Showing 61 - 70 of 257 Items
Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages
Date: 2015-12-29
Creator: Michael F. Palopoli, Daniel J. Fergus, Samuel Minot, Dorothy T. Pei, W. Brian, Simison, Iria Fernandez-Silva, Megan S. Thoemmes, Robert R. Dunn, Michelle Trautwein
Access: Open access
- Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement.
Fgf signaling is required for zebrafish tooth development
Date: 2004-10-01
Creator: William R. Jackman, Bruce W. Draper, David W. Stock
Access: Open access
- We have investigated fibroblast growth factor (FGF) signaling during the development of the zebrafish pharyngeal dentition with the goal of uncovering novel roles for FGFs in tooth development as well as phylogenetic and topographic diversity in the tooth developmental pathway. We found that the tooth-related expression of several zebrafish genes is similar to that of their mouse orthologs, including both epithelial and mesenchymal markers. Additionally, significant differences in gene expression between zebrafish and mouse teeth are indicated by the apparent lack of fgf8 and pax9 expression in zebrafish tooth germs. FGF receptor inhibition with SU5402 at 32 h blocked dental epithelial morphogenesis and tooth mineralization. While the pharyngeal epithelium remained intact as judged by normal pitx2 expression, not only was the mesenchymal expression of lhx6 and lhx7 eliminated as expected from mouse studies, but the epithelial expression of dlx2a, dlx2b, fgf3, and fgf4 was as well. This latter result provides novel evidence that the dental epithelium is a target of FGF signaling. However, the failure of SU5402 to block localized expression of pitx2 suggests that the earliest steps of tooth initiation are FGF-independent. Investigations of specific FGF ligands with morpholino antisense oligonucleotides revealed only a mild tooth shape phenotype following fgf4 knockdown, while fgf8 inhibition revealed only a subtle down-regulation of dental dlx2b expression with no apparent effect on tooth morphology. Our results suggest redundant FGF signals target the dental epithelium and together are required for dental morphogenesis. Further work will be required to elucidate the nature of these signals, particularly with respect to their origins and whether they act through the mesenchyme. © 2004 Elsevier Inc. All rights reserved.
Two modes of transvection at the eyes absent gene of Drosophila demonstrate plasticity in transcriptional regulatory interactions in cis and in trans
Date: 2019-01-01
Creator: Katherine Tian, Rachel E. Henderson, Reyna Parker, Alexia Brown, Justine E., Johnson, Jack R. Bateman
Access: Open access
- For many genes, proper gene expression requires coordinated and dynamic interactions between multiple regulatory elements, each of which can either promote or silence transcription. In Drosophila, the complexity of the regulatory landscape is further complicated by the tight physical pairing of homologous chromosomes, which can permit regulatory elements to interact in trans, a phenomenon known as transvection. To better understand how gene expression can be programmed through cis- and trans-regulatory interactions, we analyzed transvection effects for a collection of alleles of the eyes absent (eya) gene. We find that trans-activation of a promoter by the eya eye-specific enhancers is broadly supported in many allelic backgrounds, and that the availability of an enhancer to act in trans can be predicted based on the molecular lesion of an eya allele. Furthermore, by manipulating promoter availability in cis and in trans, we demonstrate that the eye-specific enhancers of eya show plasticity in their promoter preference between two different transcriptional start sites, which depends on promoter competition between the two potential targets. Finally, we show that certain alleles of eya demonstrate pairing-sensitive silencing resulting from trans-interactions between Polycomb Response Elements (PREs), and genetic and genomic data support a general role for PcG proteins in mediating transcriptional silencing at eya. Overall, our data highlight how eya gene regulation relies upon a complex but plastic interplay between multiple enhancers, promoters, and PREs.
Sutural loosening and skeletal flexibility during growth: Determination of drop-like shapes in sea urchins
Date: 2002-02-07
Creator: Amy S. Johnson, Olaf Ellers, Jim Lemire, Melissa Minor, Holly A., Leddy
Access: Open access
- The shape of sea urchins may be determined mechanically by patterns of force analogous to those that determine the shape of a water droplet. This mechanical analogy implies skeletal flexibility at the time of growth. Although comprised of many rigid calcite plates, sutural collagenous ligaments could confer such flexibility if the sutures between plates loosened and acted as joints at the time of growth. We present experimental evidence of such flexibility associated with weight gain and growth. Over 13-, 4-, and 2-week periods, fed urchins (Strongylocentrotus droebachiensis) gained weight and developed looser sutures than unfed urchins that maintained or lost weight. Further, skeletons of fed urchins force-relaxed more than did those of unfed urchins and urchins with loose sutures force-relaxed more than those with tight sutures. Urchins (Strongylocentrotus franciscanus) fed for two and a half weeks, gained weight, also had looser skeletons and deposited calcite at sutural margins, whereas unfed ones did not. In field populations of S. droebachiensis the percentage having loose sutures varied with urchin diameter and reflected their size-specific growth rate. The association between feeding, weight gain, calcite deposition, force relaxation and sutural looseness supports the hypothesis that urchins deform flexibly while growing, thus determining their drop-like shapes.
