<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ayala, F J</style></author><author><style face="normal" font="default" size="100%">Rich, S M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic variation and the recent worldwide expansion of Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Gene</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Gene</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Merozoite Surface Protein 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Phylogeny</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Repetitive Sequences, Nucleic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Ribosomal</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Homology, Nucleic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Species Specificity</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2000</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2000 Dec 30</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">261</style></volume><pages><style face="normal" font="default" size="100%">161-70</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Plasmodium falciparum, the agent of human malignant malaria, diverged from Plasmodium reichenowi, the chimpanzee parasite, about the time the human and chimpanzee lineages diverged from each other. The absence of synonymous nucleotide variation at ten loci indicates that the world populations of P. falciparum derive most recently from one single strain, or 'cenancestor,' which lived a few thousand years ago. Antigenic genes of P. falciparum (such as Csp, Msp-1, and Msp-2) exhibit numerous polymorphisms that have been estimated to be millions of years old. We have discovered in these antigenic genes short repetitive sequences that distort the alignment of alleles and account for the apparent old age of the polymorphisms. The processes of intragenic recombination that generate the repeats occur at rates about 10(-3) to 10(-2), several orders of magnitude greater than the typical mutational process of nucleotide substitutions. We conclude that the antigenic polymorphisms of P. falciparum are consistent with a recent expansion of the world populations of the parasite from a cenancestor that lived in tropical Africa a few thousand years ago.</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/11164047?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Ferreira, M U</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The origin of antigenic diversity in Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Parasitol Today</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Parasitol. Today (Regul. Ed.)</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Merozoite Surface Protein 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Homology</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2000</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2000 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">390-6</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Most studies of genetic variability of Plasmodium falciparum have focused on protein antigens and the genes that encode them. The consensus is that populations exhibit high levels of genetic polymorphism, most notably the genes encoding surface proteins of the merozoite (Msp1, Msp2) and the sporozoite (Csp). The age and derivation of this variation is a subject that warrants further careful consideration, as discussed here by Stephen Rich, Marcelo Ferreira and Francisco Ayala.</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/10951599?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Population structure and recent evolution of Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Proc Natl Acad Sci U S A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Proc. Natl. Acad. Sci. U.S.A.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Biological Evolution</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetics, Population</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2000</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2000 Jun 20</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">97</style></volume><pages><style face="normal" font="default" size="100%">6994-7001</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Plasmodium falciparum is the agent of malignant malaria, one of mankind's most severe maladies. The parasite exhibits antigenic polymorphisms that have been postulated to be ancient. We have proposed that the extant world populations of P. falciparum have derived from one single parasite, a cenancestor, within the last 5, 000-50,000 years. This inference derives from the virtual or complete absence of synonymous nucleotide polymorphisms at genes not involved in immune or drug responses. Seeking to conciliate this claim with extensive antigenic polymorphism, we first note that allele substitutions or polymorphisms can arise very rapidly, even in a single generation, in large populations subject to strong natural selection. Second, new alleles can arise not only by single-nucleotide mutations, but also by duplication/deletion of short simple-repeat DNA sequences, a process several orders of magnitude faster than single-nucleotide mutation. We analyze three antigenic genes known to be extremely polymorphic: Csp, Msp-1, and Msp-2. We identify regions consisting of tandem or proximally repetitive short DNA sequences, including some previously unnoticed. We conclude that the antigenic polymorphisms are consistent with the recent origin of the world populations of P. falciparum inferred from the analysis of nonantigenic genes.</style></abstract><issue><style face="normal" font="default" size="100%">13</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/10860962?