DOI: 10.5061/dryad.sbcc2frk5
title: Natural selection and language genes in humans

description: In this study we construct lists of candidate genes for articulate
 language. Analysis of coding regions of over 100 candidate genes for the
 effects of natural selection (directional episodic selection and
 relaxed/intensified selection) in the various lineages of primates
 (thirty-four nonhuman primate species, plus Homo sapiens Neanderthals and
 Denisovans) revealed a burst of increased selection effects on neural
 genes at the node leading to the Homo sapiens-Neanderthal-Denisova triad,
 followed by bursts of selection effects on neural genes related to
 language in both the Denisovan and Neanderthal lineages. Those latter
 increases in involvement of neural genes in Neanderthals and Denisovans
 can be contrasted with the missing or slight response to selection on
 those same genes in the H. sapiens lineage. The genes involved in these
 bursts can mostly be classified as involved in synapse structure and
 maintenance. We develop a hypothesis for how synaptic efficiency could be
 related to language acquisition in these lineages.
description: # Dryad dataset Dataset DOI:
 [10.5061/dryad.sbcc2frk5](10.5061/dryad.sbcc2frk5) ## Description of the
 data and file structure The data in this collection are supplemental to
 the paper "**Natural Selection and Language Genes in Humans".**
 DNA sequence matrices for 175 genes for 42 taxa can be found in
 "Lang_Supplemental_File1.zip". All sequences used to construct
 these matrices were obtained from GENBANK. These matrices were used to
 perform all tests for selection accomplished in the paper. We used
 DATAMONKEY ([https://www.datamonkey.org/](https://www.datamonkey.org/)).
 The study involves an examination of natural selection in these genes some
 of which are involved in language acquisition. Once we obtained measures
 of selection, genes obviously under selection were examined for
 interactions using STRING
 ([https://string-db.org/)](https://string-db.org/). ### Files and
 variables #### File: Language_Supplemental_File1.zip **Description:** This
 zip file holds phylogenetic matrices for 175 genes that we examined for
 natural selection. These files can be imported directly into DATAMONKEY
 ([https://www.datamonkey.org/](https://www.datamonkey.org/)) and analyzed
 using BUSTED, aBSREL and RELAX algorithms, using Lemurs as outgroups. This
 online program is freely available and can also be downloaded as a desktop
 standalone (announced in the following published paper:
 [https://pmc.ncbi.nlm.nih.gov/articles/PMC5850112/).](https://pmc.ncbi.nlm.nih.gov/articles/PMC5850112/) The files included in this zip archive are listed below. The file type is at the end of the name. Three file types are given here (.txt, .nex and .fasta). All three file types are compatible with DATAMONKEY. The naming convention of the files is as follows: the gene name is given first in capital letters. The information between the gene name and the file type describes the way the phylogenetic matrices were aligned. All files have a "nt_ali." indicating that the file is made of nucelotides