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Association between changes in lipid catabolism and increased gene flow from Neanderthals to Europeans Ekaterina E. Khrameeva, Mikhail S. Gelfand
Institute for Information Transmission Problems, RAS, Bolshoy Karetny per. 19, Moscow, 127994, Russia, khrameeva@genebee.msu.ru

Philipp Khaitovich
CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, China, khaitovich@eva.mpg.de

Neanderthals and modern humans diverged fro m the same ancestral species approximately 800 to 400 thousand years ago . After the species' separat ion, Neanderthals left African continent and co lonized Europe, Central Asia and might have spread far into the Asia n continent. Modern humans spread quickly throughout all cont inents and co-existed wit h Neanderthals in Europe and Asia unt il Neanderthal extinction. While Neanderthals are ext inct, fragments of their geno me might still persist in th e geno mes of contemporary humans living outside of Africa. Our study shows that although Neanderthal-like geno mic regions averagely occupy the same percentage in all out -of-Africa human individuals, their distribut ion varies amo ng human populat ions. Specifically, contemporary humans of European decent show greater concentration of Neanderthal-like sequences in specific functional categories. Genes invo lved in lipid catabo lism contain large excess Neanderthal-like sequences in Europeans (gene flow estimate: 24.3%), but not in Asians (12.4%), while both values were greater than the geno me average (6%). We speculate that genetic changes that evolved on the Neanderthal evo lut ionary l ineage gave ancestors of modern Europeans a certain select ive advantage, possibly due to shared environmenta l condit ions. While lipid catabo lism cannot be assayed in Neanderthals, we took advantage of genet ic divergence between human populat ions, chimpanzees and Neanderthals to predict metabo lic divergence expected from the observed excess of Neanderthal gene flow. We confirmed predicted changes in lipid catabo lism using hydrophobic metabo lo me measurements in the


human and chimpanzee brains and further linked these metabo lic changes to gene expressio n divergence. Further studies investigating Neanderthal gene flow distribut ion in contemporary human populations are needed to test this hypothesis and elucidate its funct ional implicat ions. We thank Micha el Lachmann for helpful discussio ns and suggest ions ; Kasia Bozek a nd Liu He
for assistance with the data preparation and pre-processing. The study was supported by

Chinese Academy o f Sciences (Fellowship for Young International Scient ists) and Russian Foundat ion of Basic Research (grant 12-04-31789).