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. 2019 Jan 7;29(1):120-127.e5.
doi: 10.1016/j.cub.2018.10.065. Epub 2018 Dec 13.

Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Philipp Gunz  1 , Amanda K Tilot  2 , Katharina Wittfeld  3 , Alexander Teumer  4 , Chin Yang Shapland  2 , Theo G M van Erp  5 , Michael Dannemann  6 , Benjamin Vernot  6 , Simon Neubauer  7 , Tulio Guadalupe  2 , Guillén Fernández  8 , Han G Brunner  9 , Wolfgang Enard  10 , James Fallon  11 , Norbert Hosten  12 , Uwe Völker  13 , Antonio Profico  14 , Fabio Di Vincenzo  15 , Giorgio Manzi  14 , Janet Kelso  6 , Beate St Pourcain  16 , Jean-Jacques Hublin  7 , Barbara Franke  17 , Svante Pääbo  6 , Fabio Macciardi  18 , Hans J Grabe  19 , Simon E Fisher  20
Affiliations

Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Philipp Gunz et al. Curr Biol. .

Erratum in

  • Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity.
    Gunz P, Tilot AK, Wittfeld K, Teumer A, Shapland CY, van Erp TGM, Dannemann M, Vernot B, Neubauer S, Guadalupe T, Fernández G, Brunner HG, Enard W, Fallon J, Hosten N, Völker U, Profico A, Di Vincenzo F, Manzi G, Kelso J, St Pourcain B, Hublin JJ, Franke B, Pääbo S, Macciardi F, Grabe HJ, Fisher SE. Gunz P, et al. Curr Biol. 2019 Mar 4;29(5):895. doi: 10.1016/j.cub.2019.02.008. Curr Biol. 2019. PMID: 30836076 Free PMC article. No abstract available.

Abstract

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.

Keywords: Neandertal; basal ganglia; brain shape; cerebellum; evolution; gene expression; genetic association; homo sapiens; magnetic resonance imaging; myelination.

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Conflict of interest statement

DECLARATION OF INTERESTS

Authors declare no competing interests. B.F. received educational speaking fees from Shire and Medice.

Figures

Figure 1.
Figure 1.. Endocranial Shape Differences between Neandertals and Modern Humans
(A) CT scan of the Neandertal fossil from La Chapelle-aux-Saints with a typical elongated endocranial imprint (red). (B) CT scan of a modern human showing the characteristic globular endocranial shape (blue). Arrows highlight the enlarged posterior cranial fossa (housing the cerebellum) as well as bulging of parietal bones in modern humans compared to Neandertals. (C) Average endocranial shape of adult Neandertals; each vertex of the surface corresponds to a semilandmark. (D) Average endocranial shape of modern humans. Areas shaded in green are relatively larger in modern humans than in Neandertals. (E and F) The semilandmarks used to quantify overall endocranial shape from MRI scans of living people shown on the MNI 152 template in lateral and frontal views, respectively.
Figure 2.
Figure 2.. Globularity Scores of CT and MRI Scans
(A) Principal component analysis of endocranial shape. 99% confidence ellipses are shown for modern human CT scans from Europe (blue; n = 19), MRI scans of present-day humans (yellow; n = 6,575), and Neandertal CT scans (red; n = 7); two Homo heidelbergensis individuals are plotted in black. (B) Frequency plot of globularity scores computed for data shown in (A). This globularity score quantifies overall endocranial shape by projecting each individual onto the vector between the elongated average shape of Neandertals and the globular average shape of present-day humans. Inset shows example MRI scans associated with low (left) and high (right) globularity scores among present-day humans. See also Figure S1.
Figure 3.
Figure 3.. Endocranial Globularity in Modern Humans Is Associated with Introgressed Neandertal Haplotypes
(A) Association statistics for introgressed Neandertal SNPs (solid line, significance, adjusted for multiple testing; dashed line, suggestive significance). (B) Quantile-quantile plot of association p values, showing the expected uniform distribution, with the outliers representing significant associations. (C) Forest plots depict the effects of the top Neandertal SNPs, for each study and genotyping batch. Boxes are proportional to weight, with whiskers representing the 95% confidence interval; diamonds represent a linear mixed-effect model incorporating all five datasets. (D) Covariate-corrected globularity scores by genotype. All data points are shown; boxes represent 25th and 75th percentiles; whiskers represent 1.5 times the interquartile range.
Figure 4.
Figure 4.. Introgressed Neandertal Fragments Associated with Globularity
(A and C) Detailed views of the kilobase surrounding the Neandertal SNPs within the introgressed haplotypes (brown bars) on chromosomes 1 (A) and 18 (C). (B and D) Expression quantitative trait loci data from the GTEx resource, showing the impact of Neandertal alleles on gene expression for UBR4 (B) and PHLPP1 (D), as defined by [24]. See also Figures S3 and S4.
See this image and copyright information in PMC

Comment in

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