Malaria: Genetic and Evolutionary Aspects (Emerging Infectious Diseases of the 21st Century)

198 Pages·2010·1.17 MB·English

by  Krishna R. Dronamraju

Malaria: Genetic and Evolutionary
Aspects
Emerging Infectious Diseases of the 21st Century
Series Editor: I. W. Fong
Professor of Medicine, University of Toronto
Head of Infectious Diseases, St. Michael’s Hospital
Recent volumes in this series:
INFECTIONS AND THE CARDIOVASCULAR SYSTEM:New Perspectives
Edited by I. W. Fong
REEMERGENCE OF ESTABLISHED PATHOGENS IN THE 21STCENTURY
Edited by I. W. Fong and Karl Drlica
BIOTERRORISM AND INFECTIOUS AGENTS:A New Dilemma for the 21st Century
Edited by I. W. Fong and Kenneth Alibek
MALARIA: Genetic and Evolutionary Aspects
Edited by Krishna R. Dronamraju and Paolo Arese
A Continuation Order Plan is available for this series. A continuation order will bring delivery of
each new volume immediately upon publication. Volumes are billed only upon actual shipment. For
further information, please contact the publisher.
Malaria: Genetic and
Evolutionary Aspects
KRISHNA R. DRONAMRAJU
AND
PAOLO ARESE
Krishna R.Dronamraju Paolo Arese
President,Foundation for Department of Genetics,Biology
Genetic Research and Biochemistry
P.O.Box 27701-0 University of Torino Medical School
Houston,Texas 77227 Via Santena 5 bis,10126 Torino
USA Italy
[email protected] [email protected]
Library of Congress Control Number: 2005930721.
ISBN-10: 0-387-28294-7
ISBN-13: 9780387282947
©2006 Springer Science+Business Media, Inc.
All rights reserved. This work may not be translated or copied in whole or in part without the written
permission of the publisher (Springer Science+Business Media, Inc., 233 Spring Street, New York,
NY10013, USA), except for brief excerpts in connection with reviews or scholarly analysis, Use in
connection with any form of information storage and retrieval, electronic adaptation, computer
software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.
The use in this publicaiton of trade names, trademarks, service marks and similar terms, even if
they are not identified as such, is not to be taken as an expression of opinion as to whether or
notthey are subject to proprietary rights.
Printed in the United States of America.
9 8 7 6 5 4 3 2 1
springeronline.com
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
1. Introduction
Krishna R. Dronamraju
1. The Haldane Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Glucose-6-Phosphate Dehydrogenase Deficiency and Malarial Resistance . . . 5
3. Phagocytosis of Ring Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
4. Evolutionary Considerations: Malaria’s Eve Hypothesis . . . . . . . . . . . . . . . . . 6
5. Malaria Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2. J.B.S. Haldane (1892–1964)
Krishna R. Dronamraju
1. Population Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2. Beanbag Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3. Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
4. Human Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
5. Genetic Load Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
6. Immunogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
7. Sociobiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8. Daedalus and Eugenics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3. Removal of Early Parasite Forms from Circulation
as a Mechanism of Resistance Against Malaria
in Widespread Red Blood Cell Mutations
Paolo Arese, Kodjo Ayi, Aleksei Skorokhod and Franco Turrini
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2. Malaria is Responsible for High Frequency and Regional Distribution
of Major Protective RBC Mutations: Geographical Evidence . . . . . . . . . . . . . 27
3. Epidemiological Evidence: Degree of Protection Afforded
by RBC Mutations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.1. Hemoglobin AS (Sickle-Cell Trait) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2. Thalassemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3. Hemoglobin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
3.4. Hemoglobin E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
v
vi Contents
3.5. Glucose-6-Phosphate Dehydrogenase . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.6. Southeast Asian Ovalocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4. A Critical Assessment of the Current Mechanism of Protection
by Widespread RBC Mutations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.1. Sickle-Cell Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4.2. Beta-Thalassemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4.3. Alpha-Thalassemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
4.4. Glucose-6-Phosphate Dehydrogenase Deficiency . . . . . . . . . . . . . . . . . . . 38
5. Modifications in the RBC Membrane Elicited by the Developing
Parasite Induce Phagocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.1. Similarity of Ring Phagocytosis to Phagocytosis
of Normal Senescent or Oxidatively Stressed RBCs . . . . . . . . . . . . . . . . . 39
6. Enhanced Phagocytosis of Ring Forms as a Model of Protection
for Widespread RBC Mutations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
6.1. Membrane Binding of Hemichromes, Autologous IgG,
Complement C3c Fragment; Aggregated Band 3
and Phagocytosis in Nonparasitized and Ring-Parasitized
Normal and Mutant RBCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
6.2. Why are Rings Developing in Beta-Thalassemia, Sickle-Cell Trait,
HbH, and G6PD-deficient RBCs Phagocytosed More Intensely
than Rings Developing in Normal RBCs? . . . . . . . . . . . . . . . . . . . . . . . . 43
6.3. What is the Evidence that Ring-Parasitized Mutant RBCs are Also