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ayala, F J</style></author><author><style face="normal" font="default" size="100%">Escalante, A A</style></author><author><style face="normal" font="default" size="100%">Rich, S M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Evolution of Plasmodium and the recent origin of the world populations of Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Parassitologia</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Parassitologia</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Evolution, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Hominidae</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Merozoite Surface Protein 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Alignment</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">1999</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1999 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">41</style></volume><pages><style face="normal" font="default" size="100%">55-68</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">We have investigated the evolution of Plasmodium parasites by analyzing DNA sequences of several genes. We reach the following conclusions: (1) The four human parasites, P. falciparum, P. malariae, P. ovale, and P. vivax are very remotely related to each other, so that their evolutionary divergence predates the origin of the hominids; several of these parasites became associated with the human lineage by lateral transfer from other hosts. (2) P. falciparum diverged from P. reichenowi about 8 million years ago, consistently with the time of divergence of the human lineage from the apes; a parsimonious inference is that falciparum has been associated with humans since the origin of the hominids. (3) P. malariae is genetically indistinguishable from P. brasilianum, a parasite of New World monkeys; and, similarly. (4) P. vivax is genetically indistinguishable from the New World monkey parasite P. simium. We infer in each of these two cases a very recent lateral transfer between the human and monkey hosts, and explore alternative hypotheses about the direction of the transfer. We have also investigated the population structure of P. falciparum by analyzing 10 genes and conclude that the extant world populations of this parasite have evolved from a single strain within the last several thousand years. The extensive polymorphisms observed in the highly repetitive central region of the Csp gene, as well as the apparently very divergent two classes of alleles at the Msa-1 gene, are consistent with this conclusion.</style></abstract><issue><style face="normal" font="default" size="100%">1-3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/10697834?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Reply</style></title><secondary-title><style face="normal" font="default" size="100%">Parasitol Today</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Parasitol. Today (Regul. Ed.)</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">1999</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1999 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">39-40</style></pages><language><style face="normal" font="default" size="100%">Eng</style></language><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/10234178?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Licht, M C</style></author><author><style face="normal" font="default" size="100%">Hudson, R R</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Malaria's Eve: evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Proc Natl Acad Sci U S A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Proc. Natl. Acad. Sci. U.S.A.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Africa</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Asia</style></keyword><keyword><style  face="normal" font="default" size="100%">Climate</style></keyword><keyword><style  face="normal" font="default" size="100%">Demography</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Evolution, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Life Cycle Stages</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria, Falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Netherlands</style></keyword><keyword><style  face="normal" font="default" size="100%">Phylogeny</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">South America</style></keyword><keyword><style  face="normal" font="default" size="100%">Tetrahydrofolate Dehydrogenase</style></keyword><keyword><style  face="normal" font="default" size="100%">Time</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">1998</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1998 Apr 14</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">95</style></volume><pages><style face="normal" font="default" size="100%">4425-30</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">We have analyzed DNA sequences from world-wide geographic strains of Plasmodium falciparum and found a complete absence of synonymous DNA polymorphism at 10 gene loci. We hypothesize that all extant world populations of the parasite have recently derived (within several thousand years) from a single ancestral strain. The upper limit of the 95% confidence interval for the time when this most recent common ancestor lived is between 24,500 and 57,500 years ago (depending on different estimates of the nucleotide substitution rate); the actual time is likely to be much more recent. The recent origin of the P. falciparum populations could have resulted from either a demographic sweep (P. falciparum has only recently spread throughout the world from a small geographically confined population) or a selective sweep (one strain favored by natural selection has recently replaced all others). The selective sweep hypothesis requires that populations of P. falciparum be effectively clonal, despite the obligate sexual stage of the parasite life cycle. A demographic sweep that started several thousand years ago is consistent with worldwide climatic changes ensuing the last glaciation, increased anthropophilia of the mosquito vectors, and the spread of agriculture. P. falciparum may have rapidly spread from its African tropical origins to the tropical and subtropical regions of the world only within the last 6,000 years. The recent origin of the world-wide P. falciparum populations may account for its virulence, as the most malignant of human malarial parasites.