improvement efforts. We present new version chicken genome (Gallus_gallus-5.0; GCA_000002315.3), built from combined long single molecule sequencing technology, finished BACs, improved physical maps. In overall assembled bases, we see gain 183 Mb, including 16.4 Mb in placed chromosomes with corresponding percentage intact repeat elements characterized. Of...
Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half...
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning...
Abstract Background Birds are one of the most highly successful and diverse groups vertebrates, having evolved a number distinct characteristics, including feathers wings, sturdy lightweight skeleton unique respiratory urinary/excretion systems. However, genetic basis these traits is poorly understood. Results Using comparative genomics based on extensive searches 60 avian genomes, we have found that birds lack approximately 274 protein coding genes present in genomes vertebrate lineages for...
Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (
The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different...
Highlights•The blue-fronted Amazon, Amazona aestiva, and other parrots share unique novel genes•Convergent selection in long-lived birds suggests new lifespan-influencing genes•Parrot genomes genetic changes related to genes critical for brain function•Similar parrot human suggest convergent evolution of cognitionSummaryParrots are one the most distinct intriguing groups birds, with highly expanded brains [1], developed cognitive [2] vocal communication [3] skills, a long lifespan compared...
The arcopallium, a key avian forebrain region, receives inputs from numerous brain areas and is major source of descending sensory motor projections. While there evidence arcopallial subdivisions, the internal organization or arcopallium not well understood. also considered homologue mammalian deep cortical layers and/or amygdalar but one-to-one correspondences are controversial. Here we present molecular characterization in zebra finch, passerine songbird species model organism for vocal...
An in-depth understanding of the genetics and evolution brain function behavior requires a detailed mapping gene expression in functional circuits across major vertebrate clades. Here we present Zebra finch Expression Brain Atlas (ZEBrA; www.zebrafinchatlas.org, RRID: SCR_012988), web-based resource that maps genes linked to broad range functions onto zebra finches. ZEBrA is first its kind atlas for bird species any sauropsid. ZEBrA's >3,200 high-resolution digital images situ hybridized...
Evolutionary conservation is an invaluable tool for inferring functional significance in the genome, including regions that are crucial across many species and those have undergone convergent evolution. Computational methods to test sequence dominated by algorithms examine ability of one or more nucleotides align large evolutionary distances. While these nucleotide alignment-based approaches proven powerful protein-coding genes some non-coding elements, they fail capture enhancers, distal...
Recent discoveries of extreme cellular diversity in the brain warrant rapid development technologies to access specific cell populations within heterogeneous tissue. Available approaches for engineering-targeted new neuron subtypes are low yield, involving intensive transgenic strain or virus screening. Here, we present Specific Nuclear-Anchored Independent Labeling (SNAIL), an improved virus-based strategy labeling and nuclear isolation from SNAIL works by leveraging machine learning other...
Introduction: Transcriptional regulation is an important process wherein non-protein coding enhancer sequences play a key role in determining cell type identity and phenotypic diversity. In neural tissue, these gene regulatory processes are crucial for coordinating plethora of interconnected regionally specialized types, ensuring their synchronized activity generating behavior. Recognizing the intricate interplay brain imperative, as mounting evidence links neurodevelopment neurological...
Songbirds (oscine Passeriformes) are among the most diverse and successful vertebrate groups, comprising almost half of all known bird species. Identifying genomic innovations that might be associated with this success, as well characteristic songbird traits such vocal learning brain circuits underlie behavior, has proven difficult, in part due to small number avian genomes available until recently. Here we performed a comparative analysis 48 identify features unique songbirds, an initial...
Recent large genome-wide association studies have identified multiple confident risk loci linked to addiction-associated behavioral traits. Most genetic variants traits lie in noncoding regions of the genome, likely disrupting cis-regulatory element (CRE) function. CREs tend be highly cell type-specific and may contribute functional development neural circuits underlying addiction. Yet, a systematic approach for predicting impact on specific populations is lacking. To dissect types brain...
We present an enhancer AAV toolbox for accessing and perturbing striatal cell types circuits. Best-in-class vectors were curated major neuron populations including medium spiny neurons (MSNs), direct indirect pathway MSNs, as well Sst-Chodl, Pvalb-Pthlh, cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes virus delivery, with diverse transgene cargos. Importantly, we provide detailed information necessary to achieve reliable...
The ability to imitate the vocalizations of other organisms, a trait known as vocal learning, is shared by only few including humans, where it subserves acquisition speech and language, 3 groups birds. In songbirds, learning requires coordinated activity set specialized brain nuclei referred song control system. Recent efforts have revealed some genes that are expressed in these nuclei, however thorough characterization transcriptional specializations this system still missing. We conducted...
How the evolution of complex behavioral traits is associated with emergence novel brain pathways largely unknown. Songbirds, like humans, learn vocalizations via tutor imitation and possess a specialized circuitry to support this behavior. In comprehensive in situ hybridization effort, we show that zebra finch vocal robust nucleus arcopallium (RA) shares numerous markers (e.g. SNCA, PVALB) adjacent dorsal intermediate (AId), an avian analog mammalian deep cortical layers involvement motor...
Diverse traits have evolved through cis-regulatory changes in genome sequence that influence the magnitude, timing and cell type-specificity of gene expression. Advances high-throughput sequencing regulatory genomics led to identification elements individual species, but these genomic regions remain difficult align across taxonomic orders due their lack conservation relative protein coding genes. The groundwork for tracing evolution is provided by recent assembly hundreds genomes, generation...
The memorization and production of song in songbirds share important parallels with the process speech acquisition humans. In songbirds, these processes are dependent on a group specialized telencephalic nuclei known as system: HVC (used proper name), RA (robust nucleus arcopallium), LMAN (lateral magnocellular nidopallium) striatal Area X. A recent study suggested that arcopallium Sayornis phoebe, non vocal learner suboscine species, contains some properties similar to those songbird RA,...
Abstract Vocal learning is a skilled motor behavior observed in several mammalian and avian species critical for human speech. While convergent gene expression patterns have highlighted similar primary striatal pathways vocal imitation songbirds humans, the extent of molecular circuit convergence remains unresolved. Here we profiled four principal song nuclei zebra finch (HVC, LMAN, RA, Area X) their surrounding brain regions using RNA-Seq compared them with specialized markers identified...