Lineage replacement accompanying duplication and rapid fixation of an RNA element in the nsP3 gene in a species of alphavirus

Abstract

A sequence of thirty-six nucleotides in the nsP3 gene of Ross River virus (RRV), coding for the amino acid sequence HADTVSLDSTVS, was duplicated some time between 1969 and 1979 coinciding with the appearance of a new lineage of this virus and with a major outbreak of Epidemic Polyarthritis among residents of the Pacific Islands. This lineage of RRV continues to circulate throughout Australia and both earlier lineages, which lacked the duplicated element, now are extinct. Multiple copies of several other elements also were observed in this region of the nsP3 gene in all lineages of RRV. Multiple copies of one of these, coding for the amino acid sequence P*P*PR, were detected in the C-terminal region of the nsP3 protein of all alphaviruses except those of African origin. The fixation of duplications and insertions in 3' region of nsP3 genes from all lineages of alphaviruses, suggests they provide some fitness advantage.

Fig. 1

Duplicated elements in the nsP3 protein/gene of Ross River virus strain F9073. (A) Duplicated amino acid sequences are represented in the same colour. Underlined sequences appear to be repeats within a repeat and are found nowhere else in nsP3. (B) Possible sites at which a 36 nucleotide element of the RRV T48 genome could have been inserted in the parental genome to give rise to the duplicated amino acid sequence. Amino acids coded by nucleotides of interest are shown above and below the nucleotide sequences. Codons which differ between RRV T48 (no repeat) and F9073 (duplicated element) are shown in pink. Similar nucleotide sequences flanking a putative insertion site are highlighted. Nucleotide numbering is from the 5′ end of the nsP3 gene.

Fig. 2

Predicted secondary structure of the region of the RRV nsP3 gene in which a 36 nucleotide element was duplicated. (A) RRV T48 (B) RRV F9073 with the element duplicated. Nucleotide numbering refers to the position in the nsP3 gene of the respective viruses.

Fig. 3

Variation in the amino acid sequences of nsP3 proteins of different lineages within families of alphaviruses. Repeated elements are shown in bold type and what appear to be inserts of foreign sequence are shaded in grey.

Fig. 3

Variation in the amino acid sequences of nsP3 proteins of different lineages within families of alphaviruses. Repeated elements are shown in bold type and what appear to be inserts of foreign sequence are shaded in grey.