Neutral mutations

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

Given a large population of individuals, a considerable number of sequence variants can be found for a protein. These variants are a consequence of mutations in a gene (base substitutions in DNA) that have arisen naturally within the population. Gene mutations lead to mutant forms of the protein in which the amino acid sequence is altered at one or more positions. Many of these mutant forms are neutral in that the functional properties of the protein are unaffected by the amino acid substitution. Others may be nonfunctional (if loss of function is not lethal to the individual), and still others may display a range of aberrations between these two extremes. The severity of the effects on function depends on the nature of the amino acid substitution and its role in the protein. These conclusions are exemplified by the more than 300 human... 

Mutation is a stable, heritable change of a gene from one allele to another, which both creates and maintains genetic variability in populations. Most mutations adversely affect the survival and reproductive success of their bearers, but if the physical or biological environment changes, previously neutral or harmful alleles may become beneficial. Mutation rates typically are very low, but they are sufficient to create considerable genetic variation over many generations. 

Hall BG (1990) Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 126 5-16. 

Zhang PF, Bouma P, Park EJ, et al. A variable region 3 (V3) mutation determines a global neutralization phenotype and CD4-independent infectivity of a human immunodeficiency virus type 1 envelope associated with a broadly cross-reactive, primary virus-neutralizing antibody response. J Virol 2002 76(2) 644-655. 

Darwin was a pluralist. He was very careful to state that natural selection is not the only motor of evolutionary change. He invented the concept of sexual selection, the only addition to natural selection which evolutionary psychology theorists are prepared to include in their pantheon. We need not be Lamarckian to accept that other processes are at work. The existence of neutral mutations, founder effects, genetic drift, exaptations and adoptations (Dover, 2000) all enrich the picture. 

Cyan fluorescent proteins (CFPs) have blue-shifted excitation and emission spectra, because of the mutation Tyr66Trp inside the chromophore (Fig. 5.3C) [34], CFP fluorescence (Ex 435 nm/Em 474 nm) is less blue-shifted than for EBFP and CFP excitation is intermediate to the excitation of the neutral and anionic chromo-phores of avGFP [4], CFPs are widely used for dual-color imaging and FRET applications together with yellow fluorescent proteins (YFP, Section 3.6). 

In one series of experiments the cytochrome c oxidase mutations replaced acidic residues by neutral ones, and some of them were thus expected to alter the nature of binding of the protein to cytochrome c. From the pattern of dependence of the heme c to Cua electron-transfer rate constant on these mutations it was deduced that the binding of cytochrome c to cytochrome c oxidase is mediated by electrostatic interactions between four specific acidic residues on cytochrome c oxidase and lysines on cytochrome c. In another series of experiments, tryptophan 143 of cytochrome c oxidase was mutated to Phe or Ala. These mutations had an insignificant effect on the binding of the two proteins, but they dramatically reduced the rate constant for electron transfer from heme c to Cua- It was concluded that electron transfer from... 

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