Scholars@Duke
Craig Lowe

Craig Lowe

Assistant Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology

Selected Publications

Novelty versus innovation of gene regulatory elements in human evolution and disease.

Journal Article Curr Opin Genet Dev · November 25, 2024 It is not currently understood how much of human evolution is due to modifying existing functional elements in the genome versus forging novel elements from nonfunctional DNA. Many early experiments that aimed to assign genetic changes on the human lineage ... Full text Link to item Cite

Dysregulation of zebrin-II cell subtypes in the cerebellum is a shared feature across polyglutamine ataxia mouse models and patients.

Journal Article Sci Transl Med · November 6, 2024 Spinocerebellar ataxia type 7 (SCA7) is a genetic neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. Purkinje cells (PCs) are central to the pathology of ataxias, but their low abundance in the cerebellum underrepresents their trans ... Full text Link to item Cite

Complete sequencing of ape genomes.

Journal Article bioRxiv · October 5, 2024 We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy ... Full text Link to item Cite

Antibody-assisted selective isolation of Purkinje cell nuclei from mouse cerebellar tissue.

Journal Article Cell Rep Methods · July 15, 2024 We developed a method that utilizes fluorescent labeling of nuclear envelopes alongside cytometry sorting for the selective isolation of Purkinje cell (PC) nuclei. Beginning with SUN1 reporter mice, we GFP-tagged envelopes to confirm that PC nuclei could b ... Full text Link to item Cite

Human-specific genetics: new tools to explore the molecular and cellular basis of human evolution.

Journal Article Nat Rev Genet · October 2023 Our ancestors acquired morphological, cognitive and metabolic modifications that enabled humans to colonize diverse habitats, develop extraordinary technologies and reshape the biosphere. Understanding the genetic, developmental and molecular bases for the ... Full text Link to item Cite

Gonomics: uniting high performance and readability for genomics with Go.

Journal Article Bioinformatics · August 1, 2023 SUMMARY: Many existing software libraries for genomics require researchers to pick between competing considerations: the performance of compiled languages and the accessibility of interpreted languages. Go, a modern compiled language, provides an opportuni ... Full text Open Access Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection.

Journal Article Cell · November 23, 2022 The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ... Full text Link to item Cite

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

Journal Article Cell · November 23, 2022 Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes ... Full text Open Access Link to item Cite

Evolution of stickleback spines through independent cis-regulatory changes at HOXDB.

Journal Article Nat Ecol Evol · October 2022 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 in different fish genera to alter the length and number of ... Full text Link to item Cite

Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Journal Article Cell · February 7, 2019 Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first ... Full text Link to item Cite

Characterization of a Human-Specific Tandem Repeat Associated with Bipolar Disorder and Schizophrenia.

Journal Article Am J Hum Genet · September 6, 2018 Bipolar disorder (BD) and schizophrenia (SCZ) are highly heritable diseases that affect more than 3% of individuals worldwide. Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb ... Full text Link to item Cite

Detecting differential copy number variation between groups of samples.

Journal Article Genome Res · February 2018 We present a method to detect copy number variants (CNVs) that are differentially present between two groups of sequenced samples. We use a finite-state transducer where the emitted read depth is conditioned on the mappability and GC-content of all reads t ... Full text Open Access Link to item Cite

Feather development genes and associated regulatory innovation predate the origin of Dinosauria.

Journal Article Mol Biol Evol · January 2015 The evolution of avian feathers has recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics an ... Full text Open Access Link to item Cite

29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.

Journal Article PLoS One · 2012 Recent research supports the view that changes in gene regulation, as opposed to changes in the genes themselves, play a significant role in morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers ar ... Full text Open Access Link to item Cite

A high-resolution map of human evolutionary constraint using 29 mammals.

Journal Article Nature · October 12, 2011 The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, ... Full text Open Access Link to item Cite

The genome of the green anole lizard and a comparative analysis with birds and mammals.

Journal Article Nature · August 31, 2011 The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequence ... Full text Open Access Link to item Cite

Three periods of regulatory innovation during vertebrate evolution.

Journal Article Science · August 19, 2011 The gain, loss, and modification of gene regulatory elements may underlie a substantial proportion of phenotypic changes on animal lineages. To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of p ... Full text Open Access Link to item Cite

GREAT improves functional interpretation of cis-regulatory regions.

Journal Article Nat Biotechnol · May 2010 We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into ... Full text Open Access Link to item Cite

Endangered species hold clues to human evolution.

Journal Article J Hered · 2010 We report that 18 conserved, and by extension functional, elements in the human genome are the result of retroposon insertions that are evolving under purifying selection in mammals. We show evidence that 1 of the 18 elements regulates the expression of AS ... Full text Open Access Link to item Cite

Comparative genomics search for losses of long-established genes on the human lineage.

Journal Article PLoS Comput Biol · December 2007 Taking advantage of the complete genome sequences of several mammals, we developed a novel method to detect losses of well-established genes in the human genome through syntenic mapping of gene structures between the human, mouse, and dog genomes. Unlike m ... Full text Link to item Cite

Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53.

Journal Article Proc Natl Acad Sci U S A · November 20, 2007 The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not cl ... Full text Open Access Link to item Cite

Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.

Journal Article Proc Natl Acad Sci U S A · May 8, 2007 At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, fu ... Full text Open Access Link to item Cite

A distal enhancer and an ultraconserved exon are derived from a novel retroposon.

Journal Article Nature · May 4, 2006 Hundreds of highly conserved distal cis-regulatory elements have been characterized so far in vertebrate genomes. Many thousands more are predicted on the basis of comparative genomics. However, in stark contrast to the genes that they regulate, in inverte ... Full text Link to item Cite