关键词: Danio rerio NLR NOD-like receptor PacBio copy number variation evolutionary biology genetics genomics immune genes zebrafish

Mesh : Zebrafish / genetics immunology Animals DNA Copy Number Variations

来  源:   DOI:10.7554/eLife.98058   PDF(Pubmed)

Abstract:
Copy number variation in large gene families is well characterized for plant resistance genes, but similar studies are rare in animals. The zebrafish (Danio rerio) has hundreds of NLR immune genes, making this species ideal for studying this phenomenon. By sequencing 93 zebrafish from multiple wild and laboratory populations, we identified a total of 1513 NLRs, many more than the previously known 400. Approximately half of those are present in all wild populations, but only 4% were found in 80% or more of the individual fish. Wild fish have up to two times as many NLRs per individual and up to four times as many NLRs per population than laboratory strains. In contrast to the massive variability of gene copies, nucleotide diversity in zebrafish NLR genes is very low: around half of the copies are monomorphic and the remaining ones have very few polymorphisms, likely a signature of purifying selection.
Humans and other animals have immune systems that protect them from bacteria, viruses and other potentially harmful microbes. Members of a family of genes known as the NLR family play various roles in helping to recognize and destroy these microbes. Different species have varying numbers of NLR genes, for example, humans have 22 NLRs, but fish can have hundreds. 400 have been found in the small tropical zebrafish, also known as zebra danios. Zebrafish are commonly used as model animals in research studies because they reproduce quickly and are easy to keep in fish tanks. Much of what we know about fish biology comes from studying strains of those laboratory zebrafish, including the 400 NLRs found in a specific laboratory strain. Many NLRs in zebrafish are extremely similar, suggesting that they have only evolved fairly recently through gene duplication. It remains unclear why laboratory zebrafish have so many almost identical NLRs, or if wild zebrafish also have lots of these genes. To find out more, Schäfer et al. sequenced the DNA of NLRs from almost 100 zebrafish from multiple wild and laboratory populations. The approach identified over 1,500 different NLR genes, most of which, were previously unknown. Computational modelling suggested that each wild population of zebrafish may harbour up to around 2,000 NLR genes, but laboratory strains had much fewer NLRs. The numbers of NLR genes in individual zebrafish varied greatly – only 4% of the genes were present in 80% or more of the fish. Many genes were only found in specific populations or single individuals. Together, these findings suggest that the NLR family has expanded in zebrafish as part of an ongoing evolutionary process that benefits the immune system of the fish. Similar trends have also been observed in the NLR genes of plants, indicating there may be an evolutionary strategy across all living things to continuously diversify large families of genes. Additionally, this work highlights the lack of diversity in the genes of laboratory animals compared with those of their wild relatives, which may impact how results from laboratory studies are used to inform conservation efforts or are interpreted in the context of human health.
摘要:
大基因家族中的拷贝数变异被很好地表征为植物抗性基因,但是类似的研究在动物中很少见。斑马鱼(Daniorerio)具有数百个NLR免疫基因,使这个物种成为研究这种现象的理想选择。通过对来自多个野生和实验室种群的93条斑马鱼进行测序,我们确定了总共1,513个NLR,比以前已知的400多。其中大约一半存在于所有野生种群中,但在80%或更多的个体鱼类中只发现了4%。野生鱼类每个个体的NLR数量是实验室菌株的两倍,每个种群的NLR数量是实验室菌株的四倍。与基因拷贝的巨大变异性相反,斑马鱼NLR基因的核苷酸多样性非常低:大约一半的拷贝是单态的,其余的具有很少的多态性,可能是净化选择的标志。
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