Genomic analysis of a novel Neanderthal from Mezmaiskaya Cave provides insights into the genetic relationships of Middle Palaeolithic populations

Abstract

The Mezmaiskaya cave is located on the North Caucasus near the border that divides Europe and Asia. Previously, fossil remains for two Neanderthals were reported from Mezmaiskaya Cave. A tooth from the third archaic hominin specimen (Mezmaiskaya 3) was retrieved from layer 3 in Mezmaiskaya Cave. We performed genome sequencing of Mezmaiskaya 3. Analysis of partial nuclear genome sequence revealed that it belongs to a Homo sapiens neanderthalensis female. Based on a high-coverage mitochondrial genome sequence, we demonstrated that the relationships of Mezmaiskaya 3 to Mezmaiskaya 1 and Stajnia S5000 individuals were closer than those to other Neanderthals. Our data demonstrate the close genetic connections between the early Middle Palaeolithic Neanderthals that were replaced by genetically distant later group in the same geographic areas. Based on mitochondrial DNA (mtDNA) data, we suggest that Mezmaiskaya 3 was the latest Neanderthal individual from the early Neanderthal’s branches. We proposed a hierarchical nomenclature for the mtDNA haplogroups of Neanderthals. In addition, we retrieved ancestral mtDNA mutations in presumably functional sites fixed in the Neanderthal clades, and also provided the first data showing mtDNA heteroplasmy in Neanderthal specimen.

Archaeological evidence for two culture diverse Neanderthal populations in the North Caucasus and contacts between them

“…This archaeological data are supported by the results of palaeogenetic analyses of there Neanderthal specimens from Mezmaiskaya cave [ 23 , 27 , 28 ]. They indicate that the Eastern Micoquian Neanderthals from the north-western Caucasus belong to European Neanderthals and represent a group of Neandertals that diverged from other European Neanderthals after about 110 ka [ 23 ] or approximately between 100–80 ka [ 27 ].…”

“…This archaeological data are supported by the results of palaeogenetic analyses of there Neanderthal specimens from Mezmaiskaya cave [23,27,28]. They indicate that the Eastern Micoquian Neanderthals from the north-western Caucasus belong to European Neanderthals…”

“…They indicate that the Eastern Micoquian Neanderthals from the north-western Caucasus belong to European Neanderthals and represent a group of Neandertals that diverged from other European Neanderthals after about 110 ka [ 23 ] or approximately between 100–80 ka [ 27 ]. The palaeogenetic research also shows a great similarity between mtDNA genomes of three Neanderthals from geographically distant Eastern Micoquian contexts dated from late MIS 5—Stajnia S5000 from Stajnia cave (Poland), and Mezmaiskaya 1 and Mezmaiskaya 3—and they all fall beyond the mtDNA variation of the late European Neanderthals [ 28 , 41 ]. Also, studies of Neandertal genomes from Mezmaiskaya indicate that there was a population turnover in the Eastern Micoquian Neandertal population of the north-western Caucasus during early MIS 3, most likely as the result of a population related to western European Neanderthals replacing earlier Eastern Micoquian Neanderthals in the region [ 27 , 28 ].…”

“…Fossil remains of three Neanderthal individuals have been found in two MP layers at Mezmaiskaya cave, in the top MP layer 2 (Mezmaiskaya 2) and in the lowermost MP layer 3 (Mezmaiskaya 1 and Mezmaiskaya 3), and detailed morphometric and palaeogenetic analyses have been performed for all individuals [23][24][25][26][27][28] (Data 3 in S1 Text). The ages obtained using branch shortening for Mezmaiskaya 1 and Mezmaiskaya 3 individuals are older than ESR estimates for layer 3, and indicate that these Neanderthals, representing the early Eastern Micoquian population in the north-western Caucasus, lived approximately 100-70 ka in MIS 5 [27,28].…”

“…Fossil remains of three Neanderthal individuals have been found in two MP layers at Mezmaiskaya cave, in the top MP layer 2 (Mezmaiskaya 2) and in the lowermost MP layer 3 (Mezmaiskaya 1 and Mezmaiskaya 3), and detailed morphometric and palaeogenetic analyses have been performed for all individuals [23][24][25][26][27][28] (Data 3 in S1 Text). The ages obtained using branch shortening for Mezmaiskaya 1 and Mezmaiskaya 3 individuals are older than ESR estimates for layer 3, and indicate that these Neanderthals, representing the early Eastern Micoquian population in the north-western Caucasus, lived approximately 100-70 ka in MIS 5 [27,28]. This older age estimate for layer 3 well agrees with the palaeogeographic and archaeological data from Mezmaiskaya and comparative data from other sites, indicating that the early stage of the Eastern Micoquian Neanderthal occupation of the north-western Caucasus corresponds to the interval from late MIS 5 through the end of MIS 4 [12].…”