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<meta name="description" content="We find there has been much more homeobox gene loss in the rodent evolutionary lineage than in the primate lineage. While humans have lost only the Msx3 gene, mice have lost Ventx, Argfx, Dprx, Shox, Rax2, LOC647589, Tprx1 and Nanognb. This analysis provides insight into the patterns of homeobox gen …"><meta name="keywords" content="pmid:21679462, PMC3141429, doi:10.1186/1471-2148-11-169, Research Support, Non-U.S. Gov&#x27;t, Ying-fu Zhong, Peter W H Holland, Amino Acid Sequence, Animals, Evolution, Molecular*, Gene Deletion, Genes, Homeobox*, Genetic Loci, Humans, Mice, Molecular Sequence Data, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="The dynamics of vertebrate homeobox gene evolution: gain and loss of genes in mouse and human lineages - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/21679462/"><meta property="og:description" content="We find there has been much more homeobox gene loss in the rodent evolutionary lineage than in the primate lineage. While humans have lost only the Msx3 gene, mice have lost Ventx, Argfx, Dprx, Shox, Rax2, LOC647589, Tprx1 and Nanognb. This analysis provides insight into the patterns of homeobox gen …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="The dynamics of vertebrate homeobox gene evolution: gain and loss of genes in mouse and human lineages - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/21679462/"><meta name="twitter:description" content="We find there has been much more homeobox gene loss in the rodent evolutionary lineage than in the primate lineage. While humans have lost only the Msx3 gene, mice have lost Ventx, Argfx, Dprx, Shox, Rax2, LOC647589, Tprx1 and Nanognb. This analysis provides insight into the patterns of homeobox gen …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21679462">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://bmcevolbiol.biomedcentral.com/articles/10.1186/1471-2148-11-169"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3196&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21679462&amp;db=pubmed&amp;nlmid=100966975"
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data-ga-action="BioMed Central"
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BioMed Central
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21679462/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21679462&amp;db=pubmed&amp;nlmid=100966975"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21679462"
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Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21679462/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21679462/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21679462" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21679462%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="HcM3cavTGGntbZzassKOgNO6CMmV5CaXYZw8P0YfghaX5qF05LnQKVkKaQ47YdIh"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
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The dynamics of vertebrate homeobox gene evolution: gain and loss of genes in mouse and human lineages
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Homeobox genes are a large and diverse group of genes, many of which play important roles in transcriptional regulation during embryonic development. Comparison of homeobox genes between species may provide insights into the evolution of developmental mechanisms.
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Here we report an extensive survey of human and mouse homeobox genes based on their most recent genome assemblies, providing the first comprehensive analysis of mouse homeobox genes and updating an earlier survey of human homeobox genes. In total we recognize 333 human homeobox loci comprising 255 probable genes and 78 probable pseudogenes, and 324 mouse homeobox loci comprising 279 probable genes and 45 probable pseudogenes (accessible at http://homeodb.zoo.ox.ac.uk). Comparison to partial genome sequences from other species allows us to resolve which differences are due to gain of genes and which are due to gene losses.
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We find there has been much more homeobox gene loss in the rodent evolutionary lineage than in the primate lineage. While humans have lost only the Msx3 gene, mice have lost Ventx, Argfx, Dprx, Shox, Rax2, LOC647589, Tprx1 and Nanognb. This analysis provides insight into the patterns of homeobox gene evolution in the mammals, and a step towards relating genomic evolution to phenotypic evolution.
