Editing Evolutionary developmental biology (section)

==The control of body structure==

===Deep homology===
{{Further|Deep homology}}
Roughly spherical eggs of different animals give rise to unique morphologies, from jellyfish to lobsters, butterflies to elephants. Many of these organisms share the same structural genes for body{{hyp}}building<!--nothing to do with steroids and gyms--> proteins like collagen and enzymes, but biologists had expected that each group of animals would have its own rules of development. The surprise of evo-devo is that the shaping of bodies is controlled by a rather small percentage of genes, and that these regulatory genes are ancient, shared by all animals. The [[giraffe]] does not have a gene for a long neck, any more than the [[elephant]] has a gene for a big body. Their bodies are patterned by a system of switching which causes development of different features to begin earlier or later, to occur in this or that part of the embryo, and to continue for more or less time.<ref name=CarrollNatHist/>

The puzzle of how embryonic development was controlled began to be solved using the fruit fly ''[[Drosophila melanogaster]]'' as a [[model organism]]. The step-by-step control of [[Drosophila embryogenesis|its embryogenesis]] was visualized by attaching [[fluorescence|fluorescent]] dyes of different colours to specific types of protein made by genes expressed in the embryo.<ref name=CarrollNatHist/> A dye such as [[green fluorescent protein]], originally from [[Aequorea victoria|a jellyfish]], was typically attached to an [[antibody]] specific to a fruit fly protein, forming a precise indicator of where and when that protein appeared in the living embryo.<ref>{{Cite web |date=2015 |title=Fluorescent Probes |url=https://www.thermofisher.com/uk/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/fluorescent-probes.html# |access-date=12 October 2016 |publisher=ThermoFisher Scientific}}</ref>

[[File:PAX6 Phenotypes Washington etal PLoSBiol e1000247.png|thumb|upright=1.3|The ''[[pax-6]]'' gene controls development of eyes of different types across the animal kingdom.]]<!--actually what we need here is a pic of 3 eyes from diff. phyla, as in the "CarrollNatHist" ref - arthropod, squid, vertebrate-->
Using such a technique, in 1994 [[Walter Gehring]] found that the ''[[pax-6]]'' gene, vital for forming the eyes of fruit flies, exactly matches an eye-forming gene in mice and humans. The same gene was quickly found in many other groups of animals, such as [[squid]], a [[cephalopod]] [[mollusc]]. Biologists including [[Ernst Mayr]] had believed that eyes had arisen in the animal kingdom at least 40 times, as the anatomy of different types of eye varies widely.<ref name=CarrollNatHist/> For example, the fruit fly's [[compound eye]] is made of hundreds of small lensed structures ([[ommatidia]]); the [[human eye]] has a [[blind spot (vision)|blind spot]] where the [[optic nerve]] enters the eye, and the nerve fibres run over the surface of the [[retina]], so light has to pass through a layer of nerve fibres before reaching the detector cells in the retina, so the structure is effectively "upside-down"; in contrast, the cephalopod eye has the retina, then a layer of nerve fibres, then the wall of the eye "the right way around".<ref name="Land1992">{{Cite journal |last=Land |first=M. F. |last2=Fernald |first2=R. D. |year=1992 |title=The evolution of eyes |journal=[[Annual Review of Neuroscience]] |volume=15 |pages=1–29 |doi=10.1146/annurev.ne.15.030192.000245 |pmid=1575438}}</ref> The evidence of ''pax-6'', however, was that the same genes controlled the development of the eyes of all these animals, suggesting that they all evolved from a common ancestor.<ref name=CarrollNatHist/> [[Evo-devo gene toolkit|Ancient genes]] had been [[conserved sequence|conserved through millions of years of evolution]] to create dissimilar structures for similar functions, demonstrating [[deep homology]] between structures once thought to be purely analogous.<ref name=Stanislav1997/><ref name="Pichaud">{{Cite journal |last=Pichaud |first=Franck |last2=Desplan |first2=Claude |date=August 2002 |title=Pax genes and eye organogenesis |journal=Current Opinion in Genetics & Development |volume=12 |issue=4 |pages=430–434 |doi=10.1016/S0959-437X(02)00321-0 |pmid=12100888}}</ref> This notion was later extended to the evolution of [[embryogenesis]]<ref name="Drost 2017 69–75">{{Cite journal |last=Drost |first=Hajk-Georg |last2=Janitza |first2=Philipp |last3=Grosse |first3=Ivo |last4=Quint |first4=Marcel |year=2017 |title=Cross-kingdom comparison of the developmental hourglass |journal=Current Opinion in Genetics & Development |volume=45 |pages=69–75 |doi=10.1016/j.gde.2017.03.003 |pmid=28347942 |doi-access=free}}</ref> and has caused a radical revision of the meaning of homology in evolutionary biology.<ref name="Stanislav1997">{{Cite journal |last=Tomarev |first=Stanislav I. |last2=Callaerts |first2=Patrick |last3=Kos |first3=Lidia |last4=Zinovieva |first4=Rina |last5=Halder |first5=Georg |last6=Gehring |first6=Walter |last7=Piatigorsky |first7=Joram |year=1997 |title=Squid Pax-6 and eye development |journal=Proceedings of the National Academy of Sciences |volume=94 |issue=6 |pages=2421–2426 |bibcode=1997PNAS...94.2421T |doi=10.1073/pnas.94.6.2421 |pmc=20103 |pmid=9122210 |doi-access=free}}</ref><ref name=Pichaud/><ref name=Carroll_2008/>

