Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Abstract

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1Lieberman D.E. McBratney B.M. Krovitz G. The evolution and development of cranial form in Homo sapiens.Proc. Natl. Acad. Sci. USA. 2002; 99: 1134-1139Crossref PubMed Scopus (324) Google Scholar, 2Bruner E. Manzi G. Arsuaga J.L. Encephalization and allometric trajectories in the genus Homo: evidence from the Neandertal and modern lineages.Proc. Natl. Acad. Sci. USA. 2003; 100: 15335-15340Crossref PubMed Scopus (229) Google Scholar, 3Bruner E. Geometric morphometrics and paleoneurology: brain shape evolution in the genus Homo.J. Hum. Evol. 2004; 47: 279-303Crossref PubMed Scopus (203) Google Scholar, 4Neubauer S. Hublin J.J. Gunz P. The evolution of modern human brain shape.Sci. Adv. 2018; 4: eaao5961Crossref PubMed Scopus (156) Google Scholar]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4Neubauer S. Hublin J.J. Gunz P. The evolution of modern human brain shape.Sci. Adv. 2018; 4: eaao5961Crossref PubMed Scopus (156) Google Scholar, 5Kochiyama T. Ogihara N. Tanabe H.C. Kondo O. Amano H. Hasegawa K. Suzuki H. Ponce de León M.S. Zollikofer C.P.E. Bastir M. et al.Reconstructing the Neanderthal brain using computational anatomy.Sci. Rep. 2018; 8: 6296Crossref PubMed Scopus (48) Google Scholar]. 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 [6Green R.E. Krause J. Briggs A.W. Maricic T. Stenzel U. Kircher M. Patterson N. Li H. Zhai W. Fritz M.H. et al.A draft sequence of the Neandertal genome.Science. 2010; 328: 710-722Crossref PubMed Scopus (2469) Google Scholar, 7Prüfer K. de Filippo C. Grote S. Mafessoni F. Korlević P. Hajdinjak M. Vernot B. Skov L. Hsieh P. Peyrégne S. et al.A high-coverage Neandertal genome from Vindija Cave in Croatia.Science. 2017; 358: 655-658Crossref PubMed Scopus (275) Google Scholar]. 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.