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<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><b> Chromosomal distribution of human <i> DUX4- </i> like genes and mouse 'chromosome 10' Dux Genes… </b></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1
</strong>
<div class="figure-caption-contents"><b>Chromosomal distribution of human <i>DUX4-</i>like genes and mouse 'chromosome 10' Dux Genes</b>. (A) Twenty-three human <i>DUX4</i>-like sequences include four loci with predicted introns interrupting the coding sequence (orange arrows) and nineteen intronless sequences (grey arrows), most clustering on chromosomes 4, 10 and Y. One putative intron-containing locus at chromosome 10q26.3 is disrupted by a translocation or is the remnants of two loci. (B) The Dux gene on mouse chromosome 10 has been duplicated in tandem to generate three loci. Orientation of arrows indicates direction of transcription; small arrowheads indicate putative introns.</div>
</figcaption>
</figure>
<figure class="figure-item "
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
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<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><b> <i> DUXB </i> and <i> CPHX </i> loci in… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><b> <i> DUXB </i> and <i> CPHX </i> loci in mouse and human </b> . (A) Mouse <i> DUXB-like </i> (…</div>
</div>
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<strong class="figure-label">
Figure 2
</strong>
<div class="figure-caption-contents"><b><i>DUXB </i>and <i>CPHX </i>loci in mouse and human</b>. (A) Mouse <i>DUXB-like </i>(<i>Duxbl</i>, orange arrows) and <i>Cphx </i>(red arrows), together with a non-homeobox gene <i>Plac9 </i>(green arrows), have been duplicated giving three copies each at chromosome 14A3. (B) Human <i>Cphx</i>-related homeobox loci flank a <i>DUXBL </i>pseudogene and the <i>DUXB </i>gene on chromosomes 10 and 16 respectively, although the loci on chromosome 10 are disrupted (ragged boxes). <i>Anxa11 </i>(blue arrows) is not a homeobox genes. (C) Amino acid alignments; dots represent identical amino acids, dashes deletons/insertions and red characters conservative substitutions. Hs, <i>Homo sapiens</i>; Mm, <i>Mus musculus</i>.</div>
</figcaption>
</figure>
<figure class="figure-item "
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data-image-height="454"
data-image-alt="Figure 3"
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data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/49faf0a804cd/1471-2148-11-169-3.gif"
alt="Figure 3" />
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><b> Presence or absence of the… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><b> Presence or absence of the <i> NANOGNB </i> gene in mammalian genomes </b> . (A) The…</div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3
</strong>
<div class="figure-caption-contents"><b>Presence or absence of the <i>NANOGNB </i>gene in mammalian genomes</b>. (A) The deduced homeodomain sequence of human <i>NANOGNB </i>showing predicted alpha helical regions, compatible with folding into a homeodomain tertiary structure. (B) <i>NANOGNB </i>is located just 15 kb from the human <i>NANOG </i>gene at chromosome 12p13.31 (orange arrows). Orthologous genes at the syntenic position are present in horse and dog, but not in mouse and rat. Grey arrows indicate non-homeobox genes.</div>
</figcaption>
</figure>
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aria-describedby="figure-caption-3"
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data-image-alt="Figure 4"
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data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/33d79f635da3/1471-2148-11-169-4.gif"
alt="Figure 4" />
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<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><b> Absence of <i> LOC647589 </i> in the… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><b> Absence of <i> LOC647589 </i> in the mouse genome </b> . <i> LOC647589 </i> was detected in this…</div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents"><b>Absence of <i>LOC647589 </i>in the mouse genome</b>. <i>LOC647589 </i>was detected in this study at human chromosome 12q24.33. No annotation is found in genomes outside of human currently, although a homologous sequences is present in cow (chr17:46,768,917-46,783,902) and other mammals with available genome sequences, but not in mouse or rat. The orange arrow and box indicate homeobox loci; grey arrows indicate non-homeobox genes.</div>
</figcaption>
</figure>
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data-pmc-id="PMC3141429"
data-figure-id="F5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/64879fa8a724/1471-2148-11-169-5.gif"
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<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><b> Rhox (reproductive homeobox) gene clusters… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><b> Rhox (reproductive homeobox) gene clusters </b> . (A) Three Rhox loci are present in…</div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5
</strong>
<div class="figure-caption-contents"><b>Rhox (reproductive homeobox) gene clusters</b>. (A) Three Rhox loci are present in the human genome at chromosome Xq24. (B) Thirty-six Rhox loci are clustered in the mouse genome at chromosome X A3.3. <i>Rhox3-ps </i>(white arrow) has a stop codon in the homeobox.</div>
