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Short Report
The Cognitive Ability of Extinct Hominins: Bringing Down the Hierarchy Using
Genomic Evidences
repeated exposure to a visual cue. Remarkably, 95% of the
Neandertal positions retrieved have the same allele found
in sap...
Mundy (2012) suggested that positive selection in genes
linked to human microcephaly was associated with the
evolution of ...
specimen: new insights on their evolutionary histories using whole-
genome comparisons. Genet Mol Biol 35:904–911.
Reich D...
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PAIXÃO-CORTES et al [2013] - The cognitive ability of extinct hominis


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PAIXÃO-CORTES et al [2013] - The cognitive ability of extinct hominis

  1. 1. Short Report The Cognitive Ability of Extinct Hominins: Bringing Down the Hierarchy Using Genomic Evidences VANESSA R. PAIX~AO-C^ORTES,1 LUCAS HENRIQUES VISCARDI,1,2 FRANCISCO MAURO SALZANO,1 MARIA CATIRA BORTOLINI,1 AND TABITA H €UNEMEIER1 * 1 Departamento de Genetica, Instituto de Bioci^encias, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil 2 Laboratorio de Ensino e Pesquisa em Antropologia e Arqueologia, Instituto de Ci^encias Humanas e da Informac¸~ao, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil Background: The availability of the full genomes of Homo sapiens, Homo neanderthalensis, and Denisovans, as well as modern bioinformatic tools, are opening new possibilities for the understanding of the differences and similar- ities present in these taxa. Methods: We searched for cognitive genes, examined their status in the genomes of these three entities. All substitu- tions present among them were retrieved. Results: We found 93 nonsynonymous substitutions in 51 cognitive genes, in which the derived allele was present in archaic and modern humans and the ancestral allele in other nonhuman primates. Conclusions: The general picture obtained is of similarity in cognitive genes between extinct and extant humans. Am. J. Hum. Biol. 25:702–705, 2013. VC 2013 Wiley Periodicals, Inc. Despite sharing most of their genetic background, humans are remarkably different from other great apes (Noonan, 2010). The most striking differences are the cog- nitive skills acquired by Homo sapiens, and the fact that the knowledge had been accumulated and refined throughout its evolution as a species (Varki and Altheide, 2005). Within the genus Homo these differences may not be as striking. Homo sapiens, Neandertals, and Deniso- vans coexisted, probably interacting with each other in the same ecological niche (Mellars, 2004; Noonan, 2010; Reich et al., 2010). Many assumptions have been made about the reasons for the replacement of archaic by mod- ern humans in Eurasia, many of them related to the cognitive differences among them. Some of these assump- tions are based on archeological record, pointing to a lower sophistication in the cultural traits of the archaic humans (Henshilwood, and Marean, 2003; Mellars, 2004). Recently, with the publication of the genomes of these two extinct Homo species (Neandertal, Green et al., 2010; Denisovans, Reich et al., 2010) new discoveries have con- tributed to a better understanding of the level of cognitive development of Neandertals (for instance, speech ability, Krause et al., 2007). In this study we investigated the variability in 162 cog- nition genes present in the genomes of these three Homo species, in an attempt to verify the variants that may have played an important role in cognitive abilities development. MATERIALS AND METHODS Genes directly related to cognitive ability were searched using AmiGO database (GO:0050890; cognition: http:// Gene details were obtained from GeneCards (http://www.gene- All nonsynonymous changes in these genes which were different in modern humans and chimpanzees were retrieved in the gorilla, orangutan, Rhesus, marmo- set, tarsier, mouse lemur, and bushbaby, as well as in the Neandertal and Denisova specimen genomes using the USCS browser ( org5human). We considered the allele as ancestral every time it was present in chimpanzee and in other nonhu- man primates, while a derived allele is that present only in Homo. Any allele could only be considered as exclusive if it was present in only one of the primates studied. Nucleotide differences considering theses 162 genes, as well as in other relevant regions (e.g enhancer) were checked using the track “variant calls from high-coverage genome sequence of an archaic Denisovan individual (hg19)” and “Neandertal Assembly and Analysis (hg18)”. The Grantham score (Grantham, 1974) was then used to categorize all the corresponding amino acid changes into classes of chemical similarity. They were classified as con- servative (0–50), moderately conservative (51–100), mod- erately