DOI: 10.5061/dryad.80p28
title: Data from: Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification

description: Background: Toll-like receptors (TLRs) are the frontline actors in the
 innate immune response to various pathogens and are expected to be targets
 of natural selection in species adapted to habitats with contrasting
 pathogen burdens. The recent publication of genome sequences of giraffe
 and okapi together afforded the opportunity to examine the evolution of
 selected TLRs in broad range of terrestrial ungulates and cetaceans during
 their complex habitat diversification. Through direct sequence comparisons
 and standard evolutionary approaches, the extent of nucleotide and protein
 sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5,
 TLR7, TLR9 and TLR10) between giraffe and closely related species was
 determined. In addition, comparison of the patterning of key TLR motifs
 and domains between giraffe and related species was performed. The
 quantification of selection pressure and divergence on TLRs among
 terrestrial ungulates and cetaceans was also performed. Results: Sequence
 analysis shows that giraffe has 94–99% nucleotide identity with okapi and
 cattle for all TLRs analyzed. Variations in the number of Leucine-rich
 repeats were observed in some of TLRs between giraffe, okapi and cattle.
 Patterning of key TLR domains did not reveal any significant differences
 in the domain architecture among giraffe, okapi and cattle. Molecular
 evolutionary analysis for selection pressure identifies positive selection
 on key sites for all TLRs examined suggesting that pervasive evolutionary
 pressure has taken place during the evolution of terrestrial ungulates and
 cetaceans. Analysis of positively selected sites showed some site to be
 part of Leucine-rich motifs suggesting functional relevance in
 species-specific recognition of pathogen associated molecular patterns.
 Notably, clade analysis reveals significant selection divergence between
 terrestrial ungulates and cetaceans in viral sensing TLR3. Mapping of
 giraffe TLR3 key substitutions to the structure of the receptor indicates
 that at least one of giraffe altered sites coincides with TLR3 residue
 known to play a critical role in receptor signaling activity. Conclusion:
 There is overall structural conservation in TLRs among giraffe, okapi and
 cattle indicating that the mechanism for innate immune response utilizing
 TLR pathways may not have changed very much during the evolution of these
 species. However, a broader phylogenetic analysis revealed signatures of
 adaptive evolution among terrestrial ungulates and cetaceans, including
 the observed selection divergence in TLR3. This suggests that long term
 ecological dynamics has led to species-specific innovation and functional
 variation in the mechanisms mediating innate immunity in terrestrial
 ungulates and cetaceans.
description: Control file for M8
 model in PAMLControl file for the
 positive selection M8 PAML model used to analyze Toll-like receptors
 (Table 1)M8.ctlControl file for M7 model in PAMLControl file for the selection null (M7) PAML model used to analyze Toll-like receptors (Table 1).M7.ctlSLR raw data for TLR2TLR2 raw results for site-wise likelihood analysis (Table 1).TLR2_SLR_out.txtSLR raw data for TLR3TLR3 raw results for site-wise likelihood analysis (Table 1).TLR3_SLR_out.txtSLR raw data for TLR4TLR4 raw results for site-wise likelihood analysis (Table 1).TLR4_SLR_out.txtSLR raw data for TLR5TLR5 raw results for site-wise likelihood analysis (Table 1).TLR5_SLR_out.txtSLR raw data for TLR7TLR7 raw results for site-wise likelihood analysis (Table 1).TLR7_SLR_out.txtSLR raw data for TLR9TLR9 raw results for site-wise likelihood analysis (Table 1).TLR9_SLR_out.txtSLR raw data for TLR10TLR10 raw results for site-wise likelihood analysis (Table 1).TLR10_SLR_out.txtTLRs alignments and treesRaw sequence alignments and trees used to perform selection analyses in TLRs (Table 1, Table 2 and Figure 3)Giraffe and okapi sequence fileRaw sequences for giraffe and okapi TLRs used in the analyses.Additional File 1.txt