A5034156995- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Sperm and Testicular Function
- Sexual Differentiation and Disorders
- Neurobiology and Insect Physiology Research
- DNA Repair Mechanisms
- Genomics and Phylogenetic Studies
- Invertebrate Immune Response Mechanisms
- Insect symbiosis and bacterial influences
- Genetic diversity and population structure
- Cancer Mechanisms and Therapy
- Genetic Mapping and Diversity in Plants and Animals
- Enzyme Structure and Function
- Surfactants and Colloidal Systems
- Evolution and Genetic Dynamics
- Metabolism, Diabetes, and Cancer
- Advanced Control Systems Optimization
- Heat shock proteins research
- Animal Behavior and Reproduction
- Cancer, Hypoxia, and Metabolism
- Erosion and Abrasive Machining
- Carbohydrate Chemistry and Synthesis
University of Michigan
2015-2025
Michigan United
2024
Whitehead Institute for Biomedical Research
2008-2015
Cornell University
2004-2014
Massachusetts Institute of Technology
2008-2010
University of Cambridge
2001
Shewanella oneidensis is an important model organism for bioremediation studies because of its diverse respiratory capabilities, conferred in part by multicomponent, branched electron transport systems. Here we report the sequencing S. genome, which consists a 4,969,803–base pair circular chromosome with 4,758 predicted protein-encoding open reading frames (CDS) and 161,613–base plasmid 173 CDSs. We identified first lambda-like phage, providing potential tool further genome engineering....
On ejaculation, sperm become coated with proteins secreted by the male accessory sex glands. In bull, these consist predominantly of bovine seminal plasma family (BSPs): PDC-109 (BSP-A1/-A2), BSP-A3, and BSP-30-kDa. plays a role in forming an oviductal reservoir enabling to bind epithelium. Because has high sequence identity other BSPs, we tested BSP-A3 BSP-30-kDa for capacity each increased binding epididymal epithelium were as effective competitively inhibiting ejaculated sperm. extends...
Abstract Drosophila melanogaster males transfer seminal fluid proteins along with sperm during mating. Among these proteins, ACPs (Accessory gland proteins) from the male's accessory induce behavioral, physiological, and life span reduction in mated females mediate storage utilization. A previous evolutionary EST screen D. simulans identified partial cDNAs for 57 new candidate ACPs. Here we report annotation confirmation of corresponding Acp genes melanogaster. Of previously reported...
The chromosomal program of meiotic prophase, comprising events such as laying down cohesins, synapsis between homologs, and homologous recombination, must be preceded enabled by the regulated induction prophase genes. This gene regulatory is poorly understood, particularly in organisms with a segregated germline. We characterized it occurs mouse fetal ovary. By profiling expression ovary mutants whole tissue single-cell techniques, we identified 104 genes expressed specifically pre-meiotic...
The house mouse X and Y chromosomes have recently acquired multicopy, rapidly evolving gene families representing an evolutionary arms race. This race between proteins encoded by X-linked Slxl1 / Slx Y-linked Sly can distort offspring sex ratio, but how these compete remains unknown. Here, we report in a protein family–specific dose-dependent manner using yeast. Specifically, SLXL1 competes with SLY1 SLY2 for binding to the Spindlin SPIN1. Similarly, SLX SSTY2. These competitions are driven...
The constituents of seminal fluid are a complex mixture proteins and other molecules, most whose functions have yet to be determined many which rapidly evolving. As step in elucidating the roles these exposing potential functional similarities hidden by their rapid evolution, we performed comparative structural modeling on 28 52 predicted produced Drosophila melanogaster male accessory gland. Each model was characterized defining residues likely important for structure function. Comparisons...
In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some proteins may provide protective functions to females, such as antimicrobial activity and/or stimulation gene expression levels, while others appear have negative effects, contributing a "cost mating." To identify that could participate in these phenomena, we used systemic ectopic screen test effects on unmated females normally produced by male accessory gland (Acps). Of 21...
Internally fertilizing organisms transfer a complex assortment of seminal fluid proteins, substantial fraction which are proteolysis regulators. In mammals, some protease inhibitors have been implicated in male infertility and these same molecular classes also found Drosophila fluid. Here, we tested the reproductive functions melanogaster inhibitor Acp62F by generating precise deletion gene. We did not detect nonredundant function for modulating egg laying, fertility, remating frequency, or...
