Search PubMed⌕ Search

Biomedical subjects

S Nee

Publications and source records attributed to S Nee.

At least 19 recordsLinked to original sources
PubMed1996

The maintenance of strain structure in populations of recombining infectious agents.

Using mathematical models that combine population genetic and epidemiological processes, we resolve the paradox that many important pathogens appear to persist as discrete strains despite the constant exchange of genetic material. We show that dominant polymorphic determinants (that is, those that elicit the most effective immune responses) will be organized into nonoverlapping combinations as a result of selection by the host immune system, thereby defining a set of discrete independently transmitted strains. By analysing 222 isolates of Neisseria meningitidis, we show that two highly polymorphic epitopes of the outer membrane protein PorA exist in nonoverlapping combinations as predicted by this general framework. The model indicates that dominant polymorphic determinants will be in linkage disequilibrium, despite frequent genetic exchange, even though they may be encoded by several unlinked genes. This suggests that the detection of nonrandom associations between epitope regions can be employed as a novel strategem for identifying dominant polymorphic antigens.

Genes, Dominant↗
PubMed1995

Inferring population history from molecular phylogenies.

Variable molecular sequences sampled from a population can be used to infer its dynamic history. Graphical methods are developed and applied to real data, illustrating ways of navigating through hypothesis space with two landmarks for reference: constant population size and exponentially growing population size.

Genetics, Population↗
PubMed1995

Revealing the history of infectious disease epidemics through phylogenetic trees.

Phylogenetic trees play an increasing role in molecular epidemiology, where they have been used to understand the forces that shape patterns of viral sequence diversity. Phylogenetic trees can also be used to trace the dynamics of viral transmission within populations. Case studies document the worldwide spread of Human Immunodeficiency Virus type 1 (HIV-1) and hepatitis C virus (HCV). Despite similarities between these viruses, especially in their transmission routes, they are shown to have very different epidemiological histories. A possible reason for the difference is that HCV has coexisted longer with human populations.

Communicable Diseases↗
PubMed1995

Macroevolutionary inferences from primate phylogeny.

We apply new statistical methods to a recent estimate of the phylogeny of all living primate species to test a range of models of cladogenesis. Null models in which probabilities of speciation and extinction do not differ among contemporaneous lineages are not consistent with the phylogeny. We present evidence that the net rate of cladogenesis (speciation rate minus extinction rate) increased in the lineage leading to the Cercopithecidae (Old World monkeys), and that there have been further increases in some lineages within that family. Such increases suggest the occurrence of clade selection, although we have not identified the selected trait or traits. There is no evidence that the net rate of cladogenesis is a function either of how many primate lineages are already present or of time. Intriguingly, three other clades--Strepsirhini, Platyrrhini and Hominoidea--appear to have had very similar rates of clade growth, in spite of their great biological differences.

Animals↗
PubMed1995

Sex allocation and population structure in malaria and related parasitic protozoa.

Here we demonstrate how sex allocation theory, one of the best verified areas of metazoan evolutionary biology, can be successfully applied to microparasitic organisms, by relating parasite prevalence and sex ratio in the Haemosporina. Members of this taxon, which includes Plasmodium, are parasitic protozoa with obligate sexual cycles in which dioecious haploid gametes drawn from the peripheral blood of a vertebrate host fuse within a dipteran vector. Consequently mating takes place within a highly subdivided population, a condition known to promote local mate competition and inbreeding and hence the evolution of female-biased sex ratios. We used an epidemiological framework to investigate mating patterns and sex ratio evolution within natural populations of these parasites. This phenotypic approach compliments more conventional biochemical approaches to the population genetics of parasitic protozoa. Data are presented which support a theoretical relation between transmission-stage sex ratio and prevalence across parasite populations. These results are consistent with a large inter-population variation in genetic structure and argue against sweeping generalizations about the clonality or otherwise of populations of these parasitic protozoa.

Animals↗
PubMed1994

The reconstructed evolutionary process.

Phylogenies reconstructed from contemporary taxa do not contain information about lineages that have gone extinct. We derive probability models for such phylogenies, allowing real data to be compared with specified null models of evolution, and lineage birth and death rates to be estimated.

Animals↗
PubMed1994

Model phylogenies to explain the real world.

Phylogenetic trees based on gene sequence data contain information about the evolutionary processes responsible for their genesis. Methods have now been developed which help to reveal those processes. The methods are based on simple models of evolutionary change but, when applied across individuals in a population, rather than across species in a higher-level taxon, they can reveal the past history of population change. Examples from salamanders and viruses are used to illustrate how the past history of changes in speciation rate and the origin of epidemics can be inferred in the absence of fossil material or historical documentation.

Animals↗
PubMed1992

Gametocyte sex ratios as indirect measures of outcrossing rates in malaria.

