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Genome Biol Evol
2014 Dec 04;71:81-95. doi: 10.1093/gbe/evu266.
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Constraint and adaptation in newt toll-like receptor genes.
Babik W, Dudek K, Fijarczyk A, Pabijan M, Stuglik M, Szkotak R, Zieliński P.
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Acute die-offs of amphibian populations worldwide have been linked to the emergence of viral and fungal diseases. Inter and intraspecific immunogenetic differences may influence the outcome of infection. Toll-like receptors (TLRs) are an essential component of innate immunity and also prime acquired defenses. We report the first comprehensive assessment of TLR gene variation for urodele amphibians. The Lissotriton newt TLR repertoire includes representatives of 13 families and is compositionally most similar to that of the anuran Xenopus. Both ancient and recent gene duplications have occurred in urodeles, bringing the total number of TLR genes to at least 21. Purifying selection has predominated the evolution of newt TLRs in both long (∼70 Ma) and medium (∼18 Ma) timescales. However, we find evidence for both purifying and positive selection acting on TLRs in two recently diverged (2-5 Ma) allopatric evolutionary lineages (Lissotriton montandoni and L. vulgaris graecus). Overall, both forms of selection have been stronger in L. v. graecus, while constraint on most TLR genes in L. montandoni appears relaxed. The differences in selection regimes are unlikely to be biased by demographic effects because these were controlled by means of a historical demographic model derived from an independent data set of 62 loci. We infer that TLR genes undergo distinct trajectories of adaptive evolution in closely related amphibian lineages, highlight the potential of TLRs to capture the signatures of different assemblages of pathogenic microorganisms, and suggest differences between lineages in the relative roles of innate and acquired immunity.
Fig. 1.—. A Bayesian tree showing the relationships among vertebrate TLRs. Amphibian TLRs are color coded by species.
Fig. 2.—. Comparison of the domain structure between newt and frog TLRs. TLR19 is absent in Xenopus and zebrafish structure is provided instead; abbreviations of protein domains: LRR NT, Leucine-rich repeat, N-terminal; LRR, Leucine-rich repeat; LRR CT, LRR C-terminal.
Fig. 3.—. The distribution of fitness effects of new mutations in 11 Lissotriton TLR genes.
Fig. 4.—. Nucleotide diversity and Tajima’s D in population data sets; Lm, Lissotriton montandoni, Lvg, L. vulgaris graecus; π, overall, πS, synonymous and πN, nonsynonymous nucleotide diversity; D, overall, DS, synonymous and DN, nonsynonymous Tajima’s D.
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