生物谷报道：2007年1月号的《自然—遗传学》期刊报道了研究疟疾寄生虫多样性的3篇独立论文。其中两篇关注的是恶性疟原虫(Plasmodium falciparum)，一篇关注的是亚种疟原虫（Plasmodium reichenowi）。
P. falciparum是最致命的疟原虫种类，能导致人类疟疾，P. reichenowi则可感染黑猩猩。这三篇论文的数据构建了一幅颇有价值的资源图谱，可以提高我们对疟疾抗药性的认识，并有助于鉴别出更好的潜在疫苗靶标。
Dyann Wirth和同事提供了一幅P. falciparum菌株多样性的基因组图谱，包括16个新菌株的全部基因组图谱和因地理位置不同而不同的菌株的基因组图谱，并对来自世界54个地方的隔离菌株的基因组进行了测序。在与之相伴随的一项研究中，Xin-zhuan Su、Philip Awadalla和同事专门测量了负责编码隔离菌株4 P. falciparum内蛋白质的基因组片段。他们测量了近3500个基因，约占基因组的19%，获得高分辨率的基因组变化图谱，报告了可作为疫苗靶标的7个候选目标。在第三篇论文中， Manolis Dermitzakis、Matthew Berriman和同事提供了世界上第一个P. reichenowi菌株的基因组图谱，以及两个P. falciparum菌株的序列，并检测了两个菌株间的进化差异。其中一个P. falciparum菌株是在临床中从来自加纳的一位感染者体内分离出的未培育菌株，也许它能比实验室培养的其他菌株提供更好的模式。
Figure 1. Geographic distribution of parasites and SNPs.
(a) Sequence data derived from 18 parasites were used for SNP identification, including HB3 (red) and Dd2 (green), for which we obtained the full genome sequence; 12 additional parasites (blue) for which we obtained low-coverage sequence and four additional parasites (gray) that were used with the 12 low-coverage parasites for PCR product sequencing of 20 core regions across the genome (Supplementary Table 2). (b) SNPs identified from the parasites shown in a provide four data sources, including full-genome sequencing of HB3 (red) and Dd2 (green), low-coverage sequencing of 12 additional parasites (blue) and sequencing of 18 kb across 20 core regions (PCR) in 16 parasites (gray). The total number of SNPs identified for each of the four sources (HB3, Dd2, low coverage and PCR) is indicated by source, totaling 46,937 overall. The inner pie chart (light shading) indicates the number of SNPs by source that were found in more than one source ('shared'), identifying a total of 12,188 individual SNP positions that were identified in at least two sources. The outer pie chart (dark shading) indicates the number of SNPs identified only in a single source ('private').
原文出处：
Nature Genetics January 2007, Volume 39 No 1
A genome-wide map of diversity in Plasmodium falciparum pp113 - 119
Sarah K Volkman, Pardis C Sabeti, David DeCaprio, Daniel E Neafsey, Stephen F Schaffner, Danny A Milner Jr, Johanna P Daily, Ousmane Sarr, Daouda Ndiaye, Omar Ndir, Soulyemane Mboup, Manoj T Duraisingh, Amanda Lukens, Alan Derr, Nicole Stange-Thomann, Skye Waggoner, Robert Onofrio, Liuda Ziaugra, Evan Mauceli, Sante Gnerre, David B Jaffe, Joanne Zainoun, Roger C Wiegand, Bruce W Birren, Daniel L Hartl, James E Galagan, Eric S Lander & Dyann F Wirth
Published online: 10 December 2006 | doi:10.1038/ng1930
Abstract | Full text | PDF (362K) | Supplementary Information
See also: News and Views by Carlton
Genome variation and evolution of the malaria parasite Plasmodium falciparum pp120 - 125
Daniel C Jeffares, Arnab Pain, Andrew Berry, Anthony V Cox, James Stalker, Catherine E Ingle, Alan Thomas, Michael A Quail, Kyle Siebenthall, Anne-Catrin Uhlemann, Sue Kyes, Sanjeev Krishna, Chris Newbold, Emmanouil T Dermitzakis & Matthew Berriman
Published online: 10 December 2006 | doi:10.1038/ng1931
Abstract | Full text | PDF (386K) | Supplementary Information
See also: News and Views by Carlton
Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome pp126 - 130
Jianbing Mu, Philip Awadalla, Junhui Duan, Kate M McGee, Jon Keebler, Karl Seydel, Gilean A T McVean & Xin-zhuan Su
Published online: 10 December 2006 | doi:10.1038/ng1924
Abstract | Full text | PDF (220K) | Supplementary Information
See also: News and Views by Carlton
作者简介：
Philip Awadalla
Awadalla Homepage
Assistant Professor of Genetics
PhD, University of Edinburgh, UK
Postdoctoral, University of British Columbia, Canada
Postdoctoral, University of California, Davis, USA
Evolutionary Genomics
