Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds


Alcaide M, Edwards SV. Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds. Molecular Biology and Evolution [Internet]. 2011;28 (5) :1703-1715.


Toll-like receptors (TLR) are membrane-bound sensors of the innate immune system that recognize invariant and
distinctive molecular features of invading microbes and are also essential for initiating adaptive immunity in vertebrates.
The genetic variation at TLR genes has been directly related to differential pathogen outcomes in humans and livestock.
Nonetheless, new insights about the impact of TLRs polymorphism on the evolutionary ecology of infectious diseases can
be gained through the investigation of additional vertebrate groups not yet investigated in detail. In this study, we have
conducted the first characterization of the entire TLR multigene family (
10 genes) in non-model avian species. Using
primers targeting conserved coding regions, we aimed at amplifying large segments of the extracellular domains (275–435
aa) involved in pathogen recognition across seven phylogenetically diverse bird species. Our analyses suggest avian TLRs
are dominated by stabilizing selection, suggesting that slow rates of nonsynonymous substitution help preserve biological
function. Overall, mean values of
) at each TLR locus ranged from 0.196 to 0.517. However, we also found
patterns of positive selection acting on specific amino acid sites that could be linked to species-specific differences in
pathogen-associated molecular pattern recognition. Only 39 of 2,875 (
1.35%) of the codons analyzed exhibited
significant patterns of positive selection. At least one half of these positively selected codons can be mapped to putative
ligand-binding regions, as suggested by crystallographic structures of TLRs and their ligands and mutagenic analyses. We
also surveyed TLR polymorphism in wild populations of two bird species, the Lesser Kestrel
Falco naumanni
and the House
Carpodacus mexicanus
. In general, avian TLRs displayed low to moderate single nucleotide polymorphism levels and
an excess of silent nucleotide substitutions, but also conspicuous instances of positive directional selection. In particular,
TLR5 and TLR15 exhibited the highest degree of genetic polymorphism and the highest occurrence of nonconservative
amino acid substitutions. This study provides critical primers and a first look at the evolutionary patterns and implications
of TLR polymorphism in non-model avian species and extends the list of candidate loci for avian eco-immunogenetics
beyond the widely employed genes of the Major Histocompatibility Complex (MHC).

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Last updated on 05/24/2016