Infectious Disease and Host-Pathogen Evolution / Edition 1

by Krishna R. Dronamraju

Overview

From the historical beginnings of Haldane's original hypothesis to current research, this book evaluates infectious diseases from an evolutionary perspective. It surveys the latest information related to major infections, such as malaria, influenza and leishmaniasis.

Product Details

ISBN-13:	9780521820660
Publisher:	Cambridge University Press
Publication date:	04/05/2004
Edition description:	New Edition
Pages:	396
Product dimensions:	6.30(w) x 9.21(h) x 0.94(d)

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Cambridge University Press
0521820669 - Infectious Disease and Host-Pathogen Evolution - Edited by Krishna R. Dronamraju
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Introduction

Krishna R. Dronamraju

The subject of infectious disease has never before been so intricately linked to our daily lives as it is today. Recent political and social events have underscored the importance of understanding the forces that have shaped, and continue to shape, the evolution of infectious diseases and their underlying genetic basis. The following chapters discuss infectious disease from an evolutionary perspective within the context of the occurrence of genetic polymorphisms in human populations. It was my mentor, J. B. S. Haldane (1949a, b), who first drew attention to the significant role infectious diseases have played in shaping our own evolution.

Haldane's idea was the culmination of long years of investigation into the fundamental nature of evolutionary forces that have shaped the biology of all species on this planet (Haldane 1924, 1932). He was one of the great trio of founding fathers of population genetics, the two others being R. A. Fisher and S. Wright. Haldane and Fisher were also pioneers in human genetics. Haldane contributed quite profoundly to pedigree analysis and gene mapping, as well as to the estimation of mutation rates, selection effects and other branches of human population genetics, and the impact of genetic knowledge on our ethical outlook (Dronamraju 1990, 1995).

In his often-quoted paper, entitled "Disease and Evolution," Haldane (1949b) wrote: ". . . the struggle against disease, and particularly infectious disease, has been a very important evolutionary agent, and that some of its results have been rather unlike those of the struggle against natural forces, hunger, and predators, or with members of the same species." Haldane further pointed out that a disease may be an advantage in certain instances, suggesting that "Europeans have used their genetic resistance to such viruses as that of measles as a weapon against primitive peoples as effective as fire-arms." He suggested further that, in certain circumstances, parasitism will be a factor promoting polymorphism and may even tend to encourage speciation. Haldane (1949b) has been often credited with the idea that the very high frequency of thalassemia that is found in the Mediterranean region might reflect heterozygote advantage against malaria. However, Haldane's (1949b) reference to the greater resistance of thalassemia heterozygotes to malaria does not appear in the text of that paper but in the discussion footnotes where the Italian biologist Giuseppe Montalenti acknowledges (in Italian) Haldane's idea as a personal communication. Consequently, some English-language readers appear to be confused about the precise nature of Haldane's contribution to this important subject.

In his contribution, Weatherall (p. 19) has drawn attention to a slightly earlier publication of Haldane's (1949a), in which Haldane stated his idea clearly and explicitly. Haldane (1949a) wrote: ". . . the possibility that the heterozygote is fitter than the normal must be seriously considered . . . The corpuscles of the anaemic heterozygotes are smaller than normal and more resistant to hypotonic solutions, . . . more resistant to attacks by the sporozoa which cause malaria, a disease prevalent in Italy, Sicily and Greece, where the gene is frequent." Haldane's comments were made while discussing Neel and Valentine's (1947) estimate for the mutation rate for thalassemia major (Cooley's anemia). Haldane (1949a) wrote: "Neel and Valentine believe that the heterozygote is less fit than normal, and think that the mutation rate is above 4 × 10^-4 rather than below it. I believe that the possibility that the heterozygote is fitter than the normal must be seriously considered. Such increased fitness is found in the case of several lethal and sublethal genes in Drosophila and Zea." Haldane (1949a) noted that if the heterozygote had an increased fitness of only 2%, this would account for the incidence without invoking any mutation at all. Earlier, in his classic, The Causes of Evolution, Haldane (1932) wrote that a study of the causes of death in man, animals, and plants clearly indicates that one of the principal agents of survival during the course of evolution is immunity to disease.

