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<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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj">
<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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj">
<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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj">
<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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj">
<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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj">
<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="35816093">
<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://doi.org/10.7554/eLife.75464"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=8981&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=35816093&amp;db=pubmed&amp;nlmid=101579614"
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eLife Sciences Publications, Ltd
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/35816093/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=35816093&amp;db=pubmed&amp;nlmid=101579614"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
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Free PMC article
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<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="/35816093/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/35816093/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="35816093" 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%2F35816093%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="LX1SDlMKJxibZXh1yOCa34UtMAPGLfNZ2KLXgbf6j85FTonRb7fcxcq7kExSEQlj"><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"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
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..."
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The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals
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Proteins associated with the spindle apparatus, a cytoskeletal structure that ensures the proper segregation of chromosomes during cell division, experienced an unusual number of amino acid substitutions in modern humans after the split from the ancestors of Neandertals and Denisovans. Here, we analyze the history of these substitutions and show that some of the genes in which they occur may have been targets of positive selection. We also find that the two changes in the kinetochore scaffold 1 (KNL1) protein, previously believed to be specific to modern humans, were present in some Neandertals. We show that the <i>KNL1</i> gene of these Neandertals shared a common ancestor with present-day Africans about 200,000 years ago due to gene flow from the ancestors (or relatives) of modern humans into Neandertals. Subsequently, some non-Africans inherited this modern human-like gene variant from Neandertals, but none inherited the ancestral gene variants. These results add to the growing evidence of early contacts between modern humans and archaic groups in Eurasia and illustrate the intricate relationships among these groups.
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evolutionary biology; gene flow; genetics; genomics; human; human evolution; neandertals; positive selection; spindle.
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<p> Figure 1.. Genomic regions around spindle genes… </p>
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<strong class="figure-label">
<p> Figure 1.. Genomic regions around spindle genes where archaic humans fall outside the modern human… </p>
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<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.. Genomic regions around spindle genes where archaic humans fall outside the modern human variation.
</strong>
<div class="figure-caption-contents">Each panel corresponds to the region around the missense change(s) (red stars) in a spindle gene. The grey boxes correspond to exons. The curves give the posterior probability (computed as in Peyrégne et al., 2017) that an archaic genome (<i>Altai Neandertal</i> in red, <i>Denisova 3</i> in orange) is an outgroup to present-day African genomes at a particular position (dots on the curves correspond to informative positions, that is polymorphic positions or fixed derived substitutions in Africans from the 1,000 Genomes Project phase III, compared to four ape genomes). Chromosomal locations are given on top.</div>
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<p> Figure 1—figure supplement 1.. Genomic regions where… </p>
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<strong class="figure-label">
<p> Figure 1—figure supplement 1.. Genomic regions where archaic humans fall outside the modern human variation,… </p>
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Figure 1—figure supplement 1.. Genomic regions where archaic humans fall outside the modern human variation, identified using the most recent deCODE recombination map (Halldorsson et al., 2019).
</strong>
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<p> Figure 2.. Evidence for selection in the… </p>
</strong>
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</div>
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<strong class="figure-label">
<p> Figure 2.. Evidence for selection in the spindle genes with age estimates of these substitutions. </p>
</strong>
</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 2.. Evidence for selection in the spindle genes with age estimates of these substitutions.
</strong>
<div class="figure-caption-contents">(<b>A</b>) The genetic length of segments around the missense substitutions where the Altai Neandertal and Denisova 3 fall outside the human variation (Figure 1) using the African-American map, AAmap, or the deCODE map, deCODE19. The grey histogram corresponds to the length distribution of such segments in neutral simulations (Peyrégne et al., 2017). Candidate genes for selection (red) are those with segments longer than 0.025cM (Peyrégne et al., 2017) (vertical red dashed line). (<b>B</b>) Cumulative distributions of pairwise times to the most recent common ancestors (TMRCA) among present-day African chromosomes with the most distant relationships (red; see Methods), or between the chromosomes of present-day Africans and either present-day individuals with the ancestral versions of the missense substitutions (Modern (anc), in black) or archaic humans (other colors). The pink areas correspond to estimated time intervals for the origin of the missense substitutions and their bounds correspond to the average TMRCAs over the red curve and the next one (back in time), respectively. (<b>C</b>) Summary of ages of substitutions as described in panel B. Genes with evidence of positive selection are highlighted in red.</div>
</figcaption>
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itemprop="contentUrl"
aria-describedby="figure-caption-3"
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data-image-width="772"
data-image-height="323"
data-image-alt="Figure 3."
data-pmc-id="PMC9273211"
data-figure-id="fig3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbad/9273211/e50d3e50004b/elife-75464-fig3.gif"
alt="Figure 3." />
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<strong class="figure-label">
<p> Figure 3.. A modern human-like haplotype in… </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3.. A modern human-like haplotype in some Neandertals. </p>
</strong>
<div class="figure-caption-contents"><p> Genotypes from 13 archaic individuals (y-axis)… </p></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 3.. A modern human-like haplotype in some Neandertals.
