Editing Mycobacterium tuberculosis (section)

===Co-evolution with modern humans===
There are currently two narratives existing in parallel regarding the age of MTBC and how it has spread and co-evolved with humans through time. One study compared the ''M. tuberculosis'' phylogeny to a human mitochondrial genome phylogeny and interpreted these as being highly similar. Based on this, the study suggested that ''M. tuberculosis'', like humans, evolved in Africa and subsequently spread with anatomically modern humans out of Africa across the world. By calibrating the mutation rate of M. tuberculosis to match this narrative, the study suggested that MTBC evolved 40,000–70,000 years ago.<ref name="Comes et. al." /> Applying this time scale, the study found that the ''M. tuberculosis'' [[effective population size]] expanded during the [[Neolithic Demographic Transition]] (around 10,000 years ago) and suggested that ''M. tuberculosis'' was able to adapt to changing human populations and that the historical success of this pathogen was driven at least in part by dramatic increases in human host population density. It has also been demonstrated that after emigrating from one continent to another, a human host's region of origin is predictive of which TB lineage they carry,<ref name="pmid16477032">{{cite journal | vauthors = Gagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC, Narayanan S, Nicol M, Niemann S, Kremer K, Gutierrez MC, Hilty M, Hopewell PC, Small PM | title = Variable host-pathogen compatibility in Mycobacterium tuberculosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 8 | pages = 2869–73 | date = February 2006 | pmid = 16477032 | pmc = 1413851 | doi = 10.1073/pnas.0511240103 | bibcode = 2006PNAS..103.2869G | doi-access = free}}</ref><ref name="pmid15041743">{{cite journal | vauthors = Hirsh AE, Tsolaki AG, DeRiemer K, Feldman MW, Small PM | title = Stable association between strains of Mycobacterium tuberculosis and their human host populations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 14 | pages = 4871–76 | date = April 2004 | pmid = 15041743 | pmc = 387341 | doi = 10.1073/pnas.0305627101 | doi-access = free}}</ref> which could reflect either a stable association between host populations and specific ''M. tuberculosis'' lineages and/or social interactions that are shaped by shared cultural and geographic histories.

Regarding the congruence between human and ''M. tuberculosis'' phylogenies, a study relying on ''M. tuberculosis'' and human [[Y chromosome]] DNA sequences to formally assess the correlation between them, concluded that they are not congruent.<ref>{{cite journal | vauthors = Pepperell CS, Casto AM, Kitchen A, Granka JM, Cornejo OE, Holmes EC, Holmes EC, Birren B, Galagan J, Feldman MW | title = The role of selection in shaping diversity of natural M. tuberculosis populations | journal = PLOS Pathogens | volume = 9 | issue = 8 | pages = e1003543 | date = August 2013 | pmid = 23966858 | pmc = 3744410 | doi = 10.1371/journal.ppat.1003543 | doi-access = free}}</ref> Also, a more recent study which included genome sequences from ''M. tuberculosis'' complex members extracted from three 1,000-year-old Peruvian mummies, estimated that the [[most recent common ancestor]] of the ''M. tuberculosis'' complex lived only 4,000 – 6,000 years ago.<ref name=":2">{{cite journal | vauthors = Bos KI, Harkins KM, Herbig A, Coscolla M, Weber N, Comas I, Forrest SA, Bryant JM, Harris SR, Schuenemann VJ, Campbell TJ, Majander K, Wilbur AK, Guichon RA, Wolfe Steadman DL, Cook DC, Niemann S, Behr MA, Zumarraga M, Bastida R, Huson D, Nieselt K, Young D, Parkhill J, Buikstra JE, Gagneux S, Stone AC, Krause J | title = Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis | journal = Nature | volume = 514 | issue = 7523 | pages = 494–97 | date = October 2014 | pmid = 25141181 | pmc = 4550673 | doi = 10.1038/nature13591 | bibcode = 2014Natur.514..494B}}</ref> The ''M. tuberculosis'' evolutionary rate estimated by the Bos et al. study<ref name=":2" /> is also supported by a study on Lineage 4 relying on genomic [[Ancient DNA|aDNA]] sequences from Hungarian mummies more than 200 years old.<ref>{{cite journal | vauthors = Kay GL, Sergeant MJ, Zhou Z, Chan JZ, Millard A, Quick J, Szikossy I, Pap I, Spigelman M, Loman NJ, Achtman M, Donoghue HD, Pallen MJ | title = Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe | journal = Nature Communications | volume = 6 | issue = 1 | pages = 6717 | date = April 2015 | pmid = 25848958 | pmc = 4396363 | doi = 10.1038/ncomms7717 | bibcode = 2015NatCo...6.6717K}}</ref> In total, the evidence thus favors this more recent estimate of the age of the MTBC most recent common ancestor, and thus that the global evolution and dispersal of ''M. tuberculosis'' has occurred over the last 4,000–6,000 years.{{citation needed|date=May 2024}}

