Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
Genetics and Genomics Academy, North Carolina State University, Raleigh, NC, USA.
Immunogenetics. 2023 Oct;75(5):465-478. doi: 10.1007/s00251-023-01315-7. Epub 2023 Aug 9.
Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate RAG- mediated adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here, we investigate the diversification of vertebrate toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the RAG-mediated adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively, these results provide an unparalleled perspective of TLR diversity and offer a ready framework for testing gene annotations in non-model species.
自 50 多年前首次发现以来，理解脊椎动物 RAG 介导的适应性免疫反应的进化一直是比较遗传学家的主要研究重点。然而，直到最近，适应性免疫反应的进化新颖性如何影响与先天免疫反应相关的受体多样性才受到相当少的关注。在这里，我们调查了脊椎动物 toll 样受体 (TLR) 的多样化，TLR 是生命之树上发现的最古老和最保守的先天免疫受体家族之一，整合了代表所有主要脊椎动物谱系的基因组数据，并结合了来自最早分化的硬骨鱼谱系——多鳍鱼的新转录组数据。我们的分析揭示了反映 6 个主要 TLR 亚家族的 TLR 序列，TLR1、TLR3、TLR4、TLR5、TLR7 和 TLR11，以及目前尚未命名但在系统发育上明显不同的 TLR 分支。我们还发现了证据表明，在有颌脊椎动物 RAG 介导的适应性免疫反应兴起的同时，存在基因增益的脉冲，随后在白垩纪期间发生了快速的基因丢失。这些基因丢失主要集中在海洋硬骨鱼类中，与中白垩纪缺氧事件同步发生，这是海洋物种快速灭绝的时期。最后，我们揭示了多达 50%的 TLR 在硬骨鱼类、圆口类、两栖动物和软骨鱼类等类群中的系统发育位置与基因命名之间存在不匹配。总的来说，这些结果提供了 TLR 多样性的无与伦比的视角，并为在非模式物种中测试基因注释提供了现成的框架。