In a review of Haldane's paper of 1949b,¹ Lederberg (1999) cited previous work on host resistance genes against rust fungi in wheat. However, no previous author before Haldane (1949a, b) had suggested the evolutionary role of resistance against infectious disease with special reference to heterozygosity in human populations. By drawing attention to Haldane's (1949a) earlier paper, where Haldane made a direct reference to the greater fitness of thalassemia heterozygotes, Weatherall (2004) has cleared up the matter of priority on this subject. Crow has briefly reviewed Haldane's ideas with special reference to disease and evolution in his introductory essay.

INFECTIOUS DISEASES

Much of the general information about infectious diseases can be easily accessed from such sources as the World Health Organization (WHO) and Centers for Disease Control (CDC) websites on the internet. Infectious diseases are responsible for almost half of the mortality in developing countries. AIDS, malaria, and tuberculosis cause much of the mortality. Population movements and lack of even the most basic measures of public hygiene complicate the picture. The emergence of drug resistance and the absence of effective vaccines are worsening the situation. Current scientific and medical tools are far from satisfactory, partly because the methodologies employed are cumbersome and expensive and are not designed to yield immediate results. Meanwhile, pathogens are evolving ever more rapidly. Research has been compartmentalized to such an extent that it has hampered an integrated approach to the study of the coevolution of host-pathogen vectors (Tibayrenc 2001, 2004). Research described in the following pages emphasizes the need to study host-pathogen coevolution.

MALARIA

Several papers are devoted to malaria. Almost three million malaria-related deaths are estimated to occur each year, largely in sub-Saharan Africa. More than 40% of the world's population lives in countries where the disease is endemic. In view of the enormity of this problem, it is encouraging that the genome sequences of the major mosquito vector Anopheles gambiae and of the parasite Plasmodium falciparum were recently published. The availability of these sequence data and that of the human host will accelerate further research aimed at solving a number of puzzles, such as the identification of potential vaccine antigens and the manipulation of genomes to block transmission of disease. Future progress will depend on close collaboration among many participants worldwide, especially those in malaria-endemic countries.

Haldane's idea opened up a whole new field of evolutionary epidemiology. This subject is reviewed by Weatherall. The first evidence in support of Haldane's hypothesis came in the mid-1960's, when it was found that heterozygotes for the sickle cell gene might be protected against Plasmodium falciparum malaria. More recently it has been found that the heterozygous state for Hb S offers approximately 80% protection against cerebral malaria or the profound anemia of malaria.

Genetic diversity of the malarial parasite Plasmodium falciparum has rightly received the most attention. However, the development of antimalarial vaccines has been hampered by the extensive polymorphism observed in Plasmodium's proteins. Among the several studies that have taken place, Escalante et al. (1998) studied the genetic polymorphism at ten Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. They concluded that at five of the loci there is definite evidence for positive selection and that even moderate or low host immune activity generates sufficient selective pressure to be detectable in the parasite's polymorphism. The study of genetic diversity of P. falciparum is hampered by certain limitations. The number of gene loci studied remains small. Malaria research has focused upon immunologically relevant protein parts. The polymorphism of the gene cannot be assessed completely. In the present volume, Escalante and Lal review the current status of molecular evolutionary and population genetic research of malarial parasites, emphasizing the need for longitudinal studies that link population-based information with clinical end points. Another aspect, molecular variation at the G6PD locus in relation to resistance against malarial infection, is reviewed by Tishkoff and Verelli in this volume.

