Earlier research suggested great variation in the number of NLRs among the closely associated species [
35], and the number is not related to the size of the genome or the level of ploidy [
36]. However, more than 1,500 NLRs have been detected by analyzing the transcriptional and physical organization of the intracellular immune receptor repertory in bread wheat [
37]. More than 2,000 NLRs have been identified using the fully annotated reference genome of bread wheat [
25]. Several studies have identified 5,905 (98% identity) to 7,780 (100% identity) unique NLR signatures in the genomes of different wheat lines, emphasizing the complexity and size of immune receptor repertory guiding disease resistance [
1]. This may also demonstrate the relationship between NLR number and genome size and between NLR number and ploidy level. Generally, the NLR loci exist as singletons (isolated genes) or clusters (tightly linked, related genes) [
38]. Occasionally, the gene clusters include NBS-LRR gene copies from different phylogenetic clades [
39]. NLRs usually exhibit consistent clustering [
40]. In bread wheat, numerous NLRs are found grouped at the distal end of all chromosome arms and often co-localize with known disease-resistance loci [
25]. In such an arrangement, the gene products act together to trigger immunity, providing coregulatory benefits.
In plants, the NLR proteins are abundant and old [
41]. Gene duplications, followed by point mutation-induced DNA-sequence divergence and deletion and duplication of intragenic DNA repeats encoding blocks of leucine-rich elements, led to the origin of R-gene polymorphisms. Further, recombination uses this variation between related genes to alter the gene sequences [
42]. Due to the diversity and abundance of pathogens in different environments, plants face dynamic selection pressure from habitat pathogens during their evolution, which results in the inability to maintain stable distribution of NLR genes between and even within species [
10]. It has been found in research on different angiosperms that significant pathogen infection pressure has driven the expansion of NLR genes [
43,
44,
45]. In the study of wild emmer wheat, it was found that changes in the NLR gene appeared to be rapid within the species [
46]. Due to differences in the abundance of pathogenic bacteria in habitats, the population of wild wheat differentiated, with wild wheat growing in areas where powdery mildew was prevalent, evolving resistance to powdery mildew. As stated earlier, the clusters (medium and large) may vary greatly in their size among the ecotypes and cultivated varieties, indicating potential local adaptability [
47,
48]. For clusters containing highly homologous NLRs from a single family with few inversions, direct duplication of gene probably resulted in the original clustering; subsequently, increased rates of unequal crossing-over (UCO) during meiosis probably provided the material for rapid evolution and increased diversity in immune sensors, thereby expanding the cluster. Under different pressures, these clusters rapidly contract or expand, which explains the large variations in cluster patterns between ecotypes. However, the abundance of NLR genes is not solely beneficial; the more NLR genes plants maintain, the more health costs they incur [
49]. Under no or less pathogen selection pressure, various plant species have exhibited contraction of NLR genes [
50,
51], leading to significant variations in the number and diversity of NLR genes between or within species. Gene recombination is crucial for NLR diversification. Current evidence shows that the unconventional recombination (illegitimate recombination) between NLR genes is the main way to change the number of repeats of the LRR domain, which can cause a rapid increase or decrease in the repeat number of the LRR, further increasing the potential of NLR to recognize different effectors [
24]. In addition, if the NLR gene recombines with other genes (such as WRKY, NAC), it can cause the fusion of the domains of other genes to NLR, further enriching the diversity of NLR structure and function (
Figure 2B). For example, a WRKY domain is attached to the Arabidopsis NLR gene RRS1 at the C-terminus. Further research found that this gene fusion phenomenon is very common in plant NLR genes. In addition, some gene recombination events can also cause the loss of the NLR domain, resulting in truncated NLR (truncated NLR). Truncated NLRs are also ubiquitous in various plants and also play very important roles in plant immunity. Interestingly, although the domains of truncated NLRs are incomplete, they can also perform similar functions to intact NLRs: they can directly or indirectly recognize effectors and induce plant immunity [
14]. Taken together, gene duplication of NLRs provided diversity to cope with the infection of thousands of evolving pathogenic bacteria.