Episodic Positive Selection in the Evolution of Avian Toll-Like Receptor Innate Immunity Genes

Abstract

Toll-like receptors (TLRs) are a family of conserved pattern-recognition molecules responsible for initiating innate and acquired immune responses. Because they play a key role in host defence, these genes have received increasing interest in the evolutionary and population genetics literature, as their variation represents a potential target of adaptive evolution. However, the role of pathogen-mediated selection (i.e. episodic positive selection) in the evolution of these genes remains poorly known and has not been examined outside of mammals. A recent increase in the number of bird species for which TLR sequences are available has enabled us to examine the selective processes that have influenced evolution of the 10 known avian TLR genes. Specifically, we tested for episodic positive selection to identify codons that experience purifying selection for the majority of their evolution, interspersed with bursts of positive selection that may occur only in restricted lineages. We included up to 23 species per gene (mean = 16.0) and observed that, although purifying selection was evident, an average of 4.5% of codons experienced episodic positive selection across all loci. For four genes in which sequence coverage traversed both the extracellular leucine-rich repeat region (LRR) and transmembrane/intracellular domains of the proteins, increased positive selection was observed at the extracellular domain, consistent with theoretical predictions. Our results provide evidence that episodic positive selection has played an important role in the evolution of most avian TLRs, consistent with the role of these loci in pathogen recognition and a mechanism of host-pathogen coevolution.

Costs of immunity and their role in the range expansion of the house sparrow in Kenya

“…However, most of that work involved variation in the sequence of leucine-rich repeat regions of TLRs, not sequences influencing the regulation of expression (Sironi et al, 2015). Across birds, extensive evidence for episodic positive selection on TLR-4 leucine-rich repeat regions has been observed (Grueber et al, 2014). On a scale more comparable to our study, a genetic bottleneck at the time of introduction influenced variation in the TLR-4 exon sequence in a passerine introduced to New Zealand (Grueber et al, 2013).…”

Transposable elements are the primary source of novelty in primate gene regulation

“…4E; Supplemental File S2), such as RFX5, SMAD1, and EOMES. The rapid evolution of immune response genes and TFs is supported by many studies in vertebrates and in Drosophila melanogaster, demonstrating that while the central machinery of immune responses is strongly conserved, components of the extended molecular networks can evolve rapidly or diversify as a consequence of evolutionary competition between hosts and pathogens (Jansa et al 2003;Vallender and Lahn 2004;Sackton et al 2007;Obbard et al 2009;Schadt 2009;Grueber et al 2014;Lazzaro and Schneider 2014;Salazar-Jaramillo et al 2014;Zak et al 2014;Sironi et al 2015;Wertheim 2015). Ape-specific CREs are enriched for binding sites of TFs involved in liver function but also in brain and neural system proliferation and development (Fig.…”

Both Epistasis and Diversifying Selection Drive the Structural Evolution of the Ebola Virus Glycoprotein Mucin-Like Domain

“…We tested for evidence of episodic diversifying selection within the Ebola virus genome using MEME (15). Available methods for identifying sites which undergo pervasive selection (constant through time) are not always able to detect episodic (sporadic) selection (20). However, MEME, a tool for detecting site-specific diversifying selection, circumvents this issue of low sensitivity by identifying episodes of diversifying selection affecting a subset of branches at individual sites (21).…”