Abstract
The haplotype structure of anti-bacterial Toll-like receptor genes (TLR1, -2, -4, -5 and -6) in Czech Red Pied cattle was explored. Initially, single nucleotide polymorphisms were detected by hybrid resequencing that combined PacBio RSII and WGS with HiSeq X Ten. 15 haplotypes were directly revealed in TLR2 by amplicon sequences and two distinct holotype groups were detected using the Network program.
Clustering in TLR2 was independently confirmed for statistically reconstructed haplotypes. The bimodal distribution was also detectable in the haplotypes of TLR5 and -6, while only a trend was seen in TLR4 and -1.
The pattern is consistent with the previously reported clustering of TLR haplotypes in other cattle breeds. Fluctuating selection due to the prevalence of pathogens, although considered as a reason earlier, should lead to the loss of diversity due to the stochastic processes.
Similarly, three clusters of TLR2 haplotypes observed in bank vole (Myodes glareolus) were ascribed to the positive selection by Borrelia afzelii (Tschirren et al., Proc. R.
Soc. B 280:20130364, 2013).
The balancing selection in bovine TLR2 might originate from two different functions of heterodimers formed with the TLR1 and TLR6 products, although this view was not previously supported by protein modelling (ibid.). However, functional bifurcation corresponds not only to different interactions with bacterial lipopolysaccharides, but also with the endogenous vs. exogenous ligands (Song et al., Crit.
Rev. Eukaryot.
Gene. Expr. 29:37, 2019).
The TLR haplotype role will be further interpreted in the frame of the newly designed large amplicons.