Neutral drift

II. Polymorphism versus Mutation—Neutral Drift versus Selection. 412... 

In a cooperative world, both Pavlovians and Generous Tit For Tat players do better than Tit For Tat, because they are immune to errors. Pavlov has an additional advantage it ensures that the population cannot be subverted by unconditional cooperators. Indeed, after a mistaken defection, Pavlov will not resume cooperation, but blithely continue to exploit the sucker. This is important, since otherwise neutral drift will cause unconditional cooperators to spread and thus soften up the population to such an extent that it loses its power to retaliate against exploiters. 

Emerging Methods in Directed Evolution Neutral Drift and Indels... 

Gupta, R.D. and Tawfik, D.S., Directed enzyme evolution via small and effective neutral drift libraries. Nat. Methods, 2008, 5, 939-942. 

The period when neutral drift dominates over adaptive evolution is called an epoch. If the fitness is plotted versus time, an epoch is a flat period showing no fitness improvement (Fig. 19). If a population becomes trapped at a suboptimal peak, it can remain trapped for a long time because it requires a specific series of mutations to escape the peak (Fontana et al., 1989). The time that a population remains trapped is longer for larger peaks. Neutrality helps the evolving population to overcome fitness barriers so that the highest fitness achieved by evolution increases with the size of the neutral network, as more sequence space can be explored (Newman and Engelhardt, 1998). 

To discover new fitness peaks, the neutral network must be sufficiently extended, allowing neutral drift to effectively sample sequence space. A neutral network can be characterized by a mean fraction of neutral neighbors A (Reidys et al., 1997). If A exceeds a threshold A,., then the network is connected and dense, making it more likely the network percolates through sequence space. If A < Ac, the networks are partitioned into components. Using random graph theory, the threshold is derived analytically as... 

Dover underlined that there is no rigid one-to-one relationship between evolutionary mechanisms and environmental processes, but noticed nonetheless that a certain correspondence does exist. He concluded therefore that adaptation is the normal result of natural selection just as exaptation is characteristic of neutral drift, and adoptation is typical of molecular drive. To our purposes, what matters is that we can indeed speak of three mechanisms of evolution the first two are natural selection and neutral drift, while the third mechanism can be called either genomic flux or molecular drive. 

Fig. 5. Tandem quadrupole acceleration-deceleration mass spectrometer for NRMS studies. A - ion source B - quadrupole mass analyzer C - ion acceleration lens D - neutralization cell E - neutral drift region F - reionization cell G - ion deceleration lens H - energy filter I - quadrupole mass analyzer J - off-axis ion detector K - laser optics L - Ar-ion laser. Inset shows the drift region where residual precursor ions are reflected and the neutral beam overlaps with the laser beam...

Two or more genotypes are neutral in evolution when the selection constraint is unable to distinguish between them. Early sequence comparison data [6] apparently confirmed Motoo Kimura s idea of neutral drift in population genetics [5]. Accordingly, many different genotypes could give rise to the same phenotype, and depending on the conditions, different phenotypes can share the same fitness value. Direct evidence for neutral evolution under controlled conditions came only two years ago Se-... 

Figure 8 Neutral drift may allow a protein with a certain fold in the red region to access a region in which sequences can adopt the fold of both the red and blue regions, and then to cross into the blue region in which a different fold is found. Reproduced with permission from R. A. Goldstein, Curr. Opin. Struct Biol. 2008, 18, 170-177.

In every enzyme family and superfamily, there are invariant residues that are required to maintain structure and/or function. However, for the majority of the residues, considerable variability is tolerated enzymes with <30% sequence identity often have very similar structures and identical functions. Such sequence divergence occurs by neutral drift, a process by which mutations that do not affect the fitness of the organism accumulate over long periods of time. 

The effects of neutral drift on promiscuous activities were explored in variants of bacteria P450 BM3 by Bloom etal Variants generated by error-prone PCR were screened to insure that they retained the ability to hydroxylate the substrate 12- -nitrophenoxydodecanoic acid at a level at least 75% that of the parental enzyme. Figure 16 shows the variability in the activity of 34 variants toward 12- -nitrophenoxydodecanoic acid and five alternative substrates. Even within a relatively short mutational distance of the parental enzyme, increases or decreases in activity toward various promiscuous substrates of up to fourfold were found. 

The divergence prior to duplication model is strongly supported by the notion of neutral networks. Theoretical, computational, and experimental works indicate that a drift under selection to maintain the existing function and structure (a neutral drift ) can increase the potential for adaptation (see Means and Bender , Smith, Nei, and Wroe and references therein). The existence of this latent pleiotropy - a... 

Recent laboratory experiments followed the notion of a neutral drift by placing an enzyme under mutation and selection to maintain its native function. The data provide empirical evidence in support of the hypothesis that neutrality enables the formation of latent changes, or latent adaptation . It was found ° that latent evolutionary potentials are indeed very frequent within a neutral set of related enzyme mutants, and that these potentials are most often seen as changes in specificity for one or more promiscuous substrates. 

Figure 8 Schematic representation of a putative neutral network of an enzyme. The scheme is based on the results of a neutral drift of serum paraoxonase (PON1) performed in the laboratory, and PON1 mutants identified in various directed evolution experiments. The mutations of neutral variants with significantly altered phenotypes are noted.

In an ion mobility spectrometer, analyte ions are moved by an applied electric field along a tube, where the ions experience multiple collisions with neutral drift gas molecules. Ion mobility spectrometry offers milliseconds-fast analysis time, simple operation and maintenance, low cost instrumentation, and portability. Ion mobility spectrometry is now the method of choice in... 

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