Rapid evolution of a coadapted gene complex: Evidence from the segregation Distorter (SD) system of meiotic drive in Drosophila melanogaster
Date: 1996-09-11
Creator: Michael F. Palopoli, Chung I. Wu
Access: Open access
- Segregation Distorter (SD) is a system of meiotic drive found in natural populations of Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homologue (SD+) produce predominantly SD- bearing sperm. The coadapted gene complex responsible for this transmission advantage spans the second chromosome centromere, consisting of three major and several minor interacting loci. To investigate the evolutionary history of this system, we surveyed levels of polymorphism and divergence at six genes that together encompass this pericentromeric region and span seven map units. Interestingly, there was no discernible divergence between SD and SD1 chromosomes for any of these molecular markers. Furthermore, SD chromosomes harbored much less polymorphism than did SD+ chromosomes. The results suggest that the SD system evolved recently, swept to appreciable frequencies worldwide, and carried with it the entire second chromosome centromeric region (roughly 10% of the genome). Despite its well-documented genetic complexity, this coadapted systems appears to have evolved on a time scale that is much shorter than can be gauge using nucleotide substitution data. Finally, the large genomic region hitchhiking with SD indicates that a multilocus, epistatically selected could affect the levels of DNA polymorphism observed in regions of reduced recombination.
Requirement for pectin methyl esterase and preference for fragmented over native pectins for wall-associated kinase-activated, EDS1/PAD4-dependent stress response in arabidopsis
Date: 2014-07-04
Creator: Bruce D. Kohorn, Susan L. Kohorn, Nicholas J. Saba, Victoriano Meco Martinez
Access: Open access
- Background: The wall-associated kinases (WAKs) serve as pectin receptors. Results: A pectin methyl esterase and two transcription factor mutants suppress a dominant WAK allele. Conclusion: De-esterification of pectin is required for WAK activation though EDS1 and PAD4. Significance: The results provide a mechanism for the state of pectins to activate two different pathways. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Intron Size Correlates Positively with Recombination Rate in Caenorhabditis elegans
Date: 2004-03-01
Creator: Anuphap Prachumwat, Laura DeVincentis, Michael F. Palopoli
Access: Open access
- A negative correlation between intron size and recombination rate has been reported for the Drosophila melanogaster and human genomes. Population-genetic models suggest that this pattern could be caused by an interaction between recombination rate and the efficacy of natural selection. To test this idea, we examined variation in intron size and recombination rate across the genome of the nematode Caenorhabditis elegans. Interestingly, we found that intron size correlated positively with recombination rate in this species.
Molecular basis of the copulatory plug polymorphism in Caenorhabditis elegans
Date: 2008-08-21
Creator: Michael F. Palopoli, Matthew V. Rockman, Aye TinMaung, Camden Ramsay, Stephen, Curwen, Andrea Aduna, Jason Laurita, Leonid Kruglyak
Access: Open access
- Heritable variation is the raw material for evolutionary change, and understanding its genetic basis is one of the central problems in modern biology. We investigated the genetic basis of a classic phenotypic dimorphism in the nematode Caenorhabditis elegans. Males from many natural isolates deposit a copulatory plug after mating, whereas males from other natural isolates-including the standard wild-type strain (N2 Bristol) that is used in most research laboratories-do not deposit plugs. The copulatory plug is a gelatinous mass that covers the hermaphrodite vulva, and its deposition decreases the mating success of subsequent males. We show that the plugging polymorphism results from the insertion of a retrotransposon into an exon of a novel mucin-like gene, plg-1, whose product is a major structural component of the copulatory plug. The gene is expressed in a subset of secretory cells of the male somatic gonad, and its loss has no evident effects beyond the loss of male mate-guarding. Although C. elegans descends from an obligate-outcrossing, male?female ancestor, it occurs primarily as self-fertilizing hermaphrodites. The reduced selection on male-male competition associated with the origin of hermaphroditism may have permitted the global spread of a loss-of-function mutation with restricted pleiotropy. ©2008 Macmillan Publishers Limited. All rights reserved.
Assessing parameters influencing interhomolog proximity of paired homologous chromosomes in Drosophila This record is embargoed.
- Embargo End Date: 2026-05-20
Date: 2021-01-01
Creator: Molly Margaret Moore
Access: Embargoed
Probing the mechanism of recognition of ssDNA by the Cdc13-DBD
Date: 2008-03-01
Creator: Aimee M. Eldridge, Deborah S. Wuttke
Access: Open access
- The Saccharomyces cerevisiae protein Cdc13 tightly and specifically binds the conserved G-rich single-stranded overhang at telomeres and plays an essential role in telomere end-protection and length regulation. The 200 residue DNA-binding domain of Cdc13 (Cdc13-DBD) binds an 11mer single-stranded representative of the yeast telomeric sequence [Tel11, d(GTGTGGGTGTG)] with a 3 pM affinity and specificity for three bases (underlined) at the 5′ end. The structure of the Cdc13-DBD bound to Tel11 revealed a large, predominantly aromatic protein interface with several unusual features. The DNA adopts an irregular, extended structure, and the binding interface includes a long (∼30 amino acids) structured loop between strands β2-β3 (L2-3) of an OB-fold. To investigate the mechanism of ssDNA binding, we studied the free and bound states of Cdc13-DBD using NMR spectroscopy. Chemical shift changes indicate that the basic topology of the domain, including L2-3, is essentially intact in the free state. Changes in slow and intermediate time scale dynamics, however, occur in L2-3, while conformational changes distant from the DNA interface suggest an induced fit mechanism for binding in the 'hot spot' for binding affinity and specificity. These data point to an overall binding mechanism well adapted to the heterogeneous nature of yeast telomeres. © 2008 The Author(s).