Root-knot nematodes (RKN) of the genus Meloidogyne constitute the most widely distributed and damaging group of plant-parasitic nematodes. Plant resistance (R) is currently the most effective and environmentally safe method to control these pests. The mode of reproduction of the major species, i.e., apomictic (= mitotic) parthenogenesis, should theoretically lead to clonal progenies. However, the recent emergence of new virulent biotypes, able to overcome plant R genes, indicates that variability does exist in these organisms. Experiments showed that selection for virulence was possible in RKN, which has important consequences for the management and durability of natural R genes in the field. To understand the molecular mechanisms involved in such selection, we have developed a differential strategy based on the comparative analysis of pairs of RKN near-isogenic lineages and recent results obtained in the laboratory are presented. Understanding how the genome of these nematodes is modified in response to the selective pressure of a plant R gene should provide further data on the putative role of non-meiotic events leading to stable genetic variation in these apomictic organisms.