Pro That May Be Terrified Of BTK inhibitor

To compare sequences across their entire length, all predicted Lister 427 VSG nucleotide and protein sequences were aligned to their best match in TREU927 ( Fig. 3). The majority of sequences are very dissimilar to their closest match (98% identical over 50?bp (Supplementary Fig. 3). However, a small number are very similar; 20 of 2613 Lister 427 VSGs are >98% identical to ORFs in TREU927 across their entire length, 3 of which are 100% identical. Near identical sequences are also seen between Lister 427 and other T. brucei strains, including in T. brucei gambiense Dal927 (12 sequences >98% identical to the 68 VSGs in the v4.2 assemblies), and between 427 and T. evansi sequences (4?>?98% identical). By mapping the positions of these near-identical sequences onto the TREU927 genome assemblies, it can be seen that they are not clustered in ��protected�� locations in the genome, but are found throughout the VSG arrays (Supplementary Fig. 4). There is no correlation between conservation and distance from assembled chromosome ends (Supplementary Fig. 5; Spearman's rank correlation rho?=?0.054, p?=?0.2). If there were considerable recombination among silent VSGs, then these very highly similar sequences could represent sequences that by chance have not recombined. However, non-coding sequences alignable between Lister 427, TREU927 and Dal927 show ?1 SNP per 100?bp (excluding indels). Assuming that this proportion of SNPs is a reasonable estimate for divergence of VSG sequences, the probability of an individual orthologous pair remaining identical between stains is little cross-reactivity between expressed variants. Given these conditions, it might be expected that VSGs would be under diversifying pressure; that VSG genes would be fixing nucleotide substitutions that alter the protein sequence (non-synonymous mutations) faster than those that do not (synonymous mutations). However, comparing members of the Lister 427 VSGnome to their closest relatives in TREU927 shows that VSGs are actually under purifying selection, with a median dN/dS ratio of 0.45 ( Fig. 4).