Application of Evolutionary and Comparative Pathogen Genomics to ECF Vaccinology

To improve genomic resources for Theileria parva, the cause of East Coast Fever. Objectives are to improve genome annotation of T. parva, in silico antigen identification and map of genetic variation. The T. parva genome consists of 4 chromosomes and 2 organellar DNAs, one in the mitochondrion and the other in the apicoplast. The reference T. parva Muguga genome is ~8.3 5 Mbp in length and encodes ~4,100 protein coding genes. Gene density is high and ragenic regions are short as are introns if they occur. Little is known about the control of gene expression but preliminary transcript data from the schizont stage of the parasite have been generated. However, these data are more than 7 years old and there has been little systematic effort to improve the annotation and gene models although there have been many advances in computational biology and many more apicomplexan genome sequences are now available including those of closely related Theileria and Babesia species. Studies of DNA sequence variation in T. parva are sparse and have focused on diversity in the few antigens. Although antigenic and sequence diversity is a hallmark of T. parva it is not currently known whether sequence polymorphisms are specific to some loci or if this represents a genome-wide phenomenon in part associated with high recombination rates. Whole genome wide studies of pathogens underpin modern approaches to many infectious diseases studies, the most relevant being for Plasmodium with implications for selection of candidate vaccine antigens, population structure and epidemiology.