that have been aligned using a codon aware algorithm (TranslatorX: a freely available alignment program see Abascal, Federico, Rafael Zardoya, and Maximilian J. Telford. "TranslatorX: multiple alignment of nucleotide sequences guided by amino acid translations." *Nucleic acids research* 38, no. suppl_2 (2010): W7-W13. and available at [http://161.111.160.230/index_v5.html](http://161.111.160.230/index_v5.html)). The "proteins", "res.", "mafft." and "DNA_sequence.txt" simply refer to the format of the data matrix before being converted to a TranslatorX codon aware alignment. ABDH8_proteins.txt.nt_ali.fasta ABDH8_res.nt_ali.fasta.nex ABDH8*_res.nt_ali.fasta ABTB3.BTBD11.mafft.txt.nt_ali.fasta ADSL_DNA_sequence.txt.nt_ali.fasta AKT1.sequence.txt.nt_ali.fasta ANXA1_mafft.txt.nt_ali.fasta BTB.12_mafft.txt.nt_ali.fasta.txt ARFGEF2.sequence.txt.nt_ali.fasta ARHGAP32_DNA_sequence.txt.nt_ali.fasta ARMCX2_res.nt_ali.fasta.nex ASPM.mafft.txt.nt_ali.fasta AUTS2_mafft.txt.nt_ali.clean.nex BCL2L1.mafft.txt.nt_ali.fasta BSN_sequence.txt.nt_ali.fasta CACNA1C_mafft.txt.nt_ali.fasta CACNA1C*_mafft.txt.nt_ali.fasta CACNA1E.sequence.txt.nt_ali.fasta CACNA1I_mafft.txt.nt_ali1.fasta CACNA1I_mafft.txt.nt_aliA.fasta CACNA1S_proteins.txt.nt_ali.fasta CACNA2D2.sequence.txt.nt_ali.fasta CACNB4.mafft.txt.nt_ali.fasta CDH13.mafft.txt.nt_ali.fasta CDKL5_res.nt_ali.fasta.nex CFAP99.mafft.txt.nt_ali.fasta CHEK1_proteins.txt.nt_ali.fasta CHRM3.mafft.txt.nt_ali.fasta CHRNA4_proteins.txt.nt_ali.fasta CLCN2.sequence.txt.nt_ali.fasta CLDN5.mafft.txt.nt_ali.fasta CLOCK.sequence.txt.nt_ali.fasta CNTNAP2.mafft.txt.nt_ali.fasta CNTNAP4.sequence.txt.nt_ali.fasta COMT.mafft.txt.nt_ali (modified).fasta CORO2B_proteins.txt.nt_ali.fasta CRHR1**.mafft.txt.nt_ali.fasta CSMD1.mafft.txt.nt_ali.fasta CSNK1G2_proteins.txt.nt_ali.fasta CTNNB1.mafft.txt.nt_ali.fasta CTNND2.mafft.txt.nt_ali.fasta CUX1.mafft.txt.nt_ali.fasta CUX2.mafft.txt.nt_ali.fasta DBN1.sequence.txt.nt_ali.fasta DCC.sequence.txt.nt_ali.fasta DGKQ_proteins.txt.nt_ali.fasta DHCR7_proteins.txt.nt_ali.fasta DISC1.sequence.txt.nt_ali.fasta DLG2.mafft.txt.nt_ali.fasta DNAAF4_DYX1C1_mafft.txt.nt_ali.fasta DRD1_proteins.txt.nt_ali.fasta DTNBP1_mafft.txt.nt_ali.fasta EDNRA.sequence.txt.nt_ali.fasta EDNRB.sequence.txt.nt_ali.fasta EGR3_proteins.txt.nt_ali.fasta EN2.mafft.txt.nt_ali.fasta EPN2_proteins.txt.nt_ali.fasta ESR1.mafft.txt.nt_ali.fasta EVC2_DNA_sequence.txt.nt_ali.fasta FGFR1.sequence.txt.nt_ali.fasta FGFR2.sequence.txt.nt_ali.fasta FILIP1_proteins.txt.nt_ali.fasta FOXP2.mafft.txt.nt_ali.fasta GABRA4.mafft.txt.nt_ali.fasta GABRB3.mafft.txt.nt_ali.fasta GABRG2_proteins.txt.nt_ali.fasta GGCX_DNA_sequence.txt.nt_ali.fasta GLRA2.mafft.txt.nt_ali.fasta GNPTAB.mafft.txt.nt_ali.fasta GPR83_proteins.txt.nt_ali.fasta GPR101_proteins.txt.nt_ali.fasta GRID2_mafft.txt.nt_ali.fasta GRIN2A_proteins.txt.nt_ali.fasta GRIN2B.mafft.txt.nt_ali.fasta GTF2I.sequence.txt.nt_ali.fasta HAPLN1.mafft.txt.nt_ali.fasta HSPBP1_proteins.txt.nt_ali.fasta HTR1A.sequence.txt.nt_ali.fasta HTR2B_DNA_sequence.txt.nt_ali.fasta IL1RAPL1.mafft.txt.nt_ali.fasta ITPR2.mafft.txt.nt_ali.fasta JAZF1_proteins.txt.nt_ali.fasta