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Gene transfer agent
Gene transfer agents (GTAs) are DNA-containing virus-like particles that are produced by some bacteria and archaea and mediate horizontal gene transfer. Different GTA types have originated independently from viruses in several bacterial and archaeal lineages. These cells produce GTA particles containing short segments of the DNA present in the cell. After the particles are released from the producer cell, they can attach to related cells and inject their DNA into the cytoplasm. The DNA can then become part of the recipient cells' genome.
GTAs are classified as viriforms in the ICTV taxonomy. Among the GTAs mentioned by the article, RcGTA and DsGTA are now in the family Rhodogtaviriformidae, BaGTA in Bartogtaviriformidae, and VSH-1 in Brachygtaviriformidae. Dd1 and VTA do not yet have a classification.
The first GTA system was discovered in 1974, when mixed cultures of Rhodobacter capsulatus strains produced a high frequency of cells with new combinations of genes. The factor responsible was distinct from known gene-transfer mechanisms in being independent of cell contact, insensitive to deoxyribonuclease, and not associated with bacteriophage (phage) production. Because of its presumed function it was named gene transfer agent (GTA, now RcGTA) More recently other gene transfer agent systems have been discovered by incubating filtered (cell-free) culture medium with a genetically distinct strain.
The genes specifying GTAs are derived from phage DNA that has integrated into a host chromosome. Such prophages often acquire mutations that make them defective and unable to produce phage particles. Many bacterial genomes contain one or more defective prophages that have undergone more-or less-extensive mutation and deletion. Gene transfer agents, like defective prophages, arise by mutation of prophages, but they retain functional genes for the head and tail components of the phage particle (structural genes) and the genes for DNA packaging. The phage genes specifying its regulation and DNA replication have typically been deleted, and expression of the cluster of structural genes is under the control of cellular regulatory systems. Additional genes that contribute to GTA production or uptake are usually present at other chromosome locations. Some of these have regulatory functions, and others contribute directly to GTA production (e.g. the phage-derived lysis genes) or uptake and recombination (e.g. production of cell-surface capsule and DNA transport proteins) These GTA-associated genes are often under coordinated regulation with the main GTA gene cluster. Phage-derived cell-lysis proteins (holin and endolysin) then weaken the cell wall and membrane, allowing the cell to burst and release the GTA particles. The number of GTA particles produced by each cell is not known.
Some GTA systems appear to be recent additions to their host genomes, but others have been maintained for many millions of years. Where studies of sequence divergence have been done (dN/dS analysis), they indicate that the genes are being maintained by natural selection for protein function (i.e. defective versions are being eliminated).
However, the nature of this selection is not clear. Although the discoverers of GTA assumed that gene transfer was the function of the particles, the presumed benefits of gene transfer come at a substantial cost to the population. Most of this cost arises because GTA-producing cells must lyse (burst open) to release their GTA particles, but there are also genetic costs associated with making new combinations of genes because most new combinations will usually be less fit than the original combination. One alternative explanation is that GTA genes persist because GTAs are genetic parasites that spread infectiously to new cells. However this is ruled out because GTA particles are typically too small to contain the genes that encode them. For example, the main RcGTA cluster (see below) is 14 kb long, but RcGTA particles can contain only 4–5 kb of DNA.
Most bacteria have not been screened for the presence of GTAs, and many more GTA systems may await discovery. Although DNA-based surveys for GTA-related genes have found homologs in many genomes, but interpretation is hindered by the difficulty of distinguishing genes that encode GTAs from ordinary prophage genes.
In laboratory cultures, production of GTAs is typically maximized by particular growth conditions that induce transcription of the GTA genes; most GTAs are not induced by the DNA-damaging treatments that induce many prophages. Even under maximally inducing conditions only a small fraction of the culture produces GTAs, typically less than 1%.
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Gene transfer agent
Gene transfer agents (GTAs) are DNA-containing virus-like particles that are produced by some bacteria and archaea and mediate horizontal gene transfer. Different GTA types have originated independently from viruses in several bacterial and archaeal lineages. These cells produce GTA particles containing short segments of the DNA present in the cell. After the particles are released from the producer cell, they can attach to related cells and inject their DNA into the cytoplasm. The DNA can then become part of the recipient cells' genome.
GTAs are classified as viriforms in the ICTV taxonomy. Among the GTAs mentioned by the article, RcGTA and DsGTA are now in the family Rhodogtaviriformidae, BaGTA in Bartogtaviriformidae, and VSH-1 in Brachygtaviriformidae. Dd1 and VTA do not yet have a classification.
The first GTA system was discovered in 1974, when mixed cultures of Rhodobacter capsulatus strains produced a high frequency of cells with new combinations of genes. The factor responsible was distinct from known gene-transfer mechanisms in being independent of cell contact, insensitive to deoxyribonuclease, and not associated with bacteriophage (phage) production. Because of its presumed function it was named gene transfer agent (GTA, now RcGTA) More recently other gene transfer agent systems have been discovered by incubating filtered (cell-free) culture medium with a genetically distinct strain.
The genes specifying GTAs are derived from phage DNA that has integrated into a host chromosome. Such prophages often acquire mutations that make them defective and unable to produce phage particles. Many bacterial genomes contain one or more defective prophages that have undergone more-or less-extensive mutation and deletion. Gene transfer agents, like defective prophages, arise by mutation of prophages, but they retain functional genes for the head and tail components of the phage particle (structural genes) and the genes for DNA packaging. The phage genes specifying its regulation and DNA replication have typically been deleted, and expression of the cluster of structural genes is under the control of cellular regulatory systems. Additional genes that contribute to GTA production or uptake are usually present at other chromosome locations. Some of these have regulatory functions, and others contribute directly to GTA production (e.g. the phage-derived lysis genes) or uptake and recombination (e.g. production of cell-surface capsule and DNA transport proteins) These GTA-associated genes are often under coordinated regulation with the main GTA gene cluster. Phage-derived cell-lysis proteins (holin and endolysin) then weaken the cell wall and membrane, allowing the cell to burst and release the GTA particles. The number of GTA particles produced by each cell is not known.
Some GTA systems appear to be recent additions to their host genomes, but others have been maintained for many millions of years. Where studies of sequence divergence have been done (dN/dS analysis), they indicate that the genes are being maintained by natural selection for protein function (i.e. defective versions are being eliminated).
However, the nature of this selection is not clear. Although the discoverers of GTA assumed that gene transfer was the function of the particles, the presumed benefits of gene transfer come at a substantial cost to the population. Most of this cost arises because GTA-producing cells must lyse (burst open) to release their GTA particles, but there are also genetic costs associated with making new combinations of genes because most new combinations will usually be less fit than the original combination. One alternative explanation is that GTA genes persist because GTAs are genetic parasites that spread infectiously to new cells. However this is ruled out because GTA particles are typically too small to contain the genes that encode them. For example, the main RcGTA cluster (see below) is 14 kb long, but RcGTA particles can contain only 4–5 kb of DNA.
Most bacteria have not been screened for the presence of GTAs, and many more GTA systems may await discovery. Although DNA-based surveys for GTA-related genes have found homologs in many genomes, but interpretation is hindered by the difficulty of distinguishing genes that encode GTAs from ordinary prophage genes.
In laboratory cultures, production of GTAs is typically maximized by particular growth conditions that induce transcription of the GTA genes; most GTAs are not induced by the DNA-damaging treatments that induce many prophages. Even under maximally inducing conditions only a small fraction of the culture produces GTAs, typically less than 1%.