The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.
Bottom Line: Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families.Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family.Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.
Affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK email@example.com.Show MeSH
Mentions: For a comparative analysis of the ves gene repertoire in Babesia, we have produced high-quality, draft genome sequences for an additional strain of Babesia bovis (C9.1), four strains of B. bigemina (BOND, PR, BbiS3P and JG29) and two strains of B. divergens (1802A and Rouen1987). Descriptions of these strains and genome sequences are given in Table 1. Variation in genome size, gene number and the proportion of coding sequences are related to the quality of sequence assemblies and sequence contiguity, which is lower in sequences produced from short reads only. The larger number of coding sequences in B. bigemina relative to other species is due to unique gene duplications of conserved gene families and to a greater number of species-specific sequences encoding hypothetical proteins. Nonetheless, clustering analysis of B. bovis T2Bo coding sequences combined with corresponding data from B. bigemina BOND and B. divergens 1802A shows that gene content is consistent between species and that variation in surface antigens occurs against a largely conserved genomic background. Figure 1 shows that coding sequences seen in all species represent 78–88% of genes; 68–81% of all coding sequences show one-to-one correspondence (i.e. perfect orthology). Therefore, species-specific genes represent between 12.2 and 21.5% of genes in these species, with B. bigemina displaying the highest proportion of unique features. These are maximum estimates since they include predicted protein sequences that failed to cluster, and so potential mis-annotated sequences could be designated as species-specific genes. Ves gene homologs comprise a large proportion of these species-specific genes: 4.7% of all coding sequences in B. bovis T2Bo, 8% in B. bigemina BOND and 11.2% in B. divergens 1802A. While the remaining unique sequences are not homologous to ves1, they are often predicted to be expressed at the cell surface. This prediction is based upon their overall structural similarities with the B. bovis VESA1 polypeptides, which are placed on the erythrocyte surface (42), including a well-conserved C-terminal end and predicted transmembrane domain. This indicates that the most dynamic features of these genomes are associated with the host-pathogen interface.
Affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK firstname.lastname@example.org.