KATNA1_DNA_sequence.txt.nt_ali.fasta KATNA1_DNA_sequence.txt.nt_aliA.nex KCNA4_proteins.txt.nt_ali.fasta KCNC4_proteins.txt.nt_ali.fasta KCNC4_res.nt_ali.fasta KCNH1.mafft.txt.nt_ali.fasta KCNH8.mafft.txt.nt_ali.fasta KCNJ3_proteins.txt.nt_ali.fasta KCNK6.mafft.txt.nt_ali.fasta KCNS3.mafft.txt.nt_ali.fasta KCNT2_proteins.txt.nt_ali.fasta KIT.sequence.txt.nt_ali.fasta KRT90_res.nt_ali.fasta LGR6.mafft.txt.nt_ali.fasta LHX1_proteins.txt.nt_ali.fasta LRP2_proteins.txt.nt_ali.fasta LRRK2.mafft.txt.nt_ali.fasta LSAMP_mafft.txt.nt_ali.fasta LUZP1_DNA_sequence.txt.nt_ali.fasta LYNX1_proteins.txt.nt_ali.fasta MAD1l1.sequence.txt.nt_ali.fasta MAOA.mafft.txt.nt_ali.fasta MAPT.mafft.txt.nt_ali.fasta MCAT_proteins.txt.nt_ali.fasta MCPH1.mafft.txt.nt_ali.fasta MGLL_proteins.txt.nt_ali.fasta NAV3_proteins.txt.nt_ali.fasta NBPF3.mafft.txt.nt_ali.fasta NCAM1.sequence.txt.nt_ali.fasta NEFM.maafft.txt.nt_ali.fasta NLGN1.mafft.txt.nt_ali.fasta NOS1.mafft.txt.nt_ali.fasta NOVA1_DNA_sequence.txt.nt_ali.fasta NPAS1.sequence.txt.nt_ali.fasta NPAS3_proteins.txt.nt_ali.fasta NPSR1.mafft.txt.nt_ali.fasta NR4A2_proteins.txt.nt_ali.fasta NRCAM.mafft.txt.nt_ali.fasta NRXN1_mafft.txt.nt_ali.fasta NTRK2.mafft.txt.nt_ali.fasta OPRL1_proteins.txt.nt_ali.fasta PARK7.mafft.txt.nt_ali.fasta PCDH15.mafft.txt.nt_ali.fasta PCDH17.sequence.txt.nt_ali.fasta PCNT.mafft.txt.nt_ali.fasta PCOLCE2_proteins.txt.nt_ali.fasta PDE4B.mafft.txt.nt_ali.fasta POMT1_proteins.txt.nt_ali.fasta PRKCB.mafft.txt.nt_ali.fasta PRKCB**.mafft.txt.nt_ali.fasta RAPGEF4.mafft.txt.nt_ali.fasta RELN.mafft.txt.nt_ali.fasta RGMB_proteins.txt.nt_ali.fasta RIMS1**_res.nt_ali.fasta RNFT2_proteins.txt.nt_ali.fasta RPRM_proteins.txt.nt_ali.fasta RTN4R_proteins.txt.nt_ali.fasta S100B.mafft.txt.nt_ali.fasta SCAND1_proteins.txt.nt_ali.fasta SCN10A_proteins.txt.nt_ali.fasta SCN11A.mafft.txt.nt_ali.fasta SLC6A11.mafft.txt.nt_ali.fasta SLC6A12.mafft.txt.nt_ali.fasta SLC17A8.mafft.txt.nt_ali.fasta SLITRK1_DNA_sequence.txt.nt_ali.fasta Snap25_mafft.txt.nt_trim_ali.fasta SNTA1_proteins.txt.nt_ali.fasta SPP1.sequence.txt.nt_ali.fasta SRD5A1_proteins.txt.nt_ali.fasta SRGAP2_proteins.txt.nt_ali.fasta SST_proteins.txt.nt_ali.fasta STX8_proteins.txt.nt_ali.fasta STX11_proteins.txt.nt_ali.fasta STX16.mafft.txt.nt_ali.fasta SUSD6_proteins.txt.nt_ali.fasta SV2c_trimfix_align.fasta.nex SYNE1.mafft.txt.nt_ali.fasta SYT2.mafft.txt.nt_ali.fasta SYT7.sequence.txt.nt_ali.fasta TAC3_proteins.txt.nt_ali.fasta TF.mafft.txt.nt_ali.fasta THSD7B_proteins.txt.nt_ali.fasta TIAM1_MAFFT.txt.nt_ali.fasta TRPC4_proteins.txt.nt_ali.fasta UBASH3B.mafft.txt.nt_ali.fasta UBE2W_proteins.txt.nt_ali.fasta USP10.mafft.txt.nt_ali.fasta VAPA.mafft.txt.nt_ali.fasta VAT1L.mafft.txt.nt_ali.fasta VCAN_DNA_sequence.txt.nt_ali.fasta WFS1.mafft.txt.nt_ali.fasta WNK1.mafft.txt.nt_ali.fasta WNT7A_proteins.txt.nt_ali.fasta YIPF3_proteins.txt.nt_ali.fasta ZNF197.mafft.txt.nt_ali.fasta ZNF713_proteins.txt.nt_ali.fasta ZNRF1_proteins.txt.nt_ali.fasta #### File: Language_suppl_figures.pdf **Description:** This .pdf file holds the supplemental tables for "Natural Selection and Language Genes in Humans".  