生物谷報道：2007年1月號的《自然—遺傳學(xué)》期刊報道了研究瘧疾寄生蟲多樣性的3篇獨(dú)立論文。其中兩篇關(guān)注的是惡性瘧原蟲(Plasmodium falciparum),，一篇關(guān)注的是亞種瘧原蟲（Plasmodium reichenowi）。
P. falciparum是最致命的瘧原蟲種類,，能導(dǎo)致人類瘧疾,，P. reichenowi則可感染黑猩猩。這三篇論文的數(shù)據(jù)構(gòu)建了一幅頗有價值的資源圖譜,，可以提高我們對瘧疾抗藥性的認(rèn)識,，并有助于鑒別出更好的潛在疫苗靶標(biāo)。
Dyann Wirth和同事提供了一幅P. falciparum菌株多樣性的基因組圖譜,，包括16個新菌株的全部基因組圖譜和因地理位置不同而不同的菌株的基因組圖譜,，并對來自世界54個地方的隔離菌株的基因組進(jìn)行了測序。在與之相伴隨的一項(xiàng)研究中,，Xin-zhuan Su,、Philip Awadalla和同事專門測量了負(fù)責(zé)編碼隔離菌株4 P. falciparum內(nèi)蛋白質(zhì)的基因組片段。他們測量了近3500個基因,，約占基因組的19%,，獲得高分辨率的基因組變化圖譜，報告了可作為疫苗靶標(biāo)的7個候選目標(biāo),。在第三篇論文中,， Manolis Dermitzakis、Matthew Berriman和同事提供了世界上第一個P. reichenowi菌株的基因組圖譜,，以及兩個P. falciparum菌株的序列,，并檢測了兩個菌株間的進(jìn)化差異。其中一個P. falciparum菌株是在臨床中從來自加納的一位感染者體內(nèi)分離出的未培育菌株,，也許它能比實(shí)驗(yàn)室培養(yǎng)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').
原文出處：
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
作者簡介：
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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