The antiquity of these polymorphisms is of much interest. Rich and Ayala (2000) have proposed that P. falciparum is derived from a single parasite during the past 5,000 to 50,000 years. In the following pages, Rich and Ayala have suggested that the extant world populations of P. falciparum have evolved from a single strain within the past several thousand years. Their estimate is in sharp contrast with that of Hughes and colleagues (Hughes 1993; Hughes and Hughes 1995; Hughes and Verra 2001), who proposed a model that requires that variants of genes encoding P. falciparum surface proteins may be older than the species itself. Their original estimates of the ages of the most divergent alleles (of Msp-1 and Csp) are 35 million and 2.1 million years, respectively. However, on the basis of an analysis of introns, Volkman et al. (2001) have estimated the age of the most recent common ancestor of all extant P. falciparum to be between 3,200 and 7,700 years. Population genetic studies of P. falciparum have produced conflicting results. Some have suggested that today's population includes multiple ancient lineages predating human speciation, whereas others suggest it includes one or a small number of these ancient lineages.

Zimmerman investigated the relationship between Duffy blood group and resistance to Plasmodium vivax. Two central issues are: Does P. vivax impose a selective burden on human survival? Did the heterozygous Duffy-negative condition increase fitness sufficiently to explain the dramatic fixation of this trait in human populations living in malaria-endemic Africa?

Evolutionary considerations of other parasites include the dynamics of Daphnia and their microparasites by Little and Ebert, susceptibility to visceral leishmaniasis and to schistosomiasis by Dessein et al., and the evolution of influenza viruses by Bush and Cox.

GENETIC AND EVOLUTIONARY CONSIDERATIONS

In their paper "Infection and the Diversity of Regulatory DNA," Cowell et al. pose a number of intriguing questions, such as "Can regulatory DNA be identified from its sequence properties?," and "Can we detect a pattern in the appearence of nucleotide substitutions in the promoter region, or do they occur at random?," etc. Whether it is regulatory DNA discussed by these authors, or linkage disequilibrium discussed by Morton, or Cavalli-Sforza on cultural evolution, these authors are concerned with aspects of infectious disease that have so far not received adequate attention. A different perspective is presented by Cochran and Cochran who argue in favor of the infectious etiology of diabetes.

VIRULENCE

Read et al. discuss the evolution of pathogen virulence in response to public health intervention, utilizing a model with the following assumptions: there is genetic variation in parasite virulence; vaccination is imperfect; there is a positive genetic correlation between virulence and transmission; and the cost of virulence is host death.

The evolution of virulence can be affected in rapidly evolving pathogens when only a few individual pathogens are transmitted from one infected host to another in the process of initiating a new infection. Bergstrom et al. (1999) observed that such bottlenecks are likely to drive down the virulence of a pathogen because of stochastic loss of the most virulent pathogens, through a process analogous to Muller's ratchet. These authors argued that the patterns of accumulation of deleterious mutation may explain differing levels of virulence in vertically and horizontally transmitted diseases. Furthermore, it has been suggested that virulence should be low in vertically transmitted diseases, because high virulence reduces the number of offspring produced, resulting in a reduction of the available pool of new infections (Ewald 1994). On the other hand, virulence can be higher in horizontally transmitted pathogens, because their survival is not solely dependent on the host's descendants. There is reason to believe that under horizontal transfer more virulent strains are able to transfer their abundance to other hosts and that natural selection will maintain high virulence in horizontally transmitted pathogens.

FURTHER RESEARCH

These are rapidly changing fields. Advances within each of these disciplines may soon render the accounts presented here obsolete. Meanwhile, I hope these accounts will have served a purpose as stepping stones in aiding that eventuality. Some key areas for further research on the evolutionary aspects of the host-pathogen relationship are outlined in the following summary.