Among the seven recognized lineages of ''M. tuberculosis'', only two are truly global in their distribution: Lineages 2 and 4. Among these, Lineage 4 is the most well dispersed, and almost totally dominates in the Americas. Lineage 4 was shown to have evolved in or in the vicinity of Europe, and to have spread globally with Europeans starting around the 13th century.<ref name=":3">{{cite journal | vauthors = Brynildsrud OB, Pepperell CS, Suffys P, Grandjean L, Monteserin J, Debech N, Bohlin J, Alfsnes K, Pettersson JO, Kirkeleite I, Fandinho F, da Silva MA, Perdigao J, Portugal I, Viveiros M, Clark T, Caws M, Dunstan S, Thai PV, Lopez B, Ritacco V, Kitchen A, Brown TS, van Soolingen D, O'Neill MB, Holt KE, Feil EJ, Mathema B, Balloux F, Eldholm V | title = Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation | journal = Science Advances | volume = 4 | issue = 10 | pages = eaat5869 | date = October 2018 | pmid = 30345355 | pmc = 6192687 | doi = 10.1126/sciadv.aat5869}}</ref> This study also found that Lineage 4 tuberculosis spread to the Americas shortly after the European discovery of the continent in 1492, and suggests that this represented the first introduction of human TB on the continent (although animal strains have been found in human remains predating Columbus.<ref name=":2" /> Similarly, Lineage 4 was found to have spread from Europe to Africa during the [[Age of Discovery]], starting in the early 15th century.<ref name=":3" />

It has been suggested that ancestral mycobacteria may have infected early hominids in East Africa as early as three million years ago.<ref name="pmid16201017">{{cite journal | vauthors = Gutierrez MC, Brisse S, Brosch R, Fabre M, Omaïs B, Marmiesse M, Supply P, Vincent V | title = Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis | journal = PLOS Pathogens | volume = 1 | issue = 1 | pages = e5 | date = September 2005 | pmid = 16201017 | pmc = 1238740 | doi = 10.1371/journal.ppat.0010005 | doi-access = free}}</ref>

DNA fragments from ''M. tuberculosis'' and tuberculosis disease indications were present in human bodies dating from 7000 BC found at [[Atlit-Yam]] in the [[Levant]].<ref>{{cite journal | vauthors = Hershkovitz I, Donoghue HD, Minnikin DE, Besra GS, Lee OY, Gernaey AM, Galili E, Eshed V, Greenblatt CL, Lemma E, Bar-Gal GK, Spigelman M | title = Detection and molecular characterization of 9,000-year-old Mycobacterium tuberculosis from a Neolithic settlement in the Eastern Mediterranean | journal = PLOS ONE | volume = 3 | issue = 10 | pages = e3426 | date = 15 October 2008 | pmid = 18923677 | pmc = 2565837 | doi = 10.1371/journal.pone.0003426 | publisher = Public Library of Science (PLoS) | doi-access = free | bibcode = 2008PLoSO...3.3426H | veditors = Ahmed N}}</ref>