A bioinformatics study of NAGPA, GNPTAB and GNPTG, three genes likely involved in the development of speech and language in homo sapiens

Complex traits, such as language and speech in Homo sapiens, typically have a polygenic basis, and it is therefore highly improbable that exclusively FOXP2 – the only gene currently known to be specifically implicated in the development of linguistic processes – was selected in the evolution of our language abilities. Thus, with the purpose of examining the possible contribution of other genes to the evolution of language and speech in humans, in this study we performed an extensive bioinformatics analysis of the expression of the genes NAGPA, GNPTAB and GNPTG (mutations of which have previously been linked to speech disorders) in Homo sapiens, Pan troglodytes and other non-human primates, mammals and vertebrates, in order to examine their molecular evolution. By comparing protein-coding nucleotide sequences and encoded amino-acid sequences, we found, most notably, a few amino-acid substitutions between Homo sapiens and our closest living evolutionary relative, the chimpanzee, in each of the protein sequences encoded by these three genes, and we have determined the functional value of each replacement. All three genes are derived in humans relative to chimpanzees, and there is one amino-acid replacement with a high functional value in both the enzymes that are encoded by them, and which have evolved in the human lineage. Although the results of evolutionary analyses indicate that these genes are globally under purifying selection in Primates, similarly this occurs with FOXP2. The human FOXP2 protein differs from the chimpanzee sequence in just two replacements, which should, nevertheless, be regarded as strongly linked to human language acquisition, even though they can not be seen to have a high functional value. It appears, therefore, reasonable to infer that the genes GNPTAB, GNPTG, and particularly, NAGPA, might also have had a role in the evolution of human language.