The repertoire of family A-peptide GPCRs in archaic hominins
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The repertoire of family A-peptide GPCRs in archaic hominins. / Mata, Xavier; Renaud, Gabriel; Mollereau, Catherine.
I: Peptides, Bind 122, 170154, 12.2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The repertoire of family A-peptide GPCRs in archaic hominins
AU - Mata, Xavier
AU - Renaud, Gabriel
AU - Mollereau, Catherine
PY - 2019/12
Y1 - 2