John Maynard Smith

The hitch-hiking effect of a favourable gene

When a selectively favourable gene substitution occurs in a population, changes in gene frequencies will occur at closely linked loci. In the case of a neutral polymorphism, average heterozygosity will be reduced to an extent which varies with distance from the substituted locus. The aggregate effect of substitution on neutral polymorphism is estimated; in populations of total size 10 6 or more (and perhaps of 10 4 or more), this effect will be more important than that of random fixation. This may explain why the extent of polymorphism in natural populations does not vary as much as one would expect from a consideration of the equilibrium between mutation and random fixation in populations of different sizes. For a selectively maintained polymorphism at a linked locus, this process will only be important in the long run if it leads to complete fixation. If the selective coefficients at the linked locus are small compared to those at the substituted locus, it is shown that the probability of complete fixation at the linked locus is approximately exp (− Nc ), where c is the recombinant fraction and N the population size. It follows that in a large population a selective substitution can occur in a cistron without eliminating a selectively maintained polymorphism in the same cistron.

THE LOGIC OF ASYMMETRIC CONTESTS

Abstract A theoretical analysis is made of the evolution of behavioural strategies in contest situations. It is assumed that behaviour will evolve so as to maximize individual fitness. If so, a population will evolve an ‘evolutionarily stable strategy’, or ESS, which can be defined as a strategy such that, if all members of a population adopt it, no ‘mutant’ strategy can do better. A number of simple models of contest situations are analysed from this point of view. It is concluded that in ‘symmetric’ contests the ESS is likely to be a ‘mixed’ strategy; that is, either the population will be genetically polymorphic or individuals will be behaviourally variable. Most real contests are probably asymmetric, either in pay-off to the contestants, or in size or weapons, or in some ‘uncorrelated’ fashion; i.e. in a fashion which does not substantially bias either the pay-offs or the likely outcome of an escalated contest. An example of an uncorrelated asymmetry is that between the ‘discoverer’ of a resource and a ‘late-comer’. It is shown that the ESS in asymmetric contests will usually be to permit the asymmetric cue to settle the contest without escalation. Escalated contests will, however, occur if information to the contestants about the asymmetry is imperfect.

Analyzing the mosaic structure of genes.

SummarySome genes in prokaryotes consist of a mosaic of regions derived from different ancestors by horizontal gene transfer. A method is described for demonstrating the statistical significance of such mosaic structure and for locating the crossover points separating different regions.

Evolution of genetic redundancy

Genetic redundancy means that two or more genes are performing the same function and that inactivation of one of these genes has little or no effect on the biological phenotype. Redundancy seems to be widespread in genomes of higher organisms. Examples of apparently redundant genes come from numerous studies of developmental biology, immunology,, neurobiology, and the cell cycle,. Yet there is a problem: genes encoding functional proteins must be under selection pressure. If a gene was truly redundant then it would not be protected against the accumulation of deleterious mutations. A widespread view is therefore that such redundancy cannot be evolutionarily stable. Here we develop a simple genetic model to analyse selection pressures acting on redundant genes. We present four cases that can explain why genetic redundancy is common. In three cases, redundancy is even evolutionarily stable. Our theory provides a framework for exploring the evolution of genetic organization.

Natural selection and the concept of a protein space.

SALISBURY1 has argued that there is an apparent contradiction between two fundamental concepts of biology—the belief that the gene is a unique sequence of nucleotides whose function it is to determine the sequence of amino-acids in a protein, and the theory of evolution by natural selection. In brief, he calculated that the number of possible amino-acid sequences is greater by many orders of magnitude than the number of proteins which could have existed on Earth since the origin of life, and hence that functionally effective proteins have a vanishingly small chance of arising by mutation. Natural selection is therefore ineffective because it lacks the essential raw material—favourable mutations.

The Concept of Information in Biology

It is clear from these quotations that there is something to talk about. I shall be concerned only with the use of information concepts in genetics, evolution and development, and not in neurobiology, which I am not competent to discuss.

Population structure and evolutionary dynamics of pathogenic bacteria

Evidence concerning the significance of recombination within natural bacterial populations has historically come from two main sources: multilocus enzyme electrophoresis (MLEE) and nucleotide sequence data. Here we discuss evidence from a third method, multilocus sequence typing (MLST), which is a development of MLEE based on nucleotide sequencing that combines the advantages of both approaches. MLST has confirmed both the existence of clones and the high rates of recombination for several bacterial pathogens. The data are consistent with “epidemic” population structures, where clones are superimposed upon a backdrop of frequent recombination, thus, in the short term, resisting the homogenising effect of recombination. The nature of the selective advantage of clones, however, and how this advantage relates to virulence are unclear. The current evidence also has broader implications concerning bacterial species definition, the management of antibiotic‐resistant bacteria and the assessment of the dangers of releasing genetically modified organisms into the environment. BioEssays 22:1115–1122, 2000.

Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species.

SummaryThe two pathogenic species of Neisseria, N. meningitidis and N. gonorrhoeae, have evolved resistance to penicillin by alterations in chromosomal genes encoding the high molecular weight penicillin-binding proteins, or PBPs. The PBP 2 gene (penA) has been sequenced from over 20 Neisseria isolates, including susceptible and resistant strains of the two pathogenic species, and five human commensal species. The genes from penicillin-susceptible strains of N. meningitidis and N. gonorrhoeae are very uniform, whereas those from penicillin-resistant strains consist of a mosaic of regions resembling those in susceptible strains of the same species, interspersed with regions resembling those in one, or in some cases, two of the commensal species. The mosaic structure is interpreted as having arisen from the horizontal transfer, by genetic transformation, of blocks of DNA, usually of a few hundred base pairs. The commensal species identified as donors in these interspecies recombinational events (N. flavescens and N. cinerea) are intrinsically more resistant to penicillin than typical isolates of the pathogenic species. Transformation has apparently provided N. meningitidis and N. gonorrhoeae with a mechanism by which they can obtain increased resistance to penicillin by replacing their penA genes (or the relevant parts of them) with the penA genes of related species that fortuitously produce forms of PBP 2 that are less susceptible to inhibition by the antibiotic. The ends of the diverged blocks of DNA in the penA genes of different penicillin-resistant strains are located at the same position more often than would be the case if they represent independent crossovers at random points along the gene. Some of these common crossover points may represent common ancestry, but reasons are given for thinking that some may represent independent events occurring at recombinational hotspots.

How clonal are human mitochondria

Phylogenetic trees constructed using human mitochondrial sequences contain a large number of homoplasies. These are due either to repeated mutation or to recombination between mitochondrial lineages. We show that a tree constructed using synonymous variation in the protein coding sequences of 29 largely complete human mitochondrial molecules contains 22 homoplasies at 32 phylogenetically informative sites. This level of homoplasy is very unlikely if inheritance is clonal, even if we take into account base composition bias. There must either be ‘hypervariable’ sites or recombination between mitochondria. We present evidence which suggests that hypervariable sites do not exist in our data. It therefore seems likely that recombination has occurred between mitochondrial lineages in humans.

Sexual selection and the handicap principle

The theory that sexual selection may cause females to select males with a handicap is analysed by means of a simple model. It is concluded that the proposed mechanism does not produce the results claimed for it, even allowing for sex-limited inheritance of the handicap.