The frequency of recombination between unlike genotypes is central to understanding the generation of genetic diversity in natural populations of malaria. Here we suggest a way of investigating the problem which could complement conventional biochemical approaches to the population genetics of malaria. Sex allocation theory is one of the most successful areas of evolutionary biology. A well-supported prediction is that progressively less female-biased sex ratios are favoured with more outcrossing; equal numbers of males and females being evolutionarily stable in randomly mating outbred populations. We present a simple game theory model to support the idea that outcrossing rates in malaria will be correlated with the sex ratio of gametocytes in the peripheral blood of vertebrate hosts. Blood films from epidemiological surveys and culture-adapted isolates from Madang Province, Papua New Guinea, were used to estimate average gametocyte sex ratio of Plasmodium falciparum in the area. The geometric mean proportion of males in the population was 0.18 (95% confidence limits: 0.15-0.22). From our model, we estimate that, on average, 36% of zygotes are the result of outcrossing. This estimate assumes that most microgametes released following exflagellation are capable of fertilization. If, on average, fewer than about 70% of microgametes are capable of fertilization (as is the case in at least one other species of Plasmodium), the observed sex ratio would be consistent with between zero and 36% of zygotes being the result of outcrossing. These estimates suggest that there is usually a numerically dominant genotype in the gametocyte population in a blood meal, and that a considerable amount of selfing is occurring in P. falciparum populations in the Madang region, even though it is an area of intense year-round transmission.

Animals↗
PubMed1992

Population genetics and dynamics of Plasmodium falciparum: an ecological view.

Molecular characterization of the Plasmodium falciparum genome has led to identification of polymorphic loci and the mechanisms generating genetic diversity in this parasite. This information has resulted in the development of molecular methods to type parasite diversity in the field. Consequently, we are now in a position to describe the population genetics and dynamics of P. falciparum. The limited number of field studies that have been conducted to date have revealed an extraordinary degree of genetic diversity in natural parasite populations. Heterozygous recombination which occurs during meiosis appears to be one mechanism for generating genetic diversity. The rate at which such recombination occurs in natural parasite populations defines the genetic structure of the parasite population and can influence the ability of the parasite to respond to selection pressure. The high frequency of single genotype infections and the female-biased gametocyte sex ratios found in hyperendemic malaria areas suggest that self-fertilization occurs frequently. Population-wide surveys of allele frequencies in endemic areas have, however, shown no evidence of linkage disequilibrium and are consistent with a panmictic population structure. We argue that these studies have only sampled symptomatic infections, within which rare or recombinant genotypes may be disproportionately represented. They also take no account of the spatial structure of P. falciparum populations. Systematic investigations of the amount of heterozygosity in small areas as part of population-wide surveys are required to define the genetic structure of P. falciparum populations. Population dynamic studies which consider genetic heterogeneity of P. falciparum have shown fluctuations of different serotypes in space and time. The host immune response appears to play an important role in generating these dynamics. Integrated field and laboratory studies, which consider the interaction between population genetics and dynamics, will be necessary to describe the population biology of P. falciparum.

Animals↗
PubMed1989

Does Hamilton's rule describe the evolution of reciprocal altruism?

On intuitive grounds, many have felt that Hamilton's Rule, br greater than c, should describe the evolution of reciprocal altruism and "green beard" genes. However, difficulties have been encountered in applying the rule to situations in which the benefits an individual receives are a function of his own phenotype as well as that of his partner. These difficulties are resolved by recognising that there are two important coefficients of genetic relatedness: r1 is the coefficient already familiar to sociobiologists from the applications of Hamilton's Rule to kin selection; r2 is the coefficient of genetic relatedness between individuals who express the same phenotype. It is shown that the r in Hamilton's Rule is a weighted average of these two coefficients. The weights, along with r1 and r2, are intuitively meaningful. A remarkable fact is that r2 = 1, regardless of how genotype determines phenotype.

Altruism↗
PubMed1989

Antagonistic co-evolution and the evolution of genotypic randomization.

Antagonistic co-evolution, such as the pursuit and flight of host-parasite co-evolution, easily generates cyclical co-evolutionary dynamics. It is well known that a fluctuating, contrary environment may favour the evolution of recombination, but previous analyses have shown that the optimal rate of recombination declines as the period of the environmental fluctuations gets longer. It is here shown that the direction of selection for recombination (for higher or lower rates) may only be sensitive to fluctuation period if the fluctuations are generated by non-co-evolving features of the environment, such as changes in climate. In the simple model of this paper, co-evolutionary cycling provides an advantage for recombination that is independent of period length. This independence of period length necessitates a new framework for understanding the advantage of recombination in the context of co-evolution. In the model studied in this paper it is the phase difference of the host and parasite trajectories that is the relevant feature, and phase relationships are independent of the co-evolutionary cycle time. That is, the phase difference of the oscillations is independent of their frequency.

Biological Evolution↗