</figcaption>
</figure>
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data-image-alt="Figure 6"
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data-figure-id="F6">
<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/87c8bd82d86d/1471-2148-11-169-6.gif"
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<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><b> Origin of the <i> LEUTX </i> gene… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><b> Origin of the <i> LEUTX </i> gene in the human genome </b> . The <i> LEUTX </i> homeobox…</div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6
</strong>
<div class="figure-caption-contents"><b>Origin of the <i>LEUTX </i>gene in the human genome</b>. The <i>LEUTX </i>homeobox gene (orange arrow) plus four unusual non-homeobox genes (light grey arrows) form a linked set of genes in the human genome (dashed box). These genes are not present at the syntenic location in mouse, rat, cow or dog genomes.</div>
</figcaption>
</figure>
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data-figure-id="F7">
<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/168d3044b9d0/1471-2148-11-169-7.gif"
alt="Figure 7" />
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<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><b> The mouse Obox loci and… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><b> The mouse Obox loci and associated genes </b> . There are 36 mouse Obox…</div>
</div>
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 7
</strong>
<div class="figure-caption-contents"><b>The mouse Obox loci and associated genes</b>. There are 36 mouse Obox homeobox loci, comprising 6 intron-containing genes (orange arrows) and 28 intronless loci (unfilled arrows) on chromosome 7, plus intronless probable pseudogenes on chromosome 17. Four other homeobox genes, not clearly part of the Obox family, are linked to the large Obox cluster: <i>Crxos1, Gm5585 </i>and <i>Gm7235 </i>and <i>Crx </i>(red arrows).</div>
</figcaption>
</figure>
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data-figure-id="F8">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-7"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/583be2aceff3/1471-2148-11-169-8.gif"
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<strong class="figure-label">
<p> Figure 8 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> MSX3 </i> gene has been… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 8 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> MSX3 </i> gene has been lost in human and dog genomes </b> . The…</div>
</div>
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 8
</strong>
<div class="figure-caption-contents"><b>The <i>MSX3 </i>gene has been lost in human and dog genomes</b>. The <i>Msx3 </i>gene is located in syntenic regions of mouse, rat and pig genomes (orange arrows), but absent at the equivalent location in human and pig. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
</figcaption>
</figure>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/387ef2586aac/1471-2148-11-169-9.gif"
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<strong class="figure-label">
<p> Figure 9 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> Ventx </i> gene has been… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 9 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> Ventx </i> gene has been lost in rodent genomes </b> . The <i> VENTX </i> gene…</div>
</div>
<figcaption id="figure-caption-8" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 9
</strong>
<div class="figure-caption-contents"><b>The <i>Ventx </i>gene has been lost in rodent genomes</b>. The <i>VENTX </i>gene is located in syntenic regions of human, rat, dog and chicken genomes (orange arrows), but absent at the equivalent location in mouse and rat. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
</figcaption>
</figure>
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<strong class="figure-label">
<p> Figure 10 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> ARGFX </i> locus has been… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 10 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> ARGFX </i> locus has been lost in rodent genomes </b> . The <i> ARGFX </i> gene…</div>
</div>
<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 10
</strong>
<div class="figure-caption-contents"><b>The <i>ARGFX </i>locus has been lost in rodent genomes</b>. The <i>ARGFX </i>gene is located in syntenic regions of human and cow (orange arrows), but absent at the equivalent location in mouse and rat. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
</figcaption>
</figure>
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<strong class="figure-label">
<p> Figure 11 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> DPRX </i> gene has been… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 11 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> DPRX </i> gene has been lost in rodent genomes </b> . The <i> DPRX </i> gene…</div>
</div>
<figcaption id="figure-caption-10" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 11
</strong>
<div class="figure-caption-contents"><b>The <i>DPRX </i>gene has been lost in rodent genomes</b>. The <i>DPRX </i>gene is located in syntenic regions of human, dog and horse (orange arrows), but absent at the equivalent location in mouse and rat. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
