Point beneficial mutation

Fig. 4. DNA shuffling method [10,35]. Related genes with different beneficial mutations (black dots) are randomly fragmented with DNasel. During reassembly of fragments recombination occurs yielding in progeny genes with improved positive mutations which can serve as starting points for another round of mutation and recombination...

Random point mutagenesis None Exhaustive No multiple simultaneous mutations requires multiple rounds to accumulate beneficial mutations... 

Sorcin is associated with the development of multidrug resistances in leukemia and other cancels. Sorcin is also able to improve cardiac contractility independently of (3-adienergic stimulation and may prove beneficial in treatment of heart failure. A point mutation in sorcin causes familial hypertrophic cardiomyopathy. 

The realization that one could screen or select beneficial point mutations or recombinations and discard deleterious ones, thus mimicking sexual recombination, spawned the field of directed evolution. 

A breakthrough was achieved by recognizing that the process of natural selection can be harnessed to evolve effective enzymes in artificial circumstances. In directed evolution the processes of natural evolution are accelerated in a test tube in order to select proteins with the desired properties. The realization that one could screen or select beneficial point mutations or recombinations and discard deleterious ones, thus mimicking sexual recombination, spawned the field of directed evolution. 

The benefit of recombination is twofold it combines good mutations and searches more sequence space in a meaningful way. Recombination is most beneficial when the number of mutants that can be screened is limited and the landscape is of an intermediate ruggedness. The structure of schema in proteins leads to the conclusion that many cut points are required. The number of parents and their sequence identity are determined by the balance between exploration and exploitation. Many disparate parents can explore more space, but at the risk of losing information. 

DNA shuffling improves the search of local fold space via a random yet correlated combination of homologous coding fragments that contain limited numbers of beneficial amino acid substitutions. As in experimental evolutions (Stemmer, 1994 Crameri et al., 1998 Zhang et al, 1997 Moore et al, 1997), the simulated shuffling improved protein function significantly better than did point mutation alone (see Table III and Fig. 6b). However, local... 

In focused mutagenesis experiments, the challenge is to identify the residues where mutagenesis is likely to be beneficial. Indeed, many successful directed evolution experiments show that mutations occur in regions that would be hard or impossible to predict (and difficull to explain that they do), even when a high-resolution structure and much information about the enzyme is available 14, 98-1001. One possibility is to make use of knowledge gained from early rounds of random point... 

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