ARTICLES Schistosomiasis is an important public health problem today 1 . Three main schistosome species, S. japonicum, S. mansoni and S. haemato- bium, infect humans. S. haematobium occurs in Africa and the eastern Mediterranean and causes urinary schistosomiasis. S. mansoni, endemic to Africa, the Caribbean and South America, results in intestinal schisto- somiasis. S. japonicum, the Asian schistosome, causes intestinal schisto- somiasis in China and some other oriental countries. For the most part, molecular phylogenies of the schistosomes agree with observations based on morphological or life-history characteristics 2,3 . Unlike most other platyhelminths, however, schistosomes are dioecious, and unlike Caenorhabditis elegans, schistosomes are sexually dimorphic as adults 4,5 . Schistosomes have a complex life cycle. Free-swimming larvae called cercariae directly penetrate human skin to accomplish infection. The cercariae shed their tails and transform their trilaminate tegument into the heptalaminate form adapted to the mammalian environment. After several days, developing male and female worms depart the lungs and move into the hepatic portal system to mature, pair up and migrate upstream to the mesenteric venules of the intestines. Eggs produced by female worms traverse the intestinal or bladder wall and are discharged with the feces or urine. But many eggs are retained in the liver and other organs and become the key contributor to the morbidity and mortality of schistosomiasis 6 . The relationship between schistosomes and their hosts is highly adapted and seems to involve parasite exploitation of host endocrine and immune signals 7,8 . Certain aspects of parasite biology, drug resis- tance and immune evasion strategies that enable avoidance of the host immune system have long perplexed clinicians and investigators intent on controlling this parasitic disease. Greater knowledge of the schisto- some genome has become increasingly important for understanding these complex issues. We recently began a gene discovery program for S. japonicum and report here transcriptome information obtained from ∼50,000 randomly selected cDNA clones from female, male and mixed-sex groups of adult worms and from S. japonicum eggs. The 13,131 gene clusters represented by these ESTs probably comprise most of the protein-coding genes of schistosomes, given that these parasites have ∼15,000 genes 9 . The availability of these new sequences should lead to a more profound understanding of the schistosome genome and the molecular pathogenesis of schistosomiasis and to new intervention strategies. RESULTS Comparative genomics analysis of S. japonicum cDNA data As a key initial step towards sequencing the complete genome sequence of S. japonicum, we generated ESTs from adult females and males and from eggs by an approach similar to that used with Drosophila 10 . We sequenced the 5′ ends of 48,251 clones selected at random from cDNA libraries of eggs and of male, female and mixed- sex adult worms. We removed repetitive, mitochondrial and ambigu- ous sequences and analyzed 43,707 5′ EST sequences more fully (3,871, 11,683, 13,285 and 14,868 from mixed-sex adults, males, 1 Chinese National Human Genome Center at Shanghai, 351 Guo shou-Jing Road, Shanghai 201203, China. 2 Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 207 Rui-Jin Road II, Shanghai 200025, China. 3 Department of Parasitology, Shanghai Second Medical University, 280 South Chong-Qing Road, Shanghai 200025, China. 4 State Key Laboratory of Medical Genomics, Rui Jin Hospital affiliated to Shanghai Second Medical University, 197 Rui-Jin Road II, Shanghai 200025, China. 5 Department of Tropical Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA. 6 Queensland Institute of Medical Research and Australian Centre for International Health & Nutrition, 300 Herston Road, Brisbane, Queensland 4029 Australia. 7 These authors contributed equally to this work. Correspondence should be addressed to Z.-G.H. (hanzg@chgc.sh.cn). Published online 14 September 2003; doi:10.1038/ng1236 Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource Wei Hu 1,2,7 , Qing Yan 1,7 , Da-Kang Shen 1,3,7 , Feng Liu 1,7 , Zhi-Dong Zhu 1,7 , Huai-Dong Song 4,7 , Xiang-Ru Xu 1,7 , Zhao-Jun Wang 3 , Yi-Ping Rong 1 , Ling-Chun Zeng 1 , Jian Wu 1 , Xin Zhang 1 , Ju-Jun Wang 2 , Xue-Nian Xu 2 , Sheng-Yue Wang 1 , Gang Fu 1 , Xiang-Lin Zhang 1 , Zhi-Qin Wang 1 , Paul J Brindley 5 , Donald P McManus 6 , Chun-Liang Xue 3 , Zheng Feng 2,7 , Zhu Chen 1,4 & Ze-Guang Han 1 Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies. NATURE GENETICS VOLUME 35 | NUMBER 2 | OCTOBER 2003 139 © 2003 Nature Publishing Group http://www.nature.com/naturegenetics