Megabase-sized, complex, repetitive regions of genomes are poorly studied, due to the technical and computational challenges inherent both assembling precise reference sequences accurately assessing structural variation across contiguous megabase DNA regions. Here we describe a strategy overcome these challenges, CISMR (CRISPR-mediated isolation specific megabase-sized genome), which enables us perform targeted segments genome. Direct sequencing purified can have >100-fold enrichment target...
Abstract Mendelian genetics posits equal transmission of alleles, but selfish alleles can bias the large genomic regions or entire chromosomes 1–4 . One long-standing question is how evolves to encompass regions. Mus musculus (house mouse) t -haplotypes exhibit up 99% from heterozygous males 5–14 and harbor 9–14 genetically linked inversions spanning proximal half chromosome 17 15–20 Here, by generating a high-quality, single-haplotype assembly - haplotype, we reveal evolution eight...
Drosophila melanogaster originated in tropical Africa but has achieved a cosmopolitan distribution association with human habitation. Cosmopolitan populations of D. are known to have reduced genetic variation, particularly on the X chromosome. However, relative importance population bottlenecks and selective sweeps explaining this reduction is uncertain. We surveyed variation at 31 microsatellites across 330-kb section chromosome located between white kirre genes. Two linked clusters loci...
Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH pyruvate. As such, it has been identified as a gene interest obesity, type 2 diabetes, array epithelial cancers, with most work being performed vitro . The current standard model for ME1 loss vivo is the spontaneous Mod-1 null allele, which produces canonically inactive form ME1. Herein, we describe two new genetically engineered mouse models exhibiting at dynamic...
Our approach to fold recognition for the fourth critical assessment of techniques protein structure prediction (CASP4) experiment involved use FUGUE sequence-structure homology program (http://www-cryst.bioc.cam.ac.uk/fugue), followed by model building. We treat models as hypotheses and examine these determine whether they explain available data. method depends heavily on environment-specific substitution tables derived from our database structural alignments homologous proteins (HOMSTRAD,...
Large (>10 kb), nearly identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence X-Y recombination. It is unclear whether X-palindromes, which can freely recombine females, conversion and, if so, at what rate. We generated high-quality assemblies Mus molossinus and M. spretus X-palindromic regions...
Large (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families (≥2 copies) expressed exclusively in post-meiotic testicular germ cells, a time when most single-copy sex-linked genes transcriptionally repressed. This observation led to the hypothesis that structures or having ≥2 copies enable expression. We tested hypotheses by using CRISPR precisely engineer large (10's of inversions and deletions X-chromosome palindrome arms...
Abstract Mouse sex chromosomes are enriched for co-amplified gene families, present in tens to hundreds of copies. Co-amplification Slx/Slxl1 on the X chromosome and Sly Y involved dose-dependent meiotic drive, however role other genes remains poorly understood. Here we demonstrate that family chromosome, Srsx, along with two additional partial annotations, is actually part a larger transcription unit, which name Laidx. Laidx harbored 229 kb amplicon represents ancestral state as compared...
Abstract Reproductive isolation is a fundamental step in speciation. While sex chromosomes have been linked to reproductive many model systems, including hominids, genetic studies of the contribution chromosome loci speciation for natural populations are relatively sparse. Natural hybrid zones can help identify genomic regions contributing isolation, like incompatibility loci, since these exhibit reduced introgression between parental species. Here, we use primate zone (Alouatta palliata ×...
The mammalian X and Y chromosomes evolved from an ordinary pair of autosomes that existed in a reptilian ancestor probably relied on temperature-dependent sex determination, as crocodiles today. Independently concurrently, the avian Z W (ZZ males, ZW females) different was present same ancestor. Both XY have emerged with specialized disproportionate roles germ cell development. These specializations are best understood only now being appreciated pair. To reconstruct better understand...
Abstract The house mouse X and Y chromosomes have recently acquired high copy number, rapidly evolving gene families representing an evolutionary arms race. This race between proteins encoded by X-linked Slxl1 / Slx Y-linked Sly can distort male offspring sex ratio, but how these compete remains unknown. Here, we report in a protein family-specific dose-dependent manner using yeast. Specifically, SLXL1 competes with SLY1 SLY2 for binding to the Spindlin SPIN1. Similarly, SLX SSTY2. These...