Mutation, definition

Initially, it was assumed that the HlV-1 population is infinite, evolution is deterministic, and antiretroviral resistance development is definite (Coffin 1995). However, our research amongst others has demonstrated that the effective population size, defined as the average number of HIV variants that produces infectious progeny is relatively small (Leigh Brown 1997 Leigh Brown and Richman 1997 Nijhnis et al. 1998). This can be explained because the majority of virus particles that are produced harbor deleterious mutations resulting in noninfectious virus. Also limited target cell availability and inactivation of potentially infectious viruses by the host... 

B24. Beutler, E., Westwood, B., and Kuhl, W., Definition of the mutation of G6PD Wayne, G6PD Viangchan, G6PD Jammu, and G6PD LeJeune . Acta Haematol. 86,179-182 (1991). 

Almost all problems that require knowledge of free energies are naturally formulated or can be framed in terms of (1.15) or (1.16). Systems 0 and 1 may differ in several ways. For example, they may be characterized by different values of a macroscopic parameter, such as the temperature. Alternatively, they may be defined by two different Hamiltonians, 3%o and 3%, as is the case in studies of free energy changes upon point mutation of one or several amino acids in a protein. Finally, the definitions of 0 and 1 can be naturally extended to describe two different, well-defined macroscopic states of the same system. Then, Q0 is defined as ... 

Correlated mutation analysis does not yield a precise and exhaustive enumeration of all the interacting residues in a complex. Rather, tests have shown (177) that the result is a definition of the neighborhood of interacting regions. This makes the careful construction of explicit 3D models of GPCR homodimers, using the information derived... 

Ashby J, Tennant RW. 1990. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat Res 257 229-306. 

Comparison of mutation frequencies is made with the historical database. For definition of a positive result the same principles are recommended as for the mouse spot test (Selby and Olson, 1981). A minimum size of 18,000 offspring per group is recommended by those authors for definition of a negative result. 

While the results of this work are encouraging, it is clear that the structural definition of mutant proteins of this type is critical to development of rational interpretation of the results if for no other reason than that the structural perturbation introduced is presumably greater than for simple point mutations. Moreover, it would be particularly interesting to compare the functional properties of mutants compared in this manner in assays involving protein-protein reactions relevant to the species of cytochrome c on which the mutagenesis is based. For example, comparison of the activities of wild-type yeast cytochrome c with that of a loop-insertion mutant modelled on a photosynthetic cytochrome c in the reaction with the photosynthetic reaction center could help define the structural elements involved in the cytochrome c binding domain for the reaction center. 

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