===Gene toolkit===
{{Main|Evo-devo gene toolkit}}
{{Further|Plant evolutionary developmental biology}}

[[File:Hoxgenesoffruitfly.svg|thumb|upright=1.25|Expression of [[Hox gene|homeobox (Hox) genes]] in the fruit fly]]

A small fraction of the genes in an organism's genome control the organism's development. These genes are called the developmental-genetic toolkit. They are highly conserved among [[Phylum|phyla]], meaning that they are ancient and very similar in widely separated groups of animals. Differences in deployment of toolkit genes affect the body plan and the number, identity, and pattern of body parts. Most toolkit genes are parts of [[signalling pathway]]s: they encode [[transcription factor]]s, [[cell adhesion]] proteins, cell surface [[receptor (biochemistry)|receptor]] proteins and signalling [[Ligand (biochemistry)|ligands]] that bind to them, and secreted [[morphogens]] that diffuse through the embryo. All of these help to define the fate of undifferentiated cells in the embryo. Together, they generate the patterns in time and space which shape the embryo, and ultimately form the [[body plan]] of the organism. Among the most important toolkit genes are the [[Hox gene|''Hox'' genes]]. These transcription factors contain the [[homeobox]] protein-binding DNA motif, also found in other toolkit genes, and create the basic pattern of the body along its front-to-back axis.<ref name=Carroll_2008/>
Hox genes determine where repeating parts, such as the many [[vertebra]]e of [[snake]]s, will grow in a developing embryo or larva.<ref name=CarrollNatHist/> ''Pax-6'', already mentioned, is a classic toolkit gene.<ref>{{Cite journal |last=Xu, P.X. |last2=Woo, I. |last3=Her, H. |last4=Beier, D. R. |last5=Maas, R. L. |year=1997 |title=Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode |journal=Development |volume=124 |issue=1 |pages=219–231 |doi=10.1242/dev.124.1.219 |pmid=9006082}}</ref> Although other toolkit genes are involved in establishing the plant [[bodyplan]],<ref>{{Cite journal |last=Quint |first=Marcel |last2=Drost |first2=Hajk-Georg |last3=Gabel |first3=Alexander |last4=Ullrich |first4=Kristian Karsten |last5=Bönn |first5=Markus |last6=Grosse |first6=Ivo |date=2012-10-04 |title=A transcriptomic hourglass in plant embryogenesis |journal=Nature |volume=490 |issue=7418 |pages=98–101 |bibcode=2012Natur.490...98Q |doi=10.1038/nature11394 |issn=0028-0836 |pmid=22951968 |s2cid=4404460}}</ref> [[homeobox]] genes are also found in plants, implying they are common to all [[eukaryote]]s.<ref name="pmid19734295">{{Cite journal |last=Mukherjee |first=K. |last2=Brocchieri, L. |last3=Bürglin, T.R. |date=December 2009 |title=A comprehensive classification and evolutionary analysis of plant homeobox genes |journal=Molecular Biology and Evolution |volume=26 |issue=12 |pages=2775–94 |doi=10.1093/molbev/msp201 |pmc=2775110 |pmid=19734295}}</ref><ref name="pmid9336443">{{Cite journal |last=Bürglin, T.R. |date=November 1997 |title=Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals |journal=Nucleic Acids Research |volume=25 |issue=21 |pages=4173–80 |doi=10.1093/nar/25.21.4173 |pmc=147054 |pmid=9336443}}</ref><ref name="pmid17501745">{{Cite journal |last=Derelle |first=R. |last2=Lopez, P. |last3=Le Guyader, H. |last4=Manuel, M. |year=2007 |title=Homeodomain proteins belong to the ancestral molecular toolkit of eukaryotes |journal=Evolution & Development |volume=9 |issue=3 |pages=212–9 |doi=10.1111/j.1525-142X.2007.00153.x |pmid=17501745 |s2cid=9530210}}</ref>

===The embryo's regulatory networks===
{{Further|Regulation of gene expression|Transcriptional regulation}}

[[File:Gene Regulatory Network.jpg|thumb|upright=1.6|A [[gene regulatory network]]]]

The protein products of the regulatory toolkit are reused not by duplication and modification, but by a complex mosaic of [[pleiotropy]], being applied unchanged in many independent developmental processes, giving pattern to many dissimilar body structures.<ref name=Carroll_2008/> The loci of these pleiotropic toolkit genes have large, complicated and modular [[cis-regulatory element]]s. For example, while a non-pleiotropic [[rhodopsin]] gene in the fruit fly has a cis-regulatory element just a few hundred [[base pair]]s long, the pleiotropic [[eyeless]] cis-regulatory region contains 6 cis-regulatory elements in over 7000 base pairs.<ref name=Carroll_2008/> The [[gene regulatory network|regulatory networks]] involved are often very large. Each regulatory protein controls "scores to hundreds" of cis-regulatory elements. For instance, 67 fruit fly transcription factors controlled on average 124 target genes each.<ref name=Carroll_2008/> All this complexity enables genes involved in the development of the embryo to be switched on and off at exactly the right times and in exactly the right places. Some of these genes are structural, directly forming enzymes, tissues and organs of the embryo. But many others are themselves regulatory genes, so what is switched on is often a precisely-timed cascade of switching, involving turning on one developmental process after another in the developing embryo.<ref name=Carroll_2008/>

[[File:Drosophila early embryo protein gradients.svg|thumb|upright=1.2|left|Gene product distributions along the long axis of the early embryo of a [[Drosophila melanogaster|fruit fly]]]]

Such a cascading regulatory network has been studied in detail in the [[Drosophila embryogenesis|development of the fruit fly embryo]]. The young embryo is oval in shape, like a [[rugby ball]]. A small number of genes produce [[messenger RNA]]s that set up concentration gradients along the long axis of the embryo. In the early embryo, the ''[[bicoid]]'' and ''hunchback'' genes are at high concentration near the anterior end, and give pattern to the future head and thorax; the ''caudal'' and ''[[nanos (gene)|nanos]]'' genes are at high concentration near the posterior end, and give pattern to the hindmost abdominal segments. The effects of these genes interact; for instance, the Bicoid protein blocks the translation of ''caudal''{{'s}} messenger RNA, so the Caudal protein concentration becomes low at the anterior end. Caudal later switches on genes which create the fly's hindmost segments, but only at the posterior end where it is most concentrated.<ref name="Russel">{{Cite book |last=Russel |first=Peter |title=iGenetics: a molecular approach |publisher=Pearson Education |year=2010 |isbn=978-0-321-56976-9 |pages=564–571}}</ref><ref name="Rivera">{{Cite journal |last=Rivera-Pomar |first=Rolando |last2=Jackle, Herbert |year=1996 |title=From gradients to stripes in Drosophila embryogenesis: Filling in the gaps |journal=Trends in Genetics |volume=12 |issue=11 |pages=478–483 |doi=10.1016/0168-9525(96)10044-5 |pmid=8973159}}</ref>

[[File:Gap gene expression.svg|thumb|upright=0.8|[[Gap gene]]s in the fruit fly are switched on by genes such as ''[[bicoid]]'', setting up stripes across the embryo which start to pattern the body's segments.]]

The Bicoid, Hunchback and Caudal proteins in turn regulate the transcription of [[gap gene]]s such as ''giant'', ''knirps'', ''Krüppel'', and ''tailless'' in a striped pattern, creating the first level of structures that will become segments.<ref name="Nusslein" /> The proteins from these in turn control the [[pair-rule gene]]s, which in the next stage set up 7 bands across the embryo's long axis. Finally, the segment polarity genes such as ''[[engrailed (gene)|engrailed]]'' split each of the 7 bands into two, creating 14 future segments.<ref name=Russel/><ref name=Rivera/>

This process explains the accurate conservation of toolkit gene sequences, which has resulted in deep homology and functional equivalence of toolkit proteins in dissimilar animals (seen, for example, when a mouse protein controls fruit fly development). The interactions of transcription factors and cis-regulatory elements, or of signalling proteins and receptors, become locked in through multiple usages, making almost any mutation deleterious and hence eliminated by natural selection.<ref name=Carroll_2008/>

The mechanism that sets up every [[animal]]'s front-back axis is the same, implying a common ancestor. There is a similar mechanism for the back-belly axis for [[bilateria]]n animals, but it is reversed between [[arthropod]]s and [[vertebrate]]s.<ref>{{Cite journal |last=De Robertis |first=Eddy |last2=Sasai |first2=Yoshiki |year=1996 |title=A common plan for dorsoventral patterning in Bilateria |journal=Nature |volume=380 |issue=6569 |pages=37–40 |bibcode=1996Natur.380...37D |doi=10.1038/380037a0 |pmid=8598900 |s2cid=4355458}}</ref> Another process, [[gastrulation]] of the embryo, is driven by [[Myosin II]] molecular motors, which are not conserved across species. The process may have been started by movements of sea water in the environment, later replaced by the evolution of tissue movements in the embryo.<ref>{{Cite journal |last=Farge |first=Emmanuel |year=2003 |title=Mechanical induction of twist in the Drosophila foregut/stomodeal primordium |journal=Current Biology |volume=13 |issue=16 |pages=1365–1377 |doi=10.1016/s0960-9822(03)00576-1 |pmid=1293230 |doi-access=free}}</ref><ref>{{Cite journal |last=Nguyen |first=Ngoc-Minh |last2=Merle |first2=Tatiana |display-authors=etal |year=2022 |title=Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota |journal=Frontiers in Cell and Developmental Biology |volume=10 |page=992371 |doi=10.3389/fcell.2022.992371 |pmc=9754125 |pmid=36531949 |doi-access=free}}</ref>