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201.
Haag-Liautard C Dorris M Maside X Macaskill S Halligan DL Houle D Charlesworth B Keightley PD 《Nature》2007,445(7123):82-85
Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation (U) appears in theories of nucleotide divergence and polymorphism, the evolution of sex and recombination, and the evolutionary consequences of inbreeding. However, estimates of U based on changes in allozymes or DNA sequences and fitness traits are discordant. Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography. From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u among the three mutation-accumulation-line genotypes. By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila, we estimate that U is 1.2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction. 相似文献
202.
The genome of woodland strawberry (Fragaria vesca) 总被引:3,自引:0,他引:3
Shulaev V Sargent DJ Crowhurst RN Mockler TC Folkerts O Delcher AL Jaiswal P Mockaitis K Liston A Mane SP Burns P Davis TM Slovin JP Bassil N Hellens RP Evans C Harkins T Kodira C Desany B Crasta OR Jensen RV Allan AC Michael TP Setubal JC Celton JM Rees DJ Williams KP Holt SH Ruiz Rojas JJ Chatterjee M Liu B Silva H Meisel L Adato A Filichkin SA Troggio M Viola R Ashman TL Wang H Dharmawardhana P Elser J Raja R Priest HD Bryant DW Fox SE Givan SA Wilhelm LJ Naithani S Christoffels A Salama DY 《Nature genetics》2011,43(2):109-116
203.
It has been 15 years since we proposed the defective ribosomal product (DRiP) hypothesis to explain the rapid presentation
of viral peptides by MHC class I molecules on the surface of infected cells. Here, we review the evidence for the contribution
of DRiPs to antigen processing, pointing to the uncertainties regarding the physical nature of DRiPs, and emphasizing recent
findings suggesting that peptide generation is a specialized process involving compartmentalized translation. 相似文献
204.
de Bakker PI Burtt NP Graham RR Guiducci C Yelensky R Drake JA Bersaglieri T Penney KL Butler J Young S Onofrio RC Lyon HN Stram DO Haiman CA Freedman ML Zhu X Cooper R Groop L Kolonel LN Henderson BE Daly MJ Hirschhorn JN Altshuler D 《Nature genetics》2006,38(11):1298-1303
A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world. 相似文献
205.
Tsuji K Bandyopadhyay A Harfe BD Cox K Kakar S Gerstenfeld L Einhorn T Tabin CJ Rosen V 《Nature genetics》2006,38(12):1424-1429
Adult bones have a notable regenerative capacity. Over 40 years ago, an intrinsic activity capable of initiating this reparative response was found to reside within bone itself, and the term bone morphogenetic protein (BMP) was coined to describe the molecules responsible for it. A family of BMP proteins was subsequently identified, but no individual BMP has been shown to be the initiator of the endogenous bone repair response. Here we demonstrate that BMP2 is a necessary component of the signaling cascade that governs fracture repair. Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time. In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked. Although other osteogenic stimuli are still present in the limb skeleton of BMP2-deficient mice, they cannot compensate for the absence of BMP2. Collectively, our results identify BMP2 as an endogenous mediator necessary for fracture repair. 相似文献
206.
Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions 总被引:2,自引:2,他引:0
Louisa C. E. Windus Katie E. Lineburg Susan E. Scott Christina Claxton Alan Mackay-Sim Brian Key James A. St John 《Cellular and molecular life sciences : CMLS》2010,67(10):1735-1750
The growth and guidance of primary olfactory axons are partly attributed to the presence of olfactory ensheathing cells (OECs). However, little is understood about the differences between the subpopulations of OECs and what regulates their interactions. We used OEC-axon assays and determined that axons respond differently to peripheral and central OECs. We then further purified OECs from anatomically distinct regions of the olfactory bulb. Cell behaviour assays revealed that OECs from the olfactory bulb were a functionally heterogeneous population with distinct differences which is consistent with their proposed roles in vivo. We found that the heterogeneity was regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolished the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell–cell recognition. 相似文献
207.
208.
Parameshwaran K Buabeid MA Karuppagounder SS Uthayathas S Thiruchelvam K Shonesy B Dityatev A Escobar MC Dhanasekaran M Suppiramaniam V 《Cellular and molecular life sciences : CMLS》2012,69(5):829-841
In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of
neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted
when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure
has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular
mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral,
neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on
the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third
day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like
effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission,
and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in
protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845)
GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could
result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes. 相似文献
209.
210.