Primary research interests include 1) inferring the genomic targets and of adaptations in humans and human pathogens (with emphasis on Malaria), 2) the evolution of mutation and recombination across eukaryotic genomes, and 3) the evolution of mating systems. We develop and use model-based evolutionary genetic approaches combined with genomic and expression variability data to infer evolutionary histories. A coherent framework is necessary to analyse data of this magnitude, and are critical for identifying genomic regions of evolutionary or functional importance in human genomes for example, or for determining how parasites evolve and adapt to their hosts.
The Evolution of Primate and Pathogen Genomes and their Interactions
Malaria kills more people than all inherited human disorders combined. Critical to controlling this disease through drugs or vaccines is identifying the mutations associated with host or mosquito immune evasion at agenome-wide or global scale. Past and current efforts use models and data to examine how genes evolve in human and pathogen systems. Our research with humans and pathogens such as malaria develops upon established methods for non-random mating populations that are applicable to estimating the mode and strength of adaptation, mutation, recombination and protein interactions between primates and other pathogens. Currently, we are investigating three main areas: 1) can population data and structure help reveal the genomic targets critical for host or parasite survival, 2) how clonal are pathogens and 3) can genome-wide variation within and among populations, combined with functional analyses, identify co-evolving genomic regions in both humans and the parasite. Identifying such targets are critical for drug or vaccine development. We are also developing approaches to examine how selective constraints and substitution rates vary across Plasmodium and primate lineages and genomes using very large amounts of genomic information.
The Evolution of Sex, Recombination and Gene Conversion
Determining the amount of recombination in genealogical histories is important to both evolutionary biology and medical population genetics. Current and future research includes developing approaches to measure the scale of recombination variation within genomes and across species in a coalescent framework, and apply them to large-scale population and genomic data for humans and various pathogens. This provides us with a genome-wide perspective of how recombination evolves across genomes.
Inferences of Demography and Selection from Whole Genome Variation in Primates and Pathogens
Most methods that infer departures from neutrality were developed either for single coding regions, or multiple non-coding molecular markers scattered throughout the genome. Given the extensive genomic variation now available, the new challenge is to either adapt these approaches to the new data, or develop new tools. We are currently attempting to do both, with emphasis on applying these methods to both human and malaria whole genome data. Much of the malaria data is collected by us in collaboration with colleagues at the NIH (Xinzhuan Su). In collaboration with colleagues we are developing genome wide maps of variation of P. falciparum, the main agent of malaria.
also see:
http://www.ncsu.edu/news/press_releases/06_08/129.htm
Dyann Wirth
Professor of Immunology and Infectious Diseases II, Director
Homepage
Research affiliations
Biological Sciences, Division of (FAS) Immunology and Infectious Diseases, Dept. of (HSPH) Malaria Initiative, Harvard (HSPH)
Recent articles
HSPH, Broad map malaria genetic diversity (Harvard University Gazette, 12/10/2006) Harvard researchers complete genomic sequence of deadly malaria parasite (School of Public Health, 10/2/2002) Deadliest form of malaria is younger than previously believed (School of Public Health, 7/19/2001)
Matthew Berriman
dr matt berriman
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