Editing Homeobox (section)

== Evolution ==

Phylogenetic analysis of homeobox gene sequences and homeodomain protein structures suggests that the last common ancestor of plants, fungi, and animals had at least two homeobox genes.<ref>{{cite journal | vauthors = Bharathan G, Janssen BJ, Kellogg EA, Sinha N | title = Did homeodomain proteins duplicate before the origin of angiosperms, fungi, and metazoa? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 25 | pages = 13749–53 | date = December 1997 | pmid = 9391098 | pmc = 28378 | doi = 10.1073/pnas.94.25.13749 | jstor = 43805 | bibcode = 1997PNAS...9413749B | doi-access = free }}</ref> Molecular evidence shows that some limited number of Hox genes have existed in the [[Cnidaria]] since before the earliest true [[Bilateria|Bilatera]], making these genes pre-[[Paleozoic]].<ref name="pmid17252055">{{cite journal | vauthors = Ryan JF, Mazza ME, Pang K, Matus DQ, Baxevanis AD, Martindale MQ, Finnerty JR | title = Pre-bilaterian origins of the Hox cluster and the Hox code: evidence from the sea anemone, Nematostella vectensis | journal = PLOS ONE | volume = 2 | issue = 1 | pages = e153 | date = January 2007 | pmid = 17252055 | pmc = 1779807 | doi = 10.1371/journal.pone.0000153 | bibcode = 2007PLoSO...2..153R | doi-access = free }}</ref> It is accepted that the three major animal ANTP-class clusters, Hox, ParaHox, and NK (MetaHox), are the result of segmental duplications. A first duplication created MetaHox and ProtoHox, the latter of which later duplicated into Hox and ParaHox. The clusters themselves were created by tandem duplications of a single ANTP-class homeobox gene.<ref>{{cite journal | vauthors = Garcia-Fernàndez J | title = The genesis and evolution of homeobox gene clusters | journal = Nature Reviews Genetics | volume = 6 | issue = 12 | pages = 881–92 | date = December 2005 | pmid = 16341069 | doi = 10.1038/nrg1723 | s2cid = 42823485 }}</ref> Gene duplication followed by [[neofunctionalization]] is responsible for the many homeobox genes found in eukaryotes.<ref name="pmid19734295">{{cite journal | vauthors = Mukherjee K, Brocchieri L, Bürglin TR | title = A comprehensive classification and evolutionary analysis of plant homeobox genes | journal = Molecular Biology and Evolution | volume = 26 | issue = 12 | pages = 2775–94 | date = December 2009 | pmid = 19734295 | pmc = 2775110 | doi = 10.1093/molbev/msp201 }}</ref><ref>{{cite journal | vauthors = Holland PW | title = Evolution of homeobox genes | journal = Wiley Interdisciplinary Reviews: Developmental Biology | volume = 2 | issue = 1 | pages = 31–45 | date = 2013 | pmid = 23799629 | doi = 10.1002/wdev.78 | s2cid = 44396110 }}</ref> Comparison of homeobox genes and gene clusters has been used to understand the evolution of genome structure and body morphology throughout metazoans.<ref>{{Cite journal| vauthors = Ferrier DE |date=2016|title=Evolution of Homeobox Gene Clusters in Animals: The Giga-Cluster and Primary vs. Secondary Clustering|journal=Frontiers in Ecology and Evolution|language=en|volume=4|doi=10.3389/fevo.2016.00036|issn=2296-701X|doi-access=free|hdl=10023/8685|hdl-access=free}}</ref>