Abstract
BackgroundPublicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations.ResultsWe identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans.ConclusionsWe compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.
Highlights
Available genome data provides valuable information on the genetic variation patterns across different modern human populations
We filtered out 125,372 indels variants and retained a total number of 644,225 single nucleotide polymorphisms (SNP) for downstream analysis because ancestral alleles could not be obtained for the indels
Variants in four of these genes (NPPA, CHGB, IGF2 and INS) were especially striking because of the following salient features: NPPA with a high impact stop lost variant; CHGB with multiple moderate impact missense variants; IGF2 and INS with moderate impact missense variants that are in linkage disequilibrium
Summary
Available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. Neuropeptides act as peptide hormones regulating functions such as feeding behavior, reproduction, stress response, energy homeostasis, cognition, pain and blood pressure. They perform their physiological processes by binding to corresponding receptors [7] and an abundance of neuropeptides has been reported in almost every system of the human body [4, 6, 8]. From over 1000 predicted peptides encoded in the human genome, there are over 100 known neuropeptide genes in the human and undoubtedly many more that are yet to be identified and annotated [9]
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