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Balancing selection acting on haplotypes of bovine TLRs

Publication at Faculty of Science |
2022

Abstract

The TLR genes coding for Toll-like receptors of anti-bacterial series, namely, TLR1, -2, -4, -5 and -6, were resequenced in Czech Simmental (Czech Red). PacBio sequencing allowed us to determine haplotypes within the range of the designed amplicons.

A more general statistical reconstruction of haplotypes from individual reads was carried out in parallel. The PacBio read results demonstrated non-randomly distributed frequencies of haplotypes. 15 haplotypes revealed in amplicon 1 in the proximal part of the TLR2 transcript formed two distinct groups.

Similar results were found for the haplotypes obtained by statistical reconstruction in TLR2 and TLR5. Similar to direct reconstruction in TLR2, the trend for a bimodal distribution was stronger in proximal regions of the transcripts.

The bimodal clustering of TLR haplotypes was reported earlier in cattle and other animal models; however, a final interpretation of this disequilibrium is still missing. Alternating infectious agents might be a factor causing balancing selection.

Two different functions performed by the TLR2 gene or its product are another possible mechanism. An example of a dual function might be the formation of two kinds of heterodimers, TLR2/TLR1 and TLR2/TLR6.

Nevertheless, the association of the groups of haplotypes with the transcript proximal region suggests that the selection target is located in the 5' regulatory regions of the TLR genes, although functional interactions in the proximal part of the transcript cannot be excluded.