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71.
Orr HA 《Journal of theoretical biology》2003,220(2):241-247
I consider the adaptation of a DNA sequence when mutant fitnesses are drawn randomly from a probability distribution. I focus on "gradient" adaptation in which the population jumps to the best mutant sequence available at each substitution. Given a random starting point, I derive the distribution of the number of substitutions that occur during adaptive walks to a locally optimal sequence. I show that the mean walk length is a constant:L = e-1, where e approximately 2.72. I argue that this result represents a limit on what is possible under any form of adaptation. No adaptive algorithm on any fitness landscape can arrive at a local optimum in fewer than a mean of L = e-1 steps when starting from a random sequence. Put differently, evolution must try out at least e wild-type sequences during an average bout of adaptation. 相似文献
72.
Microtubules are long filamentous protein structures that randomly alternate between periods of elongation and shortening in a process termed dynamic instability. The average time a microtubule spends in an elongation phase, known as the catastrophe time, is regulated by the biochemical machinery of the cell throughout the cell cycle. In this light, observed changes in the catastrophe time near cellular boundaries (Brunner, D., and P. Nurse. 2000. Cell. 102:695-704; Komarova, Y.A., I.A. Vorobjev, and G.G. Borisy. 2002. J. Cell Sci. 115:3527-3539) may be attributed to regulatory effects of localized proteins. Here, we argue that the pushing force generated by a microtubule when growing against a cellular object may itself provide a regulatory mechanism of the catastrophe time. We observed an up to 20-fold, force-dependent decrease in the catastrophe time when microtubules grown from purified tubulin were polymerizing against microfabricated barriers. Comparison with catastrophe times for microtubules growing freely at different tubulin concentrations leads us to conclude that force reduces the catastrophe time only by limiting the rate of tubulin addition. 相似文献
73.
Statistical and biochemical studies of the genetic code have found evidence of nonrandom patterns in the distribution of
codon assignments. It has, for example, been shown that the code minimizes the effects of point mutation or mistranslation:
erroneous codons are either synonymous or code for an amino acid with chemical properties very similar to those of the one
that would have been present had the error not occurred. This work has suggested that the second base of codons is less efficient
in this respect, by about three orders of magnitude, than the first and third bases. These results are based on the assumption
that all forms of error at all bases are equally likely. We extend this work to investigate (1) the effect of weighting transition
errors differently from transversion errors and (2) the effect of weighting each base differently, depending on reported mistranslation
biases. We find that if the bias affects all codon positions equally, as might be expected were the code adapted to a mutational
environment with transition/transversion bias, then any reasonable transition/transversion bias increases the relative efficiency
of the second base by an order of magnitude. In addition, if we employ weightings to allow for biases in translation, then
only 1 in every million random alternative codes generated is more efficient than the natural code. We thus conclude not only
that the natural genetic code is extremely efficient at minimizing the effects of errors, but also that its structure reflects
biases in these errors, as might be expected were the code the product of selection.
Received: 25 July 1997 / Accepted: 9 January 1998 相似文献
74.
Catastrophe and social order 总被引:1,自引:1,他引:0
David W. Orr 《Human ecology: an interdisciplinary journal》1979,7(1):41-52
This paper presents three propositions. First, the author suggests that there is a growing potential for technologically induced catastophes. Second, our capacity to analyze technological risk is inhibited in part because: (1) we tend to confuse low-probability/low-consequence events with low-probability/high-consequence risks; (2) we seldom adopt a holistic approach to the analysis of risk; and (3) we tend to underestimate the effects of catastrophic events. The author further argues that existing control systems, including federal regulatory bodies, are inadequate. In the conclusion the author discusses difficulties likely to accompany the design and creation of risk control systems. 相似文献
75.
This paper proposes a class of estimators for estimating the finite population mean -Y of a study variate y using information on two auxiliary variates, one of which is positively and the other negatively correlated with the study variate y. An “asymptotically optimum estimator” (AOE) in the class is identified with its bias and mean square error formulae. It is observed that the proposed AOE is more efficient than Srivastava (1965), Srivastava (1974), Prasad (1989) and Gandge , Varghese , and Prabhu-Ajgaonkar (1993) estimators. 相似文献
76.
77.
