Micro-evolution and emergence of pathogens David J. Conway * , Cally Roper Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Received 2 August 2000; received in revised form 23 August 2000; accepted 1 September 2000 Abstract Changes in the epidemiology of infectious diseases are the direct result of ecological and evolutionary changes in hosts and parasites. Precisely what the causal processes are is rarely known in any particular case, and this hinders the design of appropriate control strategies. This is particularly so for emerging infections, as opportunity is rapidly lost to study the ecological parameters which might have affected initial emergence. However, molecular evolutionary studies of the pathogens can yield data which discriminate between possible causes. The current distribution of DNA sequence variation is important information which may reveal past and current changes in pathogen population structures, and can also identify adaptive changes in pathogen genes which have affected their evolution. Such studies have been quite intensively performed on particular viral and bacterial pathogens, and some of the successes of these are noted here. Approaches to understanding the recent evolution of eukaryotic pathogens are outlined, with particular reference to current problems of emerging zoonoses, and changes in virulence and drug resistance. q 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. Keywords: Population genetics; Evolution; Epidemiology; Emerging infections; Zoonosis; Drug resistance 1. Introduction Molecular evolutionary studies have contributed to understanding the epidemiological emergence of pathogens. This is best illustrated by studies on human immunode®- ciency viruses (HIV), at global [1±3], local [4,5], and within-host [6] levels. More broadly, emerging pathogens consist of a `mixed bag' of viruses, bacteria, fungi, proto- zoa, and metazoa, and the causes of their epidemiological emergence vary greatly. Research questions and methods which have been fruitful in one case may not be relevant in others, and the potential role of molecular evolutionary analyses requires some general consideration. Deciding what constitutes an `emerging disease' is some- what arbitrary, although a working de®nition given in the context of public health in the USA is a disease whose incidence in humans has increased within the last 2 decades or threatens to increase in the near future [7]. For discussion of biological principles, a more broad consideration is preferable, as all infectious diseases have `emerged' at one time or another. There are data to indicate that some endemic human diseases of historical antiquity, such as malaria and tuberculosis, have actually only emerged to be common in human populations in the relatively recent past [8±10]. Also, currently emerging diseases of diverse animal species are of importance in their own right, and may contribute to a general understanding [11,12]. Molecular genetic `typing' of pathogen isolates is now widely practised. The genetic characters are essentially DNA sequences, although it is sometimes adequately infor- mative and convenient to type de®ned sets of marker loci, in the form of single nucleotide polymorphisms (SNPs), simple sequence repeat microsatellite polymorphisms, or polymorphic gene products which are electrophoretically or serologically distinguished. The loci, and the purposes of their study, fall into two main classes: (i) gene loci with putatively functional alleles, which may determine pheno- types such as host-speci®city, virulence, or drug-resistance; (ii) loci with neutral alleles, which can give an indication of the way in which genetic variation has been affected by past and current population structure. At the outset of an investigation, assumptions need to be stated about whether alleles at particular loci are function- ally important and thus under selection, or whether they are neutral. If it is aimed to actually identify which loci have functional alleles under selection, particular design and analysis is required which may differ for studies on patho- gens which have undergone host-switching [13], or which are epidemic [14] or endemic [15]. Here we discuss some of International Journal for Parasitology 30 (2000) 1423±1430 0020-7519/00/$20.00 q 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. PII: S0020-7519(00)00126-0 www.parasitology-online.com * Corresponding author. Tel.: 144-20-7927-2331; fax: 144-20-7636- 8739. E-mail address: david.conway@lshtm.ac.uk (D.J. Conway).