Independent evolution of overlapping polymerase and surface protein genes of hepatitis B virus

Abstract

The genome of hepatitis B virus (HBV) provides a striking example of gene overlapping. In particular, the surface protein gene S is overlapped completely by the polymerase gene P. Evolutionary constraints in overlapping genes have been demonstrated for many viruses, with one of the two overlapping genes being subjected to positive selection (adaptive evolution), while the other one is subjected to purifying selection. Yet, for HBV to persist successfully, adaptive evolution of both the P and S genes is essential. We propose that HBV employs a mechanism that allows the independent adaptive evolution of both genes. We hypothesize that (i) the adaptive evolution of P occurs via p1/s3 non-synonymous substitutions, which are synonymous in S, (ii) the adaptive evolution of S occurs via p3/s2 non-synonymous substitutions, which are synonymous in P, and (iii) p2/s1 substitutions are rare. Analysis of 450 HBV sequences demonstrated that this mechanism is operational in HBV evolution both within and among genotypes. Positions were identified in both genes where adaptive evolution is operational. Whilst significant parts of the P and S genes were subjected to positive selection, with the K a /K s ratio for either the P or the S gene being .1, there were only a few regions where the K a /K s ratios in both genes were .1. This mechanism of independent evolution of the overlapping regions could also apply to other viruses, taking into account the increased frequency of amino acids with a high level of degeneracy in the proteins encoded by overlapping genes of viruses.

Molecular variability and evolution of a natural population of tomato yellow leaf curl virus in Shanghai, China

“…For monopartite begomoviruses, C4 is a pathogenicity determinant that is involved in movement and suppression of host defense responses, whereas the homologues of C4 encoded by most NW begomoviruses do not play a role in pathogenicity. This strategy, which allows viruses to condense a maximal amount of information into short genomes, has been widely used by a number of animal and plant-infecting viruses (Zaaijer et al, 2007). Given the rapid spread of TYLCV in China, it will be interesting to monitor the evolutionary constraints in vivo in experimentally infected tomato plants.…”

Immune-Induced Evolutionary Selection Focused on a Single Reading Frame in Overlapping Hepatitis B Virus Proteins

“…Beyond the codon usage, the relative positions of the codons have been proposed to be important. Zaaijer et al (54) have shown that the overlapping surface and polymerase genes of HBV evolve independently. They showed that most of the replacement mutations occur in P1/S3 (the nucleotide in the first position in polymerase codons and in the third position in surface codons) and P3/S2, while P2/S1 mutations are very rare.…”

Characterization of a New World Monopartite Begomovirus Causing Leaf Curl Disease of Tomato in Ecuador and Peru Reveals a New Direction in Geminivirus Evolution

“…The distributions of synonymous and nonsynonymous mutations were analyzed with the SNAP program (www.hiv.lanl.gov) (43). The hypothesis of independent evolution in overlapping genes was tested as described by Zaaijer et al (44). Variation was assessed by determining the entropy values for individual amino acids and nucleotides by using the BioEdit software (45).…”

“…This explains how convergent evolution in AC4 genes of NW bipartite begomoviruses can generate AC4/C4 proteins with functional similarity to C4 counterparts in OW monopartite begomoviruses while maintaining the more conserved Rep protein sequence. This strategy, which allows for maximizing the viral genome size and maintaining differential rates of mutation in overlapping genes, is used by a range of animal and plant-infecting viruses (44).…”