Gardner M J, Tettelin H, Carucci D J, Cummings L M, Smith H O, Fraser C M, Venter J C, Hoffman S L
Institute of Genomic Research, Naval Medical Research Center, Rockville, MD, USA.
Parassitologia. 1999 Sep;41(1-3):69-75.
An international consortium has been formed to sequence the entire genome of the human malaria parasite Plasmodium falciparum. We sequenced chromosome 2 of clone 3D7 using a shotgun sequencing strategy. Chromosome 2 is 947 kb in length, has a base composition of 80.2% A + T, and contains 210 predicted genes. In comparison to the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, a greater proportion of genes containing introns, and nearly twice as many proteins containing predicted non-globular domains. A group of putative surface proteins was identified, rifins, which are encoded by a gene family comprising up to 7% of the protein-encoding gene in the genome. The rifins exhibit considerable sequence diversity and may play an important role in antigenic variation. Sixteen genes encoded on chromosome 2 showed signs of a plastid or mitochondrial origin, including several genes involved in fatty acid biosynthesis. Completion of the chromosome 2 sequence demonstrated that the A + T-rich genome of P. falciparum can be sequenced by the shotgun approach. Within 2-3 years, the sequence of almost all P. falciparum genes will have been determined, paving the way for genetic, biochemical, and immunological research aimed at developing new drugs and vaccines against malaria.
一个国际财团已组建起来,对人类疟原虫恶性疟原虫的全基因组进行测序。我们采用鸟枪法测序策略对克隆3D7的2号染色体进行了测序。2号染色体长度为947 kb,碱基组成为80.2%的A + T,包含210个预测基因。与酿酒酵母基因组相比,2号染色体的基因密度较低,含内含子的基因比例更高,且含有预测非球状结构域的蛋白质数量几乎是其两倍。一组假定的表面蛋白被鉴定出来,即环子孢子蛋白,它们由一个基因家族编码,该家族在基因组中占蛋白质编码基因的比例高达7%。环子孢子蛋白表现出相当大的序列多样性,可能在抗原变异中起重要作用。2号染色体上编码的16个基因显示出质体或线粒体起源的迹象,包括几个参与脂肪酸生物合成的基因。2号染色体序列的完成表明,恶性疟原虫富含A + T的基因组可以通过鸟枪法进行测序。在2至3年内,几乎所有恶性疟原虫基因的序列都将被确定,为旨在开发抗疟疾新药和疫苗的遗传、生化及免疫学研究铺平道路。