(1)	Causes and sources of infectious diseases:
	(a) genetic variation and structure of pathogen populations and the genetic relationships between pathogenic members of closely related taxa;
	(b) population analyses of the contributions and sources of transfer of genes and accessory elements coding for virulence determinants, host range and specificity, and drug resistance; and
	(c) genetic factors (pathogen, host, or vector) responsible for geographic and temporal variations in disease frequency and severity.
(2)	Biology of pathogens:
	(a) genetic and evolutionary history of host-pathogen range;
	(b) model systems exploring the molecular biology of host barriers encountered by pathogens; and
	(c) exploration of molecular and pathogen models involving the extension of the host range of pathogens.
(3)	Interactions between hosts and pathogens:
	(a) contribution of population dynamic and evolutionary processes to the pathogenesis and virulence of infecting organisms; and
	(b) exploration of model systems to investigate the relationship between the evolution of pathogenic organisms and factors affecting host susceptibility.
(4)	Consequences of intervention:
	(a) in the host, reversion to virulence of live vaccines and evolution of resistance following vaccination;
	(b) exploration of model systems to predict the genetic and evolutionary consequences of vaccination, antimicrobial drug therapy, and other intervention strategies on host, pathogen, and vector populations;
	(c) mechanisms and consequences of antibiotic action;
	(d) investigation of new resistance mechanisms and evolutionary strategies to aid drug development; and
	(e) exploration of genetic, physiological, and environmental variables that are involved in generating and maintaining variation in pathogen, host, and vector populations.

ACKNOWLEDGMENTS

The idea for this book was first suggested by some colleagues who took part in a conference at the U.K. Genome Centre Campus at Hinxton. I was responsible for organizing that conference with the kind support of the Wellcome Trust. Several individuals provided advice and support, although only some of those who took part in the conference contributed to this book. Others who were not able to attend the conference also contributed some chapters. In particular, I would like to thank David Weatherall, Adrian Hill, Debbie Carly, and Pat Goodwin for help with the program. I am grateful to Katrina Halliday and Michael Shelley at Cambridge University Press for editorial help with the publication.

REFERENCES

Bergstrom, C. T., McElhany, P., and Real, L. A. (1999). Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens. Proc. Natl. Acad. Sci. USA, 96, 5095-100.

Dronamraju, K. R., Ed. (1990). Selected Genetic Papers of J. B. S. Haldane. Garland Publishing Co., New York.

Dronamraju, K. R., Ed. (1995). Haldane's Daedalus Revisited. Oxford University Press, Oxford.

Escalante, A. A., Freeland, D. E., Collins, W. E., and Lal, A. A. (1998). The evolution of primate malaria parasites based on the gene encoding cytochrome b from the linear mitochondrial genome. Proc. Natl. Acad. Sci. USA, 95, 8124-9.

Ewald, P. W. (1994). Evolution of Infectious Diseases. Oxford University Press, Oxford.

Haldane, J. B. S. (1924). A mathematical theory of natural and artificial selection. Part I. Trans. Camb. Phil. Soc., 23, 19-41.

Haldane, J. B. S. (1932). The Causes of Evolution. Longmans, Green, London.

Haldane, J. B. S. (1949a). The rate of mutation of human genes. In Proceedings of the Eighth International Congress of Genetics, Hereditas, 35, 267-73.

Haldane, J. B. S. (1949b). Disease and evolution. La Ricerca Scientifica, 19, 2-11.

Hughes, A. L. (1993). Coevolution of immunogenic proteins of Plasmodium falciparum and the host's immune system. In Mechanisms of Molecular Evolution (N. Takahata and A. G. Clark, Eds.), pp. 109-27. Sinauer Assoc., Sunderland, MA.

Hughes, A. L., and Hughes, M. K. (1995). Natural selection in Plasmodium surface proteins. Mol. Biochem. Parasitol., 71, 99-113.

Hughes, A. L., and Verra, F. (2001). Very large long-term effective population size in the virulent human malaria parasite Plasmodium falciparum. Proc. R. Soc. Lond., B, 268, 1855-60.

