The virus most often reported in papaya (Carica papaya L.) is papaya ringspot (PRSV). The aim of this work was the molecular genomic characterization of a Mexican severe isolate of PRSV-P "Mex-VrPO" (isolate from the State of Veracruz in Paso de Ovejas) as well as its comparison with other isolates from other world regions. The linear, assembled, single-strand positive sense RNA genome of PRSV-P Mex-VrPO was 10320 nt in length (excluding the poly(A) tail) and contained a single large predicted ORF with 3344 aa. The comparative analysis of our PRSV isolates and five others reported before, showed the most variable proteins were P1, P3, 6 K and CP with 13-33%, 5-7%, 6-9% and 5-9% divergence respectively. The most conserved ones were CI, NIb and HC-Pro (2-3%, 3-5% and 4-5%). The phylogenetic analysis showed a close relation between the Mexican (Mex-VrPO) and Hawaiian (PRSV-P HA) isolates. This work provided the first opportunity to establish the foundation for (1) understanding whole genome and polyprotein variability between Asian and American PRSV isolates, and (2) elucidating major trends in the relative evolution of viral cistrons as deduced from in silico recombination analyses.