All figures were produced using STRING. Supplemental Figure S1. Interaction networks of two control gene sets. A. Network for 100 randomly chosen genes from the human genome. B. Network for the neural gene control dataset described in the text.   Supplemental Figure S2. A. Gene network for 21 randomly chosen control neural genes (out of 53). B. Gene network for 21 control genes randomly chosen from the human genome. C. Gene Network for 21 genes identified as under the aBSREL routine.  Three sub-networks are clear – 1) NPAS3-AUTS2-RELN-CUX2, 2) GABRG2-MCPH1 and 3) CACNA1E – CACNA2D2- CACNAIC- NOS1. #### Files: Supplemental_Table_S* **Supplemental_Table_S1.csv** Lists of candidate genes for language for 33 studies. The headers represent published articles used in the study that are discussed in "**Natural Selection and Language Genes in Humans"**. The candidate genes described in the listed publication are shown under the publication name. Under each header we list candidate genes, empty cells can be ignored. **Supplemental_Table_S2.csv** 1000 neural genes: lists 1000 genes thought to be involved in language as well as whether the gene had synonomous and nonsynonomous variation. There are four columns as described below. Under each header we list candidate genes, empty cells can be ignored. The four columns in the table are: A. Gene symbol (gene symbol for the 1000 genes) B. replacement only (whether the gene has replacement substitutions ONLY) C. silent only (whether the gene has silent substitutions ONLY) D. silent and replacement (whether the gene has BOTH silent and replacement substitutions) **Supplemental_Table_3A.csv** This Table contains lists of the candidate and control genes we used in tests for natural selection. We also indicate in this table whether or not the control genes have synonomous or nonsynonomous variation. Under each header we list control and candidate genes, empty cells can be ignored. There are three columns with the following content. A. Final candidate gene list B. Final control gene list C. Indicates whether the control gene in column B has synonomous or nonsynonomous variation. **Supplemental_Table_S3B.csv** This table contains Gene Lengths fpr all of the candidate genes. Under each header we list the genes, empty cells can be ignored. The six columns in the table are A. Candidate genes B. Candidate gene Length C. control genes with syn and nonsyn variation D. Length of genes with syn and nonsyn variation E. Control genes without syn or nonsyn variation F. Length of control genes without syn or nonsyn variation **Supplemental_Table_S4.csv** List of primate taxa used. Under the headers we list the taxon name and the abbreviation used in the study, empty cells can be ignored. The two columns are for the A. taxon abbreviation B taxon name. **Supplemental_Table_S5.csv** List of phylogenetic matrices used in the study. These files can be found in Supplemental File 1and the description of the file name components is given in the caption for Supplemental File 1. Empty cells can be ignored. NA indicares control genes that were not analyzed due to alignment problems. The four columns are for A. Candidate genes