Lederberg, J. (1999). J. B. S. Haldane (1949) on infectious disease and evolution. Genetics, 153, 1-6.

Neel, J. V., and Valentine, W. N. (1947). Further studies on the genetics of thalassaemia. Genetics, 32, 38-63.

Rich, S. M., and Ayala, F. J. (2000). Population structure and recent evolution of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA, 97, 6994-7001.

Siddiqui, M. R., and colleagues (2001). A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat. Genet., 27, 439-41.

Tibayrenc, M. (2001). The golden age of genetics and the dark age of infectious diseases. Infect., Genet., Evol., 1 (1), 1-2.

Tibayrenc, M. (2004). The impact of human genetic diversity in the transmission and severity of infectious diseases. In Infectious Disease and Host-Pathogen Evolution (K. R. Dronamraju, Ed.), p. 315, 2004. Cambridge University Press, Cambridge, UK (this volume).

Volkman, S. K., Barry, A. E., Lyons, E. J., Nielsen, K. M., Thomas, S. M., Choi, M., Thakore, S. S., Day, K. P., Wirth, D. F., and Hartl, D. L. (2001). Recent origin of Plasmodium falciparum from a single progenitor. Science, 293, 482-4.

Weatherall, D. J. (2004). J. B. S. Haldane and the malaria hypothesis. In Infectious Disease and Host-Pathogen Evolution (K. R. Dronamraju, Ed.), p. 18, 2004. Cambridge University Press, Cambridge, UK (this volume).

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PART ONE

J. B. S. HALDANE

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J. B. S. Haldane (1892-1964) arriving in India, 1957 (photo courtesy of Indian Statistical Institute).

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© Cambridge University Press

Table of Contents

Part I. J. B. S. Haldane: 1. Haldane's ideas in biology with special reference to disease and evolution James F. Crow; 2. JBS Haldane and the malaria hypothesis D. J. Weatherall; Part II. malarial parasites: 3. Evolutionary genetics of Plasmodium Falciparum, the agent of malignant malaria Stephen M. Rich and Francisco J. Ayala; 4. Evolutionary biology of malaria parasites Ananias A. Escalante and Altaf A. Lal; 5. G6PD deficiency and malarial resistance in humans: insights from evolutionary genetic analyses Sara A. Tishkoff and Brian C. Verrelli; 6. The enigma of vivax malaria and erythrocyte duffy-negativity Peter A. Zimmerman; Part III. Other Parasites: 7. Influenza evolution Robin M. Bush and Nancy J. Cox; 8. Free-living to free-wheeling: the evolution of Vibrio cholerae from innocence to infamy Rita R. Colwell, Shah M. Faruque and G. Balakrish Nair; 9. Evolutionary dynamics of Daphnia and their microparasites Tom Little and Dieter Ebert; 10. Human susceptibility to visceral Leishmaniasis (Leishmania donovani) and to Schistosomiasis (Schistosoma mansoni) is controlled by major genetic loci A. Dessein, B. Bucheton, L. Argiro, N. M. A. Elwali, V. Rodrigues, C. Chevillard, S. Marquet, Helia Dessein, S. H. El-Safi and L. Abel; Part IV. Genetic and Evolutionary Considerations: 11. The evolution of pathogen virulence in response to animal and public health interventions Andrew F. Read, Sylvain Gandon, Sean Nee and Margaret J. Mackinnon; 12. Infection and the diversity of regulatory DNA Lindsay G. Cowell, N. Avrion Mitchison and Brigitte Muller; 13. Genetic epidemiology of infectious diseases: the first half century Newton E. Morton; 14. The impact of human genetic diversity in the transmission and severity of infectious diseases Michel Tibayrenc; 15. Evolution and the etiology of diabetes mellitus Kyle D. Cochran and Gregory M. Cochran; 16. The future of human evolution Luca Cavalli-Sforza.

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Review of the hardback: '… some fascinating reading.' Society for General Microbiology

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