Unusual human G6P[6] rotavirus A (RVA) strains have been reported sporadically in Europe and Africa, but how they evolved was not fully understood. The whole genome of a Ghanaian G6P[6] strain designated PML1965 (2012) was analysed to understand how it evolved in Africa and to learn how its G6 VP7 gene was related to that of rotaviruses of human and artiodactyl origin. The genotype constellation of RVA/Human-wt/GHA/PML1965/2012/G6P[6] was G6-P-[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2. It shared sublineages with G6P[6] strains previously detected in Italy and Africa in all genome segments except the VP6 gene of a few Burkinabe and Cameroonian strains and both the VP6 and NSP4 genes of Guinea Bissau strains. The VP7 gene of the G6P[6] strains appeared to derive from those of human G6P[9] strains, and they were distantly related to the VP7 genes of artiodactyl G6 or human G6P[14] strains. The time of the most recent common ancestor of the VP7 sequences of G6P[6] strains was estimated to be the year 1998. The evolutionary rates of the VP7 genes in bovine and human G6 rotaviruses were 6.93 × 10(-4) and 3.42 × 10(-3) nucleotide substitutions site(-1) year(-1), respectively, suggesting an accelerated adaptive process in the new host. The sequences of the remaining 10 genome segments of PML1965 clustered with those of G2 and G8 human rotaviruses detected in Africa possessing the DS-1-like genetic background. In conclusion, PML1965 evolved from G2 or G8 RVA strains with DS-1-like background, acquiring the G6 VP7 gene from a human G6P[9] RVA and not from an artiodactyl G6 RVA strain.