On 2016 Dec 05, Donald Forsdyke commented:

SELECTIVE PRESSURE TO CONSERVE VIRUS SPECIES IDENTITY

The authors correctly note that "the most obvious parameter associated with G + C content is the strength of molecular hybridization of polynucleotide duplexes" (1). Such hybridization controls recombination, which is favored when there is close sequence resemblance between different co-infecting viruses ("complete alignment conserved"), and is impeded when there is less sequence resemblance ("complete alignment variable"). The latter anti-recombination activity can be considered in relation to speciation mechanisms that initiate and retain taxonomic differentiations. As recently noted by Meyer et al., allied species of "viruses that infect the same [host] species and cell types are thought to have evolved mechanisms to limit recombination." Without such limitations the genomes would blend and co-infectants would lose their independence as distinct viral species. Mechanisms overcoming this selective disadvantage include "divergences in nucleotide composition and RNA structure that are analogous to pre-zygotic barriers in plants and animals" (2).

Thus, a nucleic acid region may be "conserved," not only because it encodes a protein (i.e. there is "protein pressure" on the sequence), but because it has a specific nucleotide composition (e.g. "GC-pressure"). While protein pressure mainly affects the first and second codon positions, GC-pressure can affect all codon positions. Indeed, at first and second codon positions there may be conflict between pressures, especially when protein pressure is high (i.e. in regions where amino acid conservation is high); then GC-pressure is constrained to vary only at the more flexible third codon position. In contrast, when protein pressure is low (i.e. in regions where amino acid conservation is low), then GC-pressure has greater freedom to affect all codon positions.

If, to avoid recombination, there is selective pressure on one branch of a diverging line to decrease its GC%, then it would be predicted that "the GC% of nucleotides encoding conserved amino acid (AA) residues" would be "consistently higher than that of nucleotides encoding variable AAs," where the pressure to decrease GC% has fuller rein to encompass all three codon positions (1). Conversely, it would be predicted that when there is pressure on a diverging line to increase GC%, then it would be predicted that the GC% corresponding to conserved codons would be consistently lower than that of non-conserved codons (e.g. Ebolavirus).

For flavivirus "the mean G% of the core conserved AA residues is higher (35%) than that of the variable AA residues (28%), but the mean G3% of the core conserved AA residues (28%) is similar to that of the variable AA residues (29%)" (1). While consistent with the above views, there is need for information on C3% and relative frequencies of synonymous codons (e.g. the two cysteine codons correspond either to low or high GC%). More details of selective anti-recombination pressures are presented elsewhere (3, 4). Similar considerations may apply to codon biases and GC% among mycobacteriophages (5).

1.Klitting R, Gould EA & de Lamballerie X (2016) G + C content differs in conserved and variable amino acid residues of flaviviruses and other evolutionary groups. Infection, Genetics and Evolution 45: 332-340.Klitting R, 2016

2.Meyer JR, Dobias DT, Medina SJ, Servilio L, Gupta A, Lenski RE (2016) Ecological speciation of bacteriophage lambda in allopatry and sympatry. Science 354: 1301-1304. Meyer JR, 2016

3.Forsdyke (2014) Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy. Microbes & Infect16:96-103. Forsdyke DR, 2014

4.Forsdyke DR (2016) Evolutionary Bioinformatics, 3rd edition. Springer, New York.

5.Esposito LA, Gupta S, Streiter F, Prasad A, Dennehy JJ (2016). Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias. Microbiol Genomics 2(10), doi: 10.1099/mgen.0.000079. See arXiv preprint

On 2016 Dec 05, Donald Forsdyke commented:

SELECTIVE PRESSURE TO CONSERVE VIRUS SPECIES IDENTITY

The authors correctly note that "the most obvious parameter associated with G + C content is the strength of molecular hybridization of polynucleotide duplexes" (1). Such hybridization controls recombination, which is favored when there is close sequence resemblance between different co-infecting viruses ("complete alignment conserved"), and is impeded when there is less sequence resemblance ("complete alignment variable"). The latter anti-recombination activity can be considered in relation to speciation mechanisms that initiate and retain taxonomic differentiations. As recently noted by Meyer et al., allied species of "viruses that infect the same [host] species and cell types are thought to have evolved mechanisms to limit recombination." Without such limitations the genomes would blend and co-infectants would lose their independence as distinct viral species. Mechanisms overcoming this selective disadvantage include "divergences in nucleotide composition and RNA structure that are analogous to pre-zygotic barriers in plants and animals" (2).

Thus, a nucleic acid region may be "conserved," not only because it encodes a protein (i.e. there is "protein pressure" on the sequence), but because it has a specific nucleotide composition (e.g. "GC-pressure"). While protein pressure mainly affects the first and second codon positions, GC-pressure can affect all codon positions. Indeed, at first and second codon positions there may be conflict between pressures, especially when protein pressure is high (i.e. in regions where amino acid conservation is high); then GC-pressure is constrained to vary only at the more flexible third codon position. In contrast, when protein pressure is low (i.e. in regions where amino acid conservation is low), then GC-pressure has greater freedom to affect all codon positions.

If, to avoid recombination, there is selective pressure on one branch of a diverging line to decrease its GC%, then it would be predicted that "the GC% of nucleotides encoding conserved amino acid (AA) residues" would be "consistently higher than that of nucleotides encoding variable AAs," where the pressure to decrease GC% has fuller rein to encompass all three codon positions (1). Conversely, it would be predicted that when there is pressure on a diverging line to increase GC%, then it would be predicted that the GC% corresponding to conserved codons would be consistently lower than that of non-conserved codons (e.g. Ebolavirus).

For flavivirus "the mean G% of the core conserved AA residues is higher (35%) than that of the variable AA residues (28%), but the mean G3% of the core conserved AA residues (28%) is similar to that of the variable AA residues (29%)" (1). While consistent with the above views, there is need for information on C3% and relative frequencies of synonymous codons (e.g. the two cysteine codons correspond either to low or high GC%). More details of selective anti-recombination pressures are presented elsewhere (3, 4). Similar considerations may apply to codon biases and GC% among mycobacteriophages (5).

1.Klitting R, Gould EA & de Lamballerie X (2016) G + C content differs in conserved and variable amino acid residues of flaviviruses and other evolutionary groups. Infection, Genetics and Evolution 45: 332-340.Klitting R, 2016

2.Meyer JR, Dobias DT, Medina SJ, Servilio L, Gupta A, Lenski RE (2016) Ecological speciation of bacteriophage lambda in allopatry and sympatry. Science 354: 1301-1304. Meyer JR, 2016

3.Forsdyke (2014) Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy. Microbes & Infect16:96-103. Forsdyke DR, 2014

4.Forsdyke DR (2016) Evolutionary Bioinformatics, 3rd edition. Springer, New York.

5.Esposito LA, Gupta S, Streiter F, Prasad A, Dennehy JJ (2016). Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias. Microbiol Genomics 2(10), doi: 10.1099/mgen.0.000079. See arXiv preprint