Editing Symbiogenesis (section)

==From endosymbionts to organelles==

[[File:Serial endosymbiosis.svg|thumb|left|upright=2|An [[Eukaryote#Autogenous models|autogenous model]] of the origin of eukaryotic cells. Evidence now shows that a mitochondrion-less eukaryote has never existed, i.e. the nucleus was acquired at the same time as the mitochondria.<ref>{{cite journal | vauthors = Pisani D, Cotton JA, McInerney JO | title = Supertrees disentangle the chimerical origin of eukaryotic genomes | journal = Molecular Biology and Evolution | volume = 24 | issue = 8 | pages = 1752–1760 | date = August 2007 | pmid = 17504772 | doi = 10.1093/molbev/msm095 | doi-access = free }}</ref>]]

Biologists usually distinguish [[organelle]]s from [[endosymbiont]]s – whole organisms living inside other organisms – by their reduced [[genome size]]s.<ref name="Keeling 2008">{{cite journal |last1=Keeling |first1=P. J. |last2=Archibald |first2=J. M. |title=Organelle evolution: what's in a name? |journal=[[Current Biology]] |volume=18 |issue=8 |pages=R345-7 |date=April 2008 |pmid=18430636 |doi=10.1016/j.cub.2008.02.065 |s2cid=11520942 |doi-access=free |bibcode=2008CBio...18.R345K }}</ref> As an endosymbiont evolves into an organelle, most of its genes are transferred to the host cell [[genome]].<ref>{{cite book |last1=Syvanen |first1=Michael |last2=Kado |first2=Clarence I. |title=Horizontal Gene Transfer |date=30 January 2002 |publisher=[[Academic Press]] |page=405 |isbn=978-0126801262}}</ref> The host cell and organelle therefore need to develop a transport mechanism that enables the return of the [[protein]] products needed by the organelle but now manufactured by the cell.<ref name="Timmis2004"/> 

=== Free-living ancestors ===

[[Alphaproteobacteria]] were formerly thought to be the free-living organisms most closely related to mitochondria.<ref name="Timmis2004">{{cite journal |last1=Timmis |first1=Jeremy N. |last2=Ayliffe |first2=Michael A. |last3=Huang |first3=Chun Y. |last4=Martin |first4=William |author4-link=William F. Martin |title=Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes |journal=[[Nature Reviews Genetics]] |volume=5 |issue=2 |year=2004 |doi=10.1038/nrg1271 |pages=123–135|pmid=14735123 |s2cid=2385111 }}</ref> Later research indicates that mitochondria are most closely related to [[Pelagibacterales]] bacteria, in particular, those in the SAR11 clade.<ref>{{cite web |url=https://www.sciencedaily.com/releases/2011/07/110725190046.htm |title=Mitochondria Share an Ancestor With SAR11, a Globally Significant Marine Microbe |date=July 25, 2011 |website=ScienceDaily |access-date=26 July 2011}}</ref><ref>{{cite journal |last1=Thrash |first1=J. Cameron |last2=Boyd |first2=Alex |last3=Huggett |first3=Megan J. |last4=Grote |first4=Jana |last5=Carini |first5=Paul |last6=Yoder |first6=Ryan J. |last7=Robbertse |first7=Barbara |last8=Spatafora |first8=Joseph W. |last9=Rappé |first9=Michael S. |last10=Giovannoni |first10=Stephen J. |display-authors=3 |title=Phylogenomic evidence for a common ancestor of mitochondria and the SAR11 clade |journal=Scientific Reports |volume=1 |issue=1 |date=14 June 2011 |page=13 |doi=10.1038/srep00013 |pmid=22355532 |pmc=3216501 |bibcode=2011NatSR...1...13T }}</ref> 

[[Diazotrophs|Nitrogen-fixing]] filamentous [[cyanobacteria]] are the free-living organisms most closely related to plastids.<ref name="Timmis2004"/><ref name="Deusch">{{cite journal |last1=Deusch |first1=O. |last2=Landan |first2=G. |last3=Roettger |first3=M. |last4=Gruenheit |first4=N. |last5=Kowallik |first5=K. V. |last6=Allen |first6=J. F. |last7=Martin |first7=W. |last8=Dagan |first8=T.  |display-authors=3 |title=Genes of Cyanobacterial Origin in Plant Nuclear Genomes Point to a Heterocyst-Forming Plastid Ancestor |journal=Molecular Biology and Evolution |volume=25 |issue=4 |date=14 February 2008 |doi=10.1093/molbev/msn022 |pages=748–761|pmid=18222943 }}</ref><ref>{{cite journal |last1=Ochoa de Alda |first1=Jesús A. G. |last2=Esteban |first2=Rocío |last3=Diago |first3=María Luz |last4=Houmard |first4=Jean |display-authors=3 |title=The plastid ancestor originated among one of the major cyanobacterial lineages |journal=Nature Communications |volume=5 |issue=1 |date=15 September 2014 |page=4937 |doi=10.1038/ncomms5937 |pmid=25222494 |bibcode=2014NatCo...5.4937O |doi-access=free }}</ref>