Preferentially Removed In Vivo? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.4. Why is Preferential Removal of Ring-Forms Advantageous
to the Host? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
6.5. Why are Rings Developing in Alpha-Thalassemia Very Similar
to Controls? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
4. Clinical, Epidemiological, and Genetic Investigations
on Thalassemia and Malaria in Italy
Stefano Canali and Gilberto Corbellini
1. The Evolution of the Knowledge of Thalassemia Genetics:
The Italian Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2. Early Observations on the Association between Malaria and Thalassemia . . . . 58
3. Collaboration of Silvestroni and Bianco with Montalenti: At Work
on Haldane’s Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
4. Research of Carcassi etal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5. Studies on Microcythemia Genetics in Italy Funded
by the Rockefeller Foundation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
6. The Results of Siniscalco’s Genetic Studies on the Distribution
of Thalassemia, G-6-PD Deficit, and of Malaria . . . . . . . . . . . . . . . . . . . . . . . 74
7. The Malaria Hypothesis and the Consequences of Eradicating
the Plasmodia and of Thalassemia Prevention . . . . . . . . . . . . . . . . . . . . . . . . . 75
8. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Contents vii
5. Resistance to Antimalarial Drugs: Parasite and Host Genetic
Factors
Rajeev K. Mehlotra and Peter A. Zimmerman
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
2. Malaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
3. Antimalarial Chemotherapy and Chemoprophylaxis . . . . . . . . . . . . . . . . . . . . 83
3.1. Drugs Available for Treatment of Malaria . . . . . . . . . . . . . . . . . . . . . . . . 83
4. Antimalarial Drug Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
4.1. Current Status of Drug-Resistant Malaria . . . . . . . . . . . . . . . . . . . . . . . . 86
4.2. Parasite Genetic Polymorphism As a Basis
for Antimalarial Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
4.3. Genes Associated with Chloroquine Resistance in P. falciparum . . . . . . . 90
4.4. Mechanism of Resistance to Antifolate Combination Drugs
inP. falciparum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.5. Mechanism of Atovaquone Resistance in P. falciparum . . . . . . . . . . . . . . 94
4.6. Mechanisms of Drug Resistance in P. vivax . . . . . . . . . . . . . . . . . . . . . . . 95
5. Human Drug Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.1. Cytochrome P450 Enzyme Superfamily . . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.2. Uridine Diphosphate Glucuronosyltransferase Enzyme Superfamily . . . . 98
5.3. Antimalarial Drug Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
5.4. Antimalarial Drug Levels and Treatment Outcome . . . . . . . . . . . . . . . . . 104
6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
6. Evolutionary Origins of Human Malaria Parasites
Stephen M. Rich and Francisco J.Ayala
1. The Phylum Apicomplexa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
2. The Genus Plasmodium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
3. Transfers Between Human and Monkey Hosts . . . . . . . . . . . . . . . . . . . . . . . . 132
4. Population Structure of Plasmodium falciparum . . . . . . . . . . . . . . . . . . . . . . . 135
5. Malaria’s Eve Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
6. Malaria’s Eve Counterarguments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
7. Vector Genetics in Malaria Control
V.P. Sharma
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
2. The Anopheles culicifaciesComplex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
2.1. Paradox Resolved . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
3. Application in Malaria Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
3.1. Stratification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
3.2. Insecticide Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
3.3. Bioenvironmental Malaria Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
viii Contents
8. The Rate of Mutation of Human Genes 169
J.B.S. Haldane
9. Disease and Evolution 175
J.B.S. Haldane
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Preface
This book was originally conceived at a conference at the
University of Turin in Italy. The conference was organized to examine the
so-called “Malaria Hypothesis”, that is to say, the higher fitness of tha-
lassemia heterozygotes in a malarial environment, and to pay tribute to
the proponent of that hypothesis, J.B.S. Haldane. Contributors to this
book examine certain genetic and evolutionary aspects of malaria which
is a major killer of human populations, especially in Africa and Asia.
There were attempts to discredit Haldane’s contribution from two
directions: (a) it has been suggested that the “Malaria Hypothesis” was
known long before Haldane and that there was nothing original about his
idea (Lederberg 1999), and that (b) the hypothesis of heterozygote supe-
riority was first suggested by the Italian biologist Giuseppe Montalenti
who communicated his idea to Haldane (Allison 2004). Surely, both can-
not be right. In fact, the evidence presented in this book clearly indicates
that both are wrong.
Haldane’s malaria hypothesis has stimulated a great deal of research
on the genetic, evolutionary and epidemiological aspects of malaria dur-
ing the last 50 years. It has opened up a whole new chapter in the study
of infectious diseases. It deserves serious consideration.
For helpful discussions we thank Lucio Luzzatto, Alberto Piazza,
Guido Modiano and David Roberts.
Krishna R. Dronamraju
Paolo Arese
ix