Different zebrafish have varying numbers of NLR genes for immune defense, with many being duplicated. Fish from laboratory strains possess fewer NLRs than wild fish. Image credit: Claudio Müller (CC BY 4.0)
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.
