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Abstract Elephants have evolved multiple TP53 copies through a retrotransposition event followed by successive duplications. Some of these TP53 retrogenes (RTGs) are expressed and hypothesized to have functional roles in cellular regulation. However, comparative genomic studies on TP53 evolution and function are limited due to scarce genomic data for elephants and other afrotherians. Most existing research relies on scaffold assemblies of Loxodonta africana (LoxAfr3 and LoxAfr4), with some focus on Elephas maximus chromosomal assembly. In this in silico study, we analyzed three elephant genomes to validate TP53 RTGs, assess their copy variation, and trace their evolution. For the first time we describe 29 TP53 RTGs in E. maximus versus 18-19 in L. africana . These copies show sequence variation, especially in the duplicated regions and their flanking repetitive elements. Chromosomal mapping in E. maximus revealed that two major classes of TP53 RTGs are consistently arranged in pairs on chromosome 27, which harbours 27 of the 29 identified copies. The observed distribution strongly supports an evolutionary model in which large-scale genomic segments, each encompassing at least two retrogenes of different groups, were duplicated early in the elephant lineage, driving the extensive amplification of TP53 RTGs, as suggested also by the patterns of the flanking repetitive elements. The TP53 RTGs expansion was followed by a unique inversion on chromosome 27 that separates the duplication clusters. Thus, this study enhances our understanding of the elephant’s multi-p53 system, linked to cancer resistance, body size, and Peto’s paradox, and supports ongoing research into functional aspects. Significance Statement This study uncovers the complex genomic architecture of elephant TP53 RTGs, which have diversified into two phylogenetically distinct types present in both African and Asian elephants. While both species share these 2 types, they differ substantially in copy number (18 in African versus 28 in Asian elephants), and in sequence variation, highlighting lineage-specific evolutionary trajectories. Detailed sequence analyses of the chromosomal organization of these copies in the Elephas maximus high-quality genome assembly, particularly the cluster on chromosome 27, indicates that they arose from stepwise duplications of extended genomic segments, which likely facilitated both the expansion and regulatory diversification of the TP53 RTGs repertoire. Comparative analysis with other mammals reveals an elephant-specific inversion that reorganized the expanded TP53 RTGs copies, creating a new genomic configuration that could have influenced the regulation and expression of some of the p53 RTGs. Therefore, this work advances our understanding of how evolutionary pressures shaped the landscape of TP53 RTGs and their flanking genetics elements in elephants. By identifying accurately the retrogene copy numbers, sequences and putative functional domains, it establishes a critical foundation for future studies investigating their functional roles in DNA damage and genome stability.