Abstract：
The major histocompatibility complex (MHC) multigene family encodes key pathogen-recognition molecules of the vertebrate adaptive immune system. Hyper-polymorphism of MHC genes is de novo generated by point mutations, but new haplotypes may also arise by re-shuffling of existing variation through intra- and inter-locus gene conversion. Although the occurrence of gene conversion at the MHC has been known for decades, we still have limited understanding of its functional importance. Here, I took advantage of extensive genetic resources (~9000 sequences) to investigate broad scale macroevolutionary patterns in gene conversion processes at the MHC across nearly 200 avian species. Gene conversion was found to constitute a universal mechanism in birds, as 83% of species showed footprints of gene conversion at either MHC class and 25% of all allelic variants were attributed to gene conversion. Gene conversion processes were stronger at MHC-II than MHC-I, but inter-specific variation at both MHC classes was explained by similar evolutionary scenarios, reflecting fluctuating selection towards different optima and drift. Gene conversion showed uneven phylogenetic distribution across birds and was driven by gene copy number variation, supporting significant role of inter-locus gene conversion processes in the evolution of the avian MHC. Finally, MHC gene conversion was stronger in species with fast life histories (high fecundity) and in long-distance migrants, likely reflecting variation in population sizes and host-pathogen coevolutionary dynamics. The results provide a robust comparative framework for understanding macroevolutionary variation in gene conversion at the avian MHC and reinforce important contribution of this mechanism to functional MHC diversity.
摘要：
主要组织相容性复合物（MHC）多基因家族编码脊椎动物适应性免疫系统的关键病原体识别分子。MHC基因的超多态性是由点突变从头产生的，但是新的单倍型也可能通过基因座内和基因座间基因转换对现有变异进行重新改组而产生。尽管MHC基因转换的发生已有数十年的历史,我们对其功能重要性的理解仍然有限。这里,我利用广泛的遗传资源（〜9000序列）研究了近200种鸟类在MHC基因转换过程中的广泛宏观进化模式。基因转换在鸟类中被发现是一种普遍的机制，因为83%的物种在任一MHC类别显示基因转换的足迹,所有等位基因变异中有25%归因于基因转换.MHC-II的基因转换过程强于MHC-I,但是两种MHC类别的特异性变异被相似的进化情景解释，反映对不同最优和漂移的波动选择。基因转换在鸟类中显示出不均匀的系统发育分布，并且受基因拷贝数变异的驱动，支持基因座间基因转换过程在禽类MHC进化中的重要作用。最后,在具有快速生活史（高繁殖力）和远距离移民的物种中，MHC基因转换更强。可能反映了种群规模和宿主-病原体共进化动力学的变化。结果为理解禽类MHC基因转换中的宏观进化变异提供了一个强大的比较框架，并加强了该机制对功能MHC多样性的重要贡献。
