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AllEmbryoErvEvolutionEvolved For EvolvabilityFitnessFitness LandscapeGenomesInfluenzaLandscapePlacenta

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“In early primates, we can pinpoint a particular ERV integration event into the locus of the pancreatic amylase gene that conferred upon our ancestors the ability to express their amylase genes in the salivary gland. This heritable change provided for tissue-specific expression of the gene and gave us our sweet tooth. Here, the introduction of new gene regulatory DNA sequences close to the transcriptional start site of the amylase gene allowed salivary secretion of amylase. The resulting phenotype must have offered advantages to primates as they developed a diet containing more complex carbohydrates.”

Sweet Tooth
Book:Viruses: Agents of Evolutionary Invention
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“The researchers looked deeper into these observations, in hopes of gaining insight into the mechanisms underlying the high evolutionary rate and extraordinary immunologic plasticity of influenza HA. They probed in more detail the precise codons that are used by the virus to encode the influenza HA1 protein. The discriminated between codons on the basis of volatility. Each three-nucleotide codon is related by a single nucleotide change to nine 'mutational neighbours.' Of those nine mutations, some proportion change the codon to a synonymous codon and some change it to a nonsynonymous one, which directs the incorporation of a different amino acid into the protein. More volatile codons are those for which a larger proportion of those nine mutational neighbours encode an amino acid change. The use of particular codons in a gene at a frequency that is disproportionate to their random selection for encoding a chosen amino acid is termed codon bias. Such bias is common and is influenced by many factors, but here the collaborators found strong evidence for codon bias that was particular for and restricted to the amino acids making up the HA1 epitopes. Remarkably, they observed that influenza employs a disproportionate number of volatile codons in its epitope-coding sequences. There was a bias for the use of codons that had the fewest synonymous mutational neighbours. In other words, influenza HA1 appears to have optimized the speed with which it can change amino acids in its epitopes. Amino acid changes can arise from fewer mutational events. The antibody combining regions are optimized to use codons that have a greater likelihood to undergo nonsynonymous single nucleotide substitutions : they are optimized for rapid evolution.”

EvolutionVolatilityInfluenzaEvolved For EvolvabilityVolatile Codons
Book:Viruses: Agents of Evolutionary Invention
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“Such then is the nature of quasispecies : the density of the sequence cloud at any point in sequence space is determined by the relative fitness of the sequence; regions of the cloud representing sequences of lesser fitness will be less densely populated and those with higher fitness, most populated. Here lies the most powerful quality of viral quasispecies: the density distribution of fitness variants dictates that sequences are represented at frequencies in relation to their relative fitness. Genomes with lower fitness will replicate poorly, or not at all, and the fittest genomes will replicate most efficiently. It therefore follows that there is a large bias toward the production of well-adapted genotypes: there are more of them, and they undergo most replicative cycles. This can permit viruses to experience evolutionary adaptation at rates that are orders of magnitude higher than those that could be achieved by truly random unbiased mutation. Sequences rapidly condense around the fittest area of the sequence space. Should the environment change, and, therefore, selective pressures change, a quasispecies can opportunistically exploits its inherent adaptive potential. Genotypes rapidly and ever-faster gravitate toward the cloud's new notational center of gravity. Changes in the fitness landscape of the sequence space that is occupied by a quasispecies are the natural consequence of altered selective pressures operating on the virus population. Such alterations may be the consequence of changed immunologic pressures exerted by the host, the application of antiviral drug therapy, or even cross-species transmission requiring the virus to adapt to a new host. Genotypes that once occupied the 'central' space, reserved for the fittest genotypes, are reduced in frequency and now occupy the more sparsely populated fringes of the fitness landscape; the very edge of the sequence cloud if you will. Here too lies an advantage for a quasispecies: it has a memory. The once best-adapted genotypes, now at a fitness disadvantage, can persist in the quasispecies as minor sequence variants. Under circumstances of fluctuating selective pressures, the ability of the population to recall an 'old' genome variant is a great asset. The quasispecies can rapidly respond and adapt by plucking out a preexisting variant and quickly coalescing around it to recreate an optimal fitness landscape.”

LandscapeFitnessGenomesFitness LandscapeQuasispecies
Book:Viruses: Agents of Evolutionary Invention
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“ERV envelope genes possess unique properties that make them suitable for use in forming the placenta: they are fusogenic proteins and they have immunosuppresive properties. Eutherian (placental) mammals distinguish themselves from nonplacental animals in the ability of the female to nurture the fertilized ovum and growing embryo within the body. The placenta is a transient tissue of embryonic origin whose evolution made it unnecessary to partition the embryo into a protective egg, which matured outside the mother's body. It serves two purposes for the maturing embryo: it is a conduit for respiratory gasses and nourishment supplied by the mother, and it provides an environment of immune tolerance. The fetus is necessarily half-foreign tissue, an allograft within the mother. It draws half of its genetic, and hence antigenic, identity from maternal and half from paternal genes. If the fetus is to mature within the mother, it must be isolated from the maternal immune system such that a graft-versus-host response does not reject it. The placenta forms early after implantation of the embryo. Syncytins mediate the formation of a continuous fused layer of cells around the embryo, isolating it from the mother, yet allowing essential nutrients to traverse from the mother's system. Although the observations on human syncytin-1 and -2 were compelling, it was left to scientists to definitively link syncytins to placental formation by studying mice. Here two syncytins (dubbed A and B) from murine ERVs were implicated, and genetic experiments with mice defective in these genes confirmed that their dysfunction disrupted placental formation. Notably, however, syncytin-A and -B were not syntenic with the human syncytins. That is, the human and mouse genes are not descended fron common ancestral syncytins; they have arisen by separate ERV gene capture events from different families of ERV in human and mouse ancestors.”

PlacentaEmbryoErvRetroviral ProteinsSyncytins
Book:Viruses: Agents of Evolutionary Invention
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