New paper

Happy to announce that the paper “Signatures of balancing selection in toll-like receptor (TLRs) genes – novel insights from a free-living rodent” has just been published in Scientific Reports. >> pdf

sci_rep

Signatures of balancing selection in TLR genes

Selective pressure from parasites is considered a key selective force driving evolution of the components of the immune system. Since single component of the immune system may interact with many pathogens, and single pathogen may be recognized by multiple components of the immune system, to better understand the mechanisms of parasite-driven selection it is necessary to study multiple genes and multiple pathogens. In our recent paper we characterized polymorphism in seven toll-like receptors (TLRs) in free-living bank voles Myodes glareolus. TLRs are components of innate immune response presenting microbial motifs. We found positive values of Fu and Li’s D* in TLR2 and TLR5, and positive Tajima’s D in LRR regions within TLR 1 and TLR2 interacting with pathogens what suggested balancing selection. This finding was further supported by significant associations between amino-acid alleles of TLR1 and TLR5 and susceptibility to infection with blood parasite Bartonella. The selection patterns in TLRs presenting virus-derived motifs (TLR7 and TLR9) differed considerably from TLRs interacting with bacterial PAMPs. On contrary to highly variable TLRs presenting bacterial motifs, TLR7 and TLR9 had low polymorphism and displayed signatures of directional selection.

source:
Kloch A, Wenzel MA, Laetsch DR, Michalski O, Welc-Falęciak R, Piertney SB. Susceptibility to infections and selection acting in the Toll-like receptors (TLR) in a free-living rodent, Myodes glareolus. Under review

Intronic variance affect susceptibility to infection

First results of the NCN-founded project!

We genotyped a cytokine, lymphotoxin alpha (LTA), also known as tumor necrosis factor beta (TNF-β) and we identified several SNPs both in introns and exons within the gene.

The exonic polymorphism explained variation in susceptibility to infection with the nematode A. tetraptera, and intronic SNP variants explained a risk of infection with A. tetraptera, and blood parasites Bartonella sp. The exonic SNP significantly associated with a risk of infection was in strong linkage disequlibrium with two intronic SNPs. Moreover, SNPs affecting risk of infection with A. tetraptera and Bartonella sp were in strong LD with two MHC-DRB alleles, yet none of these MHC alleles was found to be associated with the risk of infection in a post-hoc analysis.

Our results reflects the complexity of associations between components of the immune system and confirms that a simplified, single-gene approach, does not provide a clear and comprehensive view upon its evolution. An importance of intronic variation suggest that we should broaden the scope of studies focused on host-parasite genetic interplay beyond commonly analysed coding parts of the genome, as not only exonic polymorphism is subject to parasite-driven selection.

PopGroup50

Preliminary analysis of polymorphism of TLR genes presented at 50th Population Genetics Group in Cambrige.
TLRs in bank voles differed a lot in the level of polymorphism, from least diverse TLR7 (only 3 SNPs per 1kB) to most diverse TLR2 (over 25 SNPs per 1kB). So far, there is no evidence for an uniform pattern of selection acting on TLRs, and while some TLRs evolve under purifying selection while others are rather under positive selection.