</strong>
<div class="figure-caption-contents">Genotypes from 13 archaic individuals (y-axis) are shown in a region around the two missense changes (dots) in <i>KNL1</i>. We only show positions (x-axis) that are derived in all Luhya and Yoruba individuals from the 1,000 Genomes Project compared to four great apes (Peyrégne et al., 2017) and at least one high-coverage archaic genome (<i>Chagyrskaya 8</i>, <i>Denisova 3</i>, <i>Vindija 33.19</i> and <i>Altai Neandertal</i>, i.e., <i>Denisova 5</i>). The colors of the squares and dots represent the genotype, with ancestral and derived alleles. For the low coverage archaic genomes, we randomly sampled a sequence at each position. Red lines indicate the modern human-like haplotype.</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="742"
data-image-height="436"
data-image-alt="Figure 4."
data-pmc-id="PMC9273211"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
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alt="Figure 4." />
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<strong class="figure-label">
<p> Figure 4.. The modern human-like KNL1 haplotype… </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4.. The modern human-like KNL1 haplotype in Neandertals. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Pairwise differences between… </p></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 4.. The modern human-like KNL1 haplotype in Neandertals.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Pairwise differences between two high coverage Neandertal genomes (<i>Chagyrskaya 8</i> and <i>Altai Neandertal</i> (<i>Denisova 5</i>)) in non-overlapping sliding windows of 276 kb (histogram) and in the <i>KNL1</i> region (vertical cyan line; chr15:40,818,03541,094,166, hg19). Windows with less than 10,000 genotype calls for both Neandertals were discarded. (<b>B</b>) The expected length distributions under a model of incomplete lineage sorting based on local recombination rate estimates from the African-American (AA) and deCODE recombination maps and the length of the modern human-like <i>KNL1</i> haplotype in Neandertals (vertical cyan line). (<b>C</b>) Left panel: Time to the most recent common ancestor (TMRCA) between the <i>Chagyrskaya 8</i> Neandertal (who carries the modern human-like haplotype) and <i>KNL1</i> haplotypes in present-day humans with their 95% confidence intervals (bars) for chr15:40,885,10740,963,160 (hg19). The size of the points corresponds to the number of chromosomes carrying this haplotype in the HGDP dataset. The black rectangles highlight subsets of haplotypes with TMRCAs more recent than the modern-archaic population split time (Prüfer et al., 2017) (shaded pink area). Right panel: Distribution of pairwise TMRCAs between the Neandertal and present-day humans from the HGDP dataset in the region of <i>KNL1</i> and two other regions with archaic haplotypes in present-day humans (Controls, Zeberg and Pääbo, 2020; Dannemann et al., 2016; COVID risk region: chr3:45,859,65145,909,024; <i>TLR6, 1 &amp; 10</i>: chr4:38,760,33838,846,385). We used the <i>Vindija 33.19</i> genome for the COVID risk haplotype and the <i>Chagyrskaya 8</i> genome otherwise.</div>
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<strong class="figure-label">
<p> Figure 4—figure supplement 1.. Genotypes of the… </p>
</strong>
</div>
</div>
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<strong class="figure-label">
<p> Figure 4—figure supplement 1.. Genotypes of the 12 non-African individuals that inherited one copy of… </p>
</strong>
</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 4—figure supplement 1.. Genotypes of the 12 non-African individuals that inherited one copy of <i>KNL1</i> from archaic humans.
</strong>
<div class="figure-caption-contents">We show positions within 40kb downstream of the modern-like <i>KNL1</i> haplotype identified in <i>Chagyrskaya 8</i> to highlight 7 positions (red marks) where only those 12 individuals (out of 929 individuals across worldwide populations Bergström et al., 2020) carry a derived allele seen in at least one Neandertal genome. We only show positions where at least one of the 12 individuals is heterozygous. The upper panel (Archaics) shows the alleles carried by high-coverage archaic human genomes without the modern-like <i>KNL1</i> haplotype. The middle panel (<i>Chagyrskaya 8</i>-like) shows the alleles carried by four Neandertal genomes with the modern-human like <i>KNL1</i> haplotype and the 12 present-day non-African genomes that inherited one copy of <i>KNL1</i> from archaic humans. The lower panel (Other haplotypes) shows the alleles carried by the other chromosomes (that did not inherit a copy ok <i>KNL1</i> from archaic humans) of these 12 individuals. For the archaic human genomes, one allele was sampled randomly at heterozygous positions.</div>
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<p> Figure 5.. Schematic illustration of the history… </p>
</strong>
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<p> Figure 5.. Schematic illustration of the history of KNL1. </p>
</strong>
<div class="figure-caption-contents"><p> The tree delineated in black corresponds… </p></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 5.. Schematic illustration of the history of KNL1.
</strong>
<div class="figure-caption-contents">The tree delineated in black corresponds to the average relationship between the modern and archaic human populations. The inner colored trees correspond to the relationship of different <i>KNL1</i> lineages, with arrows highlighting the direction of gene flow between populations. The corresponding haplotypes are illustrated on the sides of the tree and show the recombination history in the region (e.g. the recombinant Neandertal haplotype with variants of putative archaic origin in non-Africans). Dots correspond to informative positions, and the stars illustrate the missense substitutions. The age of relevant ancestors are marked by horizontal dotted lines. MH: Modern human.</div>
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