</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/9539753?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The recent origin of allelic variation in antigenic determinants of Plasmodium falciparum.</style></title><secondary-title><style face="normal" font="default" size="100%">Genetics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Genetics</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Epitopes</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Merozoite Surface Protein 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Proteins</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">1998</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1998 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">150</style></volume><pages><style face="normal" font="default" size="100%">515-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/9841225?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Rosenthal, B M</style></author><author><style face="normal" font="default" size="100%">Telford, S R</style></author><author><style face="normal" font="default" size="100%">Spielman, A</style></author><author><style face="normal" font="default" size="100%">Hartl, D L</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Heterogeneity of the internal transcribed spacer (ITS-2) region within individual deer ticks.</style></title><secondary-title><style face="normal" font="default" size="100%">Insect Mol Biol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Insect Mol. Biol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Deer</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Ribosomal</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Heterogeneity</style></keyword><keyword><style  face="normal" font="default" size="100%">Ixodes</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">1997</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1997 May</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">123-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">To determine whether nuclear rDNA sequences provide a useful means for assessing the structure of populations of Ixodes ticks, we compared variability among copies of an internal transcribed spacer (ITS-2) sequence within individual ticks to the variability between ticks. At least 4% of the nucleotides comprising this sequence vary among the copies present within individual ticks. ITS-2 diversity in each of two ticks is nearly half as great as that reported between ticks from geographically disparate populations. Because individual ticks retain ancestral polymorphism, ITS-2 variation does not accurately reflect descent relationships among these ticks. Sequencing single copies of PCR-amplified ITS-2 therefore does not permit assessment of the phylogenetic relationships among the I. ricinus-like ticks in eastern North America. We recommend caution in future analyses, and emphasize the importance of procedures designed to ensure that the many paralogous copies of the rDNA cistron have been sufficiently homogenized by concerted evolutionary processes. Such precautionary measures will make certain that phylogenetic trees based on these gene sequences reflect the phyletic relatedness of the biological species.</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/9099576?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, S M</style></author><author><style face="normal" font="default" size="100%">Hudson, R R</style></author><author><style face="normal" font="default" size="100%">Ayala, F J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Plasmodium falciparum antigenic diversity: evidence of clonal population structure.</style></title><secondary-title><style face="normal" font="default" size="100%">Proc Natl Acad Sci U S A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Proc. Natl. Acad. Sci. U.S.A.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Phylogeny</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombination, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Homology, Amino Acid</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">1997</style></year><pub-dates><date><style  face="normal" font="default" size="100%">1997 Nov 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">94</style></volume><pages><style face="normal" font="default" size="100%">13040-5</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Plasmodium falciparum, the agent of malignant malaria, is one of mankind's most severe scourges. Efforts to develop preventive vaccines or remedial drugs are handicapped by the parasite's rapid evolution of drug resistance and protective antigens. We examine 25 DNA sequences of the gene coding for the highly polymorphic antigenic circumsporozoite protein. We observe total absence of silent nucleotide variation in the two nonrepeated regions of the gene. We propose that this absence reflects a recent origin (within several thousand years) of the world populations of P. falciparum from a single individual; the amino acid polymorphisms observed in these nonrepeat regions would result from strong natural selection. Analysis of these polymorphisms indicates that: (i) the incidence of recombination events does not increase with nucleotide distance; (ii) the strength of linkage disequilibrium between nucleotides is also independent of distance; and (iii) haplotypes in the two nonrepeat regions are correlated with one another, but not with the central repeat region they span. We propose two hypotheses: (i) variation in the highly polymorphic central repeat region arises by mitotic intragenic recombination, and (ii) the population structure of P. falciparum is clonal--a state of affairs that persists in spite of the necessary stage of physiological sexuality that the parasite must sustain in the mosquito vector to complete its life cycle.</style></abstract><issue><style face="normal" font="default" size="100%">24</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/9371796?dopt=Abstract</style></custom1></record></records></xml>