Both cyanobacteria and alphaproteobacteria maintain a large (>6{{nbsp}}[[Megabase|Mb]]) genome encoding thousands of proteins.<ref name="Timmis2004"/> [[Plastid]]s and [[mitochondria]] exhibit a dramatic reduction in genome size when compared with their bacterial relatives.<ref name="Timmis2004"/> Chloroplast genomes in photosynthetic organisms are normally 120–200{{nbsp}}kb<ref name="LilaKoumandou2004">{{cite journal |last1=Lila Koumandou |first1=V. |last2=Nisbet |first2=R. Ellen R. |last3=Barbrook |first3=Adrian C. |last4=Howe |first4=Christopher J. |display-authors=3 |title=Dinoflagellate chloroplasts—where have all the genes gone? |journal=[[Trends in Genetics]] |volume=20 |issue=5 |pages=261–267 |date=May 2004 |pmid=15109781 |doi=10.1016/j.tig.2004.03.008 }}</ref> encoding 20–200 proteins<ref name="Timmis2004"/> and mitochondrial genomes in humans are approximately 16{{nbsp}}kb and encode 37 genes, 13 of which are proteins.<ref name="Taanman1999">{{cite journal |last=Taanman |first=J. W. |title=The mitochondrial genome: structure, transcription, translation and replication |journal=Biochimica et Biophysica Acta (BBA) - Bioenergetics |volume=1410 |issue=2 |pages=103–23 |date=February 1999 |pmid=10076021 |doi=10.1016/S0005-2728(98)00161-3 |doi-access=free }}</ref> Using the example of the freshwater [[Amoeba|amoeboid]], however, ''[[Paulinella]] chromatophora'', which contains [[chromatophore]]s found to be evolved from cyanobacteria, Keeling and Archibald argue that this is not the only possible criterion; another is that the host cell has assumed control of the regulation of the former endosymbiont's division, thereby synchronizing it with the cell's [[Cell division|own division]].<ref name="Keeling 2008"/> Nowack and her colleagues gene sequenced the chromatophore (1.02{{nbsp}}Mb) and found that only 867 proteins were encoded by these photosynthetic cells. Comparisons with their closest free living cyanobacteria of the genus ''[[Synechococcus]]'' (having a genome size 3{{nbsp}}Mb, with 3300 genes) revealed that chromatophores had undergone a drastic genome shrinkage. Chromatophores contained genes that were accountable for [[photosynthesis]] but were deficient in genes that could carry out other biosynthetic functions; this observation suggests that these endosymbiotic cells are highly dependent on their hosts for their survival and growth mechanisms. Thus, these chromatophores were found to be non-functional for organelle-specific purposes when compared with mitochondria and plastids. This distinction could have promoted the early [[evolution]] of photosynthetic organelles.<ref>{{cite journal |last1=Nowack |first1=E. C. |last2=Melkonian |first2=M. |last3=Glockner |first3=G. |title=Chromatophore genome sequence of Paulinella sheds light on acquisition of photosynthesis by eukaryotes |journal=Current Biology |volume=18 |issue=6 |pages=410–8 |date=March 2008 |pmid=18356055 |doi=10.1016/j.cub.2008.02.051 |s2cid=15929741 |doi-access=free |bibcode=2008CBio...18..410N }}</ref>

The loss of genetic autonomy, that is, the loss of many genes from endosymbionts, occurred very early in evolutionary time.<ref name="Barbrook2006">{{cite journal |last1=Barbrook |first1=Adrian C. |last2=Howe |first2=Christopher J. |last3=Purton |first3=Saul |title=Why are plastid genomes retained in non-photosynthetic organisms? |journal=Trends in Plant Science |volume=11 |issue=2 |pages=101–8 |date=February 2006 |pmid=16406301 |doi=10.1016/j.tplants.2005.12.004 }}</ref> Taking into account the entire original endosymbiont genome, there are three main possible fates for genes over evolutionary time. The first is the loss of functionally redundant genes,<ref name="Barbrook2006"/> in which genes that are already represented in the nucleus are eventually lost. The second is the [[horizontal gene transfer|transfer]] of genes to the nucleus, while the third is that genes remain in the organelle that was once an organism.<ref name="Timmis2004"/><ref name="Barbrook2006"/><ref name="Leister2005">{{cite journal |last=Leister |first=D. |title=Origin, evolution and genetic effects of nuclear insertions of organelle DNA |journal=Trends in Genetics |volume=21 |issue=12 |pages=655–63 |date=December 2005 |pmid=16216380 |doi=10.1016/j.tig.2005.09.004 |url=http://edoc.mpg.de/277780 |hdl=11858/00-001M-0000-0012-3B56-7 |hdl-access=free }}</ref><ref name="Keeling2004">{{cite journal |last=Keeling |first=P. J. |title=Diversity and evolutionary history of plastids and their hosts |journal=American Journal of Botany |volume=91 |issue=10 |pages=1481–93 |date=October 2004 |pmid=21652304 |doi=10.3732/ajb.91.10.1481 |doi-access=free }}</ref><ref name="Archibald2009">{{cite journal |last=Archibald |first=J. M. |title=The puzzle of plastid evolution |journal=Current Biology |volume=19 |issue=2 |pages=R81–R88 |date=January 2009 |pmid=19174147 |doi=10.1016/j.cub.2008.11.067 |s2cid=51989 |doi-access=free |bibcode=2009CBio...19..R81A }}</ref> The loss of autonomy and integration of the endosymbiont with its host can be primarily attributed to nuclear gene transfer.<ref name="Archibald2009"/> As organelle genomes have been greatly reduced over evolutionary time, [[nuclear gene]]s have expanded and become more complex.<ref name="Timmis2004"/> As a result, many plastid and mitochondrial processes are driven by nuclear encoded gene products.<ref name="Timmis2004"/> In addition, many nuclear genes originating from endosymbionts have acquired novel functions unrelated to their organelles.<ref name="Timmis2004"/><ref name="Archibald2009"/>

=== 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"/>