Article open access publication

The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

Diversity, MDPI, ISSN 1424-2818

Volume 11, 8, 2019

DOI:10.3390/d11080131, Dimensions: pub.1120310410,



  1. (1) University of Porto, grid.5808.5
  2. (2) Smithsonian Conservation Biology Institute, grid.419531.b
  3. (3) Smithsonian Institution, grid.1214.6
  4. (4) Nova Southeastern University, grid.261241.2
  5. (5) Saint Petersburg State University, grid.15447.33
  6. (6) Beijing Genomics Institute, grid.21155.32
  7. (7) Kunming Institute of Zoology, grid.419010.d
  8. (8) University of Copenhagen, grid.5254.6, KU
  9. (9) Howard Hughes Medical Institute, grid.413575.1
  10. (10) Laboratory of Neurogenetics of Language, Box 54, Rockefeller University, New York, NY 10065, USA


The vertebrate toll-like receptor (TLRs) supergene family is a first-line immune defense against viral and non-viral pathogens. Here, comparative evolutionary-genomics of 79 vertebrate species (8 mammals, 48 birds, 11 reptiles, 1 amphibian, and 11 fishes) revealed differential gain/loss of 26 TLRs, including 6 (TLR3, TLR7, TLR8, TLR14, TLR21, and TLR22) that originated early in vertebrate evolution before the diversification of Agnatha and Gnathostomata. Subsequent dynamic gene gain/loss led to lineage-specific diversification with TLR repertoires ranging from 8 subfamilies in birds to 20 in fishes. Lineage-specific loss of TLR8-9 and TLR13 in birds and gains of TLR6 and TLR10-12 in mammals and TLR19-20 and TLR23-27 in fishes. Among avian species, 5–10% of the sites were under positive selection (PS) (omega 1.5–2.5) with radical amino-acid changes likely affecting TLR structure/functionality. In non-viral TLR4 the 20 PS sites (posterior probability PP > 0.99) likely increased ability to cope with diversified ligands (e.g., lipopolysaccharide and lipoteichoic). For viral TLR7, 23 PS sites (PP > 0.99) possibly improved recognition of highly variable viral ssRNAs. Rapid evolution of the TLR supergene family reflects the host–pathogen arms race and the coevolution of ligands/receptors, which follows the premise that birds have been important vectors of zoonotic pathogens and reservoirs for viruses.

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Dimensions Citation Indicators

Times Cited: 5

Open Access Info

Pure Gold