Purifying Selection Shaping the Evolution of the Toll-like Receptor 2 TIR Domain in Brown Hares (Lepus Europaeus) from Europe and the Middle East

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2020 Apr 3

PMID 32236892

Authors

Milomir Stefanovic

Mihajla Djan

Nevena Velickovic

Yasin Demirbas

Ladislav Paule

Csongor Istvan Gedeon

Annika Posautz

Christoph Beiglbock

Anna Kubber-Heiss

Franz Suchentrunk

Affiliations

Soon will be listed here.

Abstract

Toll-like receptors (TLRs) are transmembrane proteins of the innate immune system, composed of the ectodomain involved in pathogen recognition and the intracellular Toll/interleukin-1 receptor (TIR) domain important for downstream signal transduction. Here, we analyze the genetic variability of TIR nucleotide and amino-acid sequences of the TLR2 gene in 243 brown hares from Europe and the Middle East and tested for the presence of selection signals and spatial structuring. TLR2 TIR domain sequences were PCR amplified and sequenced, while genotyping was performed by phasing. Genetic diversity indices were calculated in DnaSP and Arlequin, while presence of selection signals was tested using MEGA and the Datamonkey web server. The presence of spatial patterns in TIR sequence distribution was tested by spatial Principal Component Analysis (sPCA) in adegenet. A total of 13 haplotypes were revealed with haplotype diversity of 0.424, and nucleotide diversity (π) of 0.00138. Two spatial clusters were revealed: "Anatolia/Middle East" and "Europe". In Anatolia the two most prevalent amino-acid variants, A and B (the latter being the most ancestral) were maintained at similar frequencies; but in Europe a shift in genotype frequencies was observed as well as a higher number of nonsynonymous substitutions giving rise to novel amino-acid protein variants originating from the evolutionarily younger protein variant. Molecular diversity (haplotype and nucleotide diversity) indices were significantly higher in the "Anatolia/Middle East" cluster. A signal of purifying selection was detected acting on the TIR sequences.

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