Different levels of variability in subtypes 1b and 4a of hepatitis C viruses

We performed genetic and phenic analyses to evaluate nucleotide and amino-acid sequences of the amino-terminus of the E1 protein of HCV genotype 1b (extracted from databank) and 4a (characterised in this study). The non-synonymous (ka) mutation analysis demonstrated that the genome of genotype 1b was not saturated by variations, with a rate of transition/transversion (s/v) of 1.5, which is similar to the expected ratio (i.e., 2.0). The s/v ratio in genotype 4a isolates was lower (0.98), indicating saturation due long-term variability. Moreover, the genotype 1b sequences showed a higher number of ka mutations (s+v) (mean of 2.8 per sequence) than genotype 4a (mean of 1.5). The introduction of ka mutations resulted in a higher degree of amino acid variability in genotype 4a. In the genome of genotype 1b, each nucleotide mutation introduced new amino acids, with a Granthan distance of 3.35-42.5, whereas for genotype 4a the distances ranged from 48.8 to 102.1. The phenic analysis also indicated different and complex patterns of amino-acid substitution. Finally, diverse isoelectric points and hydrophobicity were predicted for the two genotypes, with a higher acidity for genotype 4a E1 proteins.