XMAP215/TOGp family members and KinI kinesins are conserved microtubule (MT)-regulatory proteins, and have been viewed as possessing prominent antagonistic stabilizing/destabilizing activities that must be balanced. Here, interdependencies between TOGp and the KinI kinesin MCAK were analyzed in human leukemia cells. A system was established that permits inducible overexpression in homogeneous cell populations that simultaneously synthesize interfering short hairpin RNAs. We present evidence that the functional interplay of TOGp and MCAK proteins is manifested as three distinct phenotypes during the cell cycle. The first involves a role for TOGp in protecting spindle MTs from MCAK activity at the centrosome, which appears essential to prevent the formation of disorganized multipolar spindles. The second phenotype involves TOGp-dependent counteraction of excessive MCAK activity during mitosis, which recapitulates the previously established plus-end specific counteractive activities in vitro. The third involves an unexpected destabilization of the interphase MTs by overexpressed TOGp, a phenotype that requires endogenous MCAK. We hypothesize that TOGp-dependent prevention of MCAK-mediated spindle disorganization, as evidenced by depletion experiments, reflects a primary physiological role for TOGp in human somatic cells. 相似文献
78.
Quantitative analyses of animal motion are increasingly easy to conduct using simple video equipment and relatively inexpensive software packages. With careful use, such analytical tools have the potential to quantify differences in movement between individuals or species and to allow insights into the behavioral consequences of morphological differences between taxa. However, as with any other type of measurement, there are errors associated with kinematic measurements. Because normative kinematic data on human and nonhuman primate locomotion are used to model aspects of gait of fossil hominins, errors in the extant data influence the accuracy of fossil gait reconstructions. The principal goal of this paper is to illustrate the effect of camera speeds (frame rates) on kinematic measurement errors, and to demonstrate how these errors vary with subject size, movement velocity, and sample size. Kinematic data for human walking and running (240 Hz), as well as data for primate quadrupedal walking and running (180 Hz) were used as inputs for a simulation of the measurement errors associated with various linear and temporal kinematic variables. Measurement errors were shown to increase as camera speed, subject body size, and interval duration all decrease, and as movement velocity increases. These results have implications for the methods used to calculate subject velocity and suggest that using a moving marker to measure the linear displacements of the body is preferable to the use of a stationary marker. Finally, while slower camera speeds will always result in higher measurement errors than do faster camera speeds, this effect can be moderated to some extent by collecting sufficiently large samples of data. 相似文献
79.
Human solid tumors are believed to be caused by a sequence of genetic abnormalities arising in the tumor cells. The understanding of these sequences is extremely important for improving cancer treatment. Models for the occurrence of the abnormalities include linear structure and a recently proposed tree-based structure. In this paper we extend the pure oncogenetic tree model by introducing false positive and false negative observations. We state conditions sufficient for the reconstruction of the generating tree. As an example we analyze a comparative genomic hybridization data set and show that addition of the error model significantly improves the ability of the model to describe the data. 相似文献
80.
Benjamin Liou Wendy D. Haffey Kenneth D. Greis Gregory A. Grabowski 《The Journal of biological chemistry》2014,289(43):30063-30074
The acid β-glucosidase (glucocerbrosidase (GCase)) binding sequence to LIMP-2 (lysosomal integral membrane protein 2), the receptor for intracellular GCase trafficking to the lysosome, has been identified. Heterologous expression of deletion constructs, the available GCase crystal structures, and binding and co-localization of identified peptides or mutant GCases were used to identify and characterize a highly conserved 11-amino acid sequence, DSPIIVDITKD, within human GCase. The binding to LIMP-2 is not dependent upon a single amino acid, but the interactions of GCase with LIMP-2 are heavily influenced by Asp399 and the di-isoleucines, Ile402 and Ile403. A single alanine substitution at any of these decreases GCase binding to LIMP-2 and alters its pH-dependent binding as well as diminishing the trafficking of GCase to the lysosome and significantly increasing GCase secretion. Enterovirus 71 also binds to LIMP-2 (also known as SCARB2) on the external surface of the plasma membrane. However, the LIMP-2/SCARB2 binding sequences for enterovirus 71 and GCase are not similar, indicating that LIMP-2/SCARB2 may have multiple or overlapping binding sites with differing specificities. These findings have therapeutic implications for the production of GCase and the distribution of this enzyme that is delivered to various organs. 相似文献