radical (101–150), or radical (150). RESULTS AND DISCUSSION The ontology search allowed the selection of 162 genes related to cognitive processes. We found 93 non- synonymous substitutions in 51 cognitive genes, in which the derived allele was present in humans (archaic and/or modern) and the ancestral allele in nonhuman primates (Table 1). It is noteworthy that the TANC1 gene has 8 nonsynonymous changes (Fig. 1). This gene is associated to visual learning, referring to any process in an organism in which a change in behavior occurs in response to Additional Supporting Information may be found in the online version of this article. Contract grant sponsor: Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq), Fundac¸~ao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Programa de Apoio a Nucleos de Excel^encia (PRONEX). The first two authors contributed equally to this work. *Correspondence to: Tabita H€unemeier, Programa de Pos-Graduac¸~ao em Genetica e Biologia Molecular, Departamento de Genetica, Instituto de Bioci^encias, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil. E-mail: Received 6 February 2013; Revision received 3 June 2013; Accepted 11 June 2013 DOI: 10.1002/ajhb.22426 Published online 1 August 2013 in Wiley Online Library ( VC 2013 Wiley Periodicals, Inc. AMERICAN JOURNAL OF HUMAN BIOLOGY 25:702–705 (2013)
  2. 2. repeated exposure to a visual cue. Remarkably, 95% of the Neandertal positions retrieved have the same allele found in sapiens, in 2% the locus was in heterozygosis for ances- tral and derived alleles, and 3% showed new variants. In the Denisova specimen just two positions were recovered with an ancestral allele and one locus in heterozygosis. From the 93 substitutions, 49% were classified as conserv- ative, 38% as moderately conservative, 12% as moderately radical, and 1 as radical (Supporting Information Table S1). Thirty three of the 93 (35%) were not fixed in Nean- dertal or H. sapiens and the additional alleles found in our species besides those listed in Supporting Information Table S1 occur in all continents (Supporting Information Table S2). According to Green et al. (2010), some genes associated with diseases that affect cognitive capacities present the derived alleles in modern human noncoding regions. The authors hypothesized that these genes involved in cogni- tive development were positively selected during the early history of anatomically modern humans. Meyer et al. (2012) suggested that Denisovans had dif- ferent cognitive abilities from extant humans based on unique modern human nonsynonymous changes found in nine genes associated with brain function or nervous sys- tem development. Our analysis with coding regions point in another direc- tion, since H. sapiens, Neandertals, and Denisova are vir- tually equal when the molecular aspects involved in the cognitive processes considered here are compared. Some recent studies are in accordance with our results. A previ- ous work from our group (Paix~ao-C^ortes et al., 2012) iden- tified four genes involved in neurogenesis and cognition (ASPM, MCPH1, AHI1, and KLK8) that had accelerated evolutionary rates along the lineages leading to Homo since there were no differences between H. sapiens and the extinct humans. Furthermore, Montgomery and TABLE 1. Number of cognition genes, of their non-synonymous substitutions, and their functions as ascertained in the Gene Ontology database N of changes N of genes Gene Gene ontologya 1 27 AAAS, ADNP, CASP1, CHST10, CLN8, DRD3, FABP7, FOXP3, GIP, GLP1R, GRM7, HMGCR, HTR1A, MAOA, MEF2A, MUSK, NGF, OXTR, PAFAH1B1, PPT1, RAB3GAP1, RGS14, SLC24A2, SLC11A2, SRF, STS, TAC1 GO:0007612: learning; GO:0007614: Short-term mem- ory; GO:0007613: Memory; GO:0008306: Associative learning; GO:0008542: Visual Learning; GO:0007611: Learning or memory; GO:0007612: Learning 2 16 APBB1IP, CHRNA4, CYP7B1, CYP8B1, DRD4, FOXP2, GALR2, IL1RN, ITGA8, OXT, PDE1B, PJA2, RASGRF1, SERPINF1, STRA6, VLDLR GO:0008542: Visual learning; GO:0050890: Cognition; GO:0008355: Olfactory learning; GO:0042297: Vocal learning; GO:0007611: Learning or memory; GO:0007613: Memory; GO:0007616: Long-term memory; GO:0007614: Short-term memory 3 3 GRIN2A, SLC6A4, RELN GO:0008542: Visual learning: GO:0007613: Memory; GO:0007611: Learning or memory; GO:0007613: Memory; GO:0007616: Long -term memory; GO:0008306: Associative learning 4 3 CHL1, PDCL, HRH1, GO:0050890: Cognition 5 1 AFF2 GO:0007611: Learning or memory 8 1 TANC1 GO:0008542: Visual learning a At least one of these categories is associated with one of the genes indicated in the previous column. Specific information can be supplied on request. Fig. 1. Phylogenetic tree of four nonhuman and three hominin species considering the 93 nonsynonimous mutations in genes presumably directly related to cognitive ability, as well as the constitution of their different regulatory regions. SRGAP2, SLIT-ROBO RHO GTPase activat- ing protein 2; HARS, human accelerated regions; AUST2, autism susceptibility candidate 2; HACNS1, human accelerated conserved noncoding sequence 1; KLK8, kallikrein-related peptidase 8. ND, No data. [Color figure can be viewed in the online issue, which is available at] GENOME ANALYSIS, EXTANT AND EXTINCT HOMININS 703 American Journal of Human Biology
  3. 3. Mundy (2012) suggested that positive selection in genes linked to human microcephaly was associated with the evolution of primate brain size and suggested that the majority of phenotypic and developmental traits associ- ated with the evolution of the human brain are conserved across primates. Charrier et al. (2012) demonstrated that the SRGAP2 gene passed through two partial duplication processes in the human lineage that led to a difference in its regula- tion by copies that are present in both Homo neandertha- lensis and Homo sapiens. Important implications for cognition, learning, and memory were proposed and enabled them to better understand the ways that led to the Homo encephalization by changes in regulatory processes. Regarding noncoding regions, special attention should be given to the study of Oksenberg et al. (2013). They studied the candidate enhancer sequences of AUTS2 that contains the most significant positively selected genomic regions differentiating sapiens from Neandertals (Green et al., 2010). Six of the enhancers tested in mice were acti- vated in brain development and/or sensorial tissues, and two of them are human accelerated regions (HARs; HAR31, and HACNS369). These authors showed that four of the six enhancers have variants shared by sapiens and neanderthalensis. We found these variants in Denisova (Supporting Information Table S3). Green et al. (2010) already indicated that Neandertals carried the derived state at 91.4% of HARs positions; while Burbano et al. (2012) estimated that at least one archaic hominin allele existed for 84% of all HARs posi- tions. Additionally, H€unemeier et al. (2010), studying changes in a specific HAR (HACNS1; which acts as an enhancer of gene expression influencing important traits such as opposable thumbs, manual dexterity, and bipedal walking) obtained evidence that they were fixed due to positive selection in some period of the hominid evolution- ary history. Supporting Information Table S4 presents data from the seven aforementioned regulatory regions in the three hominin species considered, informing about the sites where they are located, the anatomical regions influ- enced, and the frequencies of the ancestral allele found in the three hominin species. The prevalences observed are similar, with no indication of heterogeneity. Additionally, we investigated all differences between the human reference genome (Hg19), Denisova and 11 modern humans from distinct geographic groups, consid- ering the 162 cognitive genes (Supporting Information Table S5). The number of total differences is similar, but the Denisova present 12,332 exclusive alleles, while the San and Mbuti Pygmy showed 6,461 and 3,692, respec- tively. Other modern humans present a lower number of variants, with a clear gradient from Africa. Excluding the 93 nonsynonymous substitutions, we can assume that the great majority of this variation is represented by synony- mous and intronic variations. Rather than functional implications these results can indicate demographic sce- narios where more ancient populations (Denisova, San, and Pygmy) present a larger number of exclusive alleles and/or relatively large populations. The Denisova data were recently confirmed by preliminary results from other authors ( 6134/799.full). Together, important coding and regulatory changes for specific cognitive traits seem to have predated Homo sapi- ens emergence (Fig. 1). Further analyses must be per- formed to understand how these changes would have influenced the establishment of Homo specific abilities. However, considering our results, if there were cognitive differences related to a loss of competitive ability of extinct humans when compared to anatomic modern humans, these differences left no striking mark in the coding genetic background in the studied genes, suggest- ing that other possibilities, as cultural particularities, can be raised. Our findings are in agreement with new archeo- logical record associated with Neandertal symbolic mate- rial culture. These studies revealed that these hominins might have shared more behavioral traits with modern humans than it used to be believed (Caron et al., 2011; Shipman, 2008; Zilh~ao et al., 2009). LITERATURE CITED Autism Genome Project Consortium. 2010. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466: 368–372. 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