B. Cand_File_Name C. Control genes. D. Cont_File_Name **Supplemental_Table_S6.csv** Results of aBSREL, RELAX and BUSTED There are 25 columns in the table that describe the results of the aBSREL, RELAX and BUSTED tests as described in "**Natural Selection and Language Genes in Humans"**. Empty cells can be ignored. The columns labels are listed below and refer to: A. aBSREL-candidate gene: aBSREL-candidate genes and control genes tested B. Triad or Single: Indicates whether the tested group was the triad (sapiens+Neamderthal+Denisova) or a single taxon;"triad" indicates the triad node was tested; other listings indicate that either NEA (Neanderthal), Denisova (DEN) or SAP (sapiens) had identical sequences and the test was not done on the triad. C. aBSREL-Candidate/Control gene result: Result for the candidate and control genes using the aBSREL test with significance level; "NA" indicates not performed due to matrix size. D. RELAX: first screen: List of the 122 candidate genes tested using RELAX E. RELAX-Denisova/bb: Results of RELAX test for -Denisova/bb: Denisova vs primate backbone contrasted F. RELAX-Neanderthal/bb: Results of RELAX test for Neanderthal/bb: Neanderthal vs primate backbone contrasted G. RELAX-sapiens/bb: Results of RELAX test for sapiens/bb: sapiens vs primate backbone contrasted H. RELAX-triad/bb: Results of RELAX test for the triad/bb: (sapiens+Neamderthal+Denisova) vs primate backbone contrasted I. triad or single archaic: Indicates whether the test involved the triad or if Denisova and Neanderthal were identical J. RELAX-Candidate gene: Candidate genes testeed for multiple nodes: gene name of the 20 candidate genes with positive results from previous test K. DENvBB: Results of RELAX test for DENvBB: with Denisova vs primate backbone L. NEAvBB: Results of RELAX test for NEAvBB: with Neanderthal vs primate backbone M. SVBB: Results of RELAX test for SvBB: with sapiens vs primate backbone N. triadvBB: Results of RELAX test for triadvBB: with triad (sapiens+Neamderthal+Denisova) vs primate backbone O. apes: Results of RELAX test for apes : with apes vs rest of primate backbone P. C+triad: Results of RELAX test for C+triad: with chimps plus triad vs rest of primate backbone Q. G+C+triad: Results of RELAX test for G+C+triad: with gorillas, chimps plus triad vs rest of primate backbone R. BUSTED-candidate-gene: Candidate genes tested with BUSTED for the 122 candidate genes S. Triad: Whether or not the clade tested used the (sapiens+Neamderthal+Denisova) triad or if two of the triad were identical T. BUSTED-candidate gene -result: Results of BUSTED tests for 119 candidate genes U. BUSTED-control-gene: Control genes tested with BUSTED V. BUSTED-control gene -result: Results of BUSTED tests for 54 control genes W summary-aBSREL: gene list-summary-aBSRELgives list of genes detected using aBSREL X. summary-busted: gene list-summary-busted gives list of genes detected using BUSTED Y. summary-relax: gene list-summary-relax : list of genes detected using RELAX NP=not performed due to anomalies in matrix   ## Human subjects data There are no PPI data in this paper. Individuals are NOT identified.