</figcaption>
</figure>
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alt="Figure 12" />
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<p> Figure 12 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> SHOX </i> gene has been… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 12 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> SHOX </i> gene has been lost in rodent genomes </b> . The <i> SHOX </i> gene…</div>
</div>
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<strong class="figure-label">
Figure 12
</strong>
<div class="figure-caption-contents"><b>The <i>SHOX </i>gene has been lost in rodent genomes</b>. The <i>SHOX </i>gene is located in syntenic regions of human (X and Y chromosomes) and chicken (orange arrows), but absent at the equivalent location in mouse and rat. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
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<p> Figure 13 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> RAX2 </i> gene has been… </b></div>
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</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 13 </p>
</strong>
<div class="figure-caption-contents"><b> The <i> RAX2 </i> gene has been lost in rodent genomes </b> . The <i> RAX2 </i> gene…</div>
</div>
<figcaption id="figure-caption-12" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 13
</strong>
<div class="figure-caption-contents"><b>The <i>RAX2 </i>gene has been lost in rodent genomes</b>. The <i>RAX2 </i>gene is located in syntenic regions of human and chicken (orange arrows), but absent at the equivalent location in mouse and rat. Non-homeobox genes used as indicators of chromosomal synteny are shown as grey arrows.</div>
</figcaption>
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<strong class="figure-label">
<p> Figure 14 </p>
</strong>
<div class="figure-caption-contents"><b> Tprx loci are not present… </b></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
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<p> Figure 14 </p>
</strong>
<div class="figure-caption-contents"><b> Tprx loci are not present in rodent genomes </b> . In the human genome,…</div>
</div>
<figcaption id="figure-caption-13" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 14
</strong>
<div class="figure-caption-contents"><b>Tprx loci are not present in rodent genomes</b>. In the human genome, the Tprx family contains one probable functional gene (<i>TPRX1</i>) and a possibly non-functional tandem duplicate (<i>TPRX2P</i>) at chromosome 19q13, either side of the Otx-family <i>CRX </i>gene. The additional Tprx loci, <i>TPRX1P1, TPRX1P2 </i>and <i>TPRXL, </i>are elsewhere in the genome and are not shown. Examination of the region syntenic to human 19q13 in other mammals reveals clear orthologues of Tprx family loci in cow and dog, but not mouse and rat. In rodents, another homeobox gene <i>Crxos1 </i>is found. Orange arrows indicate homeobox genes; grey arrows are non-homeobox genes.</div>
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data-figure-id="F15">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-14"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c9/3141429/e45bb87d45f4/1471-2148-11-169-15.gif"
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<p> Figure 15 </p>
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<div class="figure-caption-contents"><b> A summary of homeobox gene… </b></div>
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<p> Figure 15 </p>
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<div class="figure-caption-contents"><b> A summary of homeobox gene dynamics in the mouse and human evolutionary lineages… </b></div>
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Figure 15
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<div class="figure-caption-contents"><b>A summary of homeobox gene dynamics in the mouse and human evolutionary lineages</b>. The majority of homeobox genes are conserved between mouse and human lineages (grey squares), although some have undergone duplication to different extents (cascaded boxes). Humans have lost the <i>Msx3 </i>gene; mice have lost <i>VENTX, ARGFX, DPRX, SHOX, RAX2, LOC647589, NANOGB </i>and <i>TPRX1 </i>(dashed boxes). Three new homeobox loci (<i>Gm7235, Gm5585 </i>and <i>Crxos1</i>) and one new cluster (Obox) arose in the rodent lineage; one new gene <i>Leutx </i>arose in the lineage leading to primates.</div>
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Larroux C, Fahey B, Degnan SM, Adamski M, Rokhsar DS, Degnan BM. The NK homeobox gene cluster predates the origin of Hox genes. Curr Biol. 2007;17(8):706710. doi: 10.1016/j.cub.2007.03.008.
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Holland PWH, Booth HAF, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol. 2007;5:47. doi: 10.1186/1741-7007-5-47.
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Ryan JF, Burton PM, Mazza ME, Kwong GK, Mullikin JC, Finnerty JR. The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis. Genome Biol. 2006;7(7):R64. doi: 10.1186/gb-2006-7-7-r64.
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Edvardsen RB, Seo HC, Jensen MF, Mialon A, Mikhaleva J, Bjordal M, Cartry J, Reinhardt R, Weissenbach J, Wincker P. et al.Remodelling of the homeobox gene complement in the tunicate Oikopleura dioica. Curr Biol. 2005;15(1):R1213. doi: 10.1016/j.cub.2004.12.010.
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