Editing Symbiogenesis (section)

=== Gene transfer mechanisms ===

The mechanisms of gene transfer are not fully known; however, multiple hypotheses exist to explain this phenomenon. The possible mechanisms include the [[Complementary DNA]] (cDNA) hypothesis and the bulk flow hypothesis.<ref name="Timmis2004"/><ref name="Leister2005"/> 

The cDNA hypothesis involves the use of [[messenger RNA]] (mRNAs) to transport genes from organelles to the nucleus where they are converted to cDNA and incorporated into the genome.<ref name="Timmis2004"/><ref name="Leister2005"/> The cDNA hypothesis is based on studies of the genomes of flowering plants. Protein coding RNAs in mitochondria are spliced and edited using organelle-specific splice and editing sites. Nuclear copies of some mitochondrial genes, however, do not contain organelle-specific splice sites, suggesting a processed mRNA intermediate. The cDNA hypothesis has since been revised as edited mitochondrial cDNAs are unlikely to recombine with the nuclear genome and are more likely to recombine with their native mitochondrial genome. If the edited mitochondrial sequence recombines with the mitochondrial genome, mitochondrial splice sites would no longer exist in the mitochondrial genome. Any subsequent nuclear gene transfer would therefore also lack mitochondrial splice sites.<ref name="Timmis2004"/>

The bulk flow hypothesis is the alternative to the cDNA hypothesis, stating that escaped DNA, rather than mRNA, is the mechanism of gene transfer.<ref name="Timmis2004"/><ref name="Leister2005"/> According to this hypothesis, disturbances to organelles, including [[autophagy]] (normal cell destruction), [[gametogenesis]] (the formation of gametes), and cell stress release DNA which is imported into the nucleus and incorporated into the nuclear DNA using [[non-homologous end joining]] (repair of double stranded breaks).<ref name="Leister2005"/> For example, in the initial stages of endosymbiosis, due to a lack of major gene transfer, the host cell had little to no control over the endosymbiont. The endosymbiont underwent cell division independently of the host cell, resulting in many "copies" of the endosymbiont within the host cell. Some of the endosymbionts [[lysis|lysed]] (burst), and high levels of DNA were incorporated into the nucleus. A similar mechanism is thought to occur in tobacco plants, which show a high rate of gene transfer and whose cells contain multiple chloroplasts.<ref name="Barbrook2006"/> In addition, the bulk flow hypothesis is also supported by the presence of non-random clusters of organelle genes, suggesting the simultaneous movement of multiple genes.<ref name="Leister2005"/>

Ford Doolittle proposed that (whatever the mechanism) gene transfer behaves like a ratchet, resulting in unidirectional transfer of genes from the organelle to the nuclear genome.<ref name=":4">{{Cite journal |last=Ford Doolittle |first=W |date=1998-12-01 |title=You are what you eat: a gene transfer ratchet could account for bacterial genes in eukaryotic nuclear genomes |url=https://www.sciencedirect.com/science/article/pii/S0168952598014942 |journal=Trends in Genetics |volume=14 |issue=8 |pages=307–311 |doi=10.1016/S0168-9525(98)01494-2 |pmid=9724962 |issn=0168-9525}}</ref> When genetic material from an organelle is incorporated into the nuclear genome, either the organelle or nuclear copy of the gene may be lost from the population. If the organelle copy is lost and this is fixed, or lost through genetic drift, a gene is successfully transferred to the nucleus. If the nuclear copy is lost, horizontal gene transfer can occur again, and the cell can 'try again' to have successful transfer of genes to the nucleus.<ref name=":4"/> In this ratchet-like way, genes from an organelle would be expected to accumulate in the nuclear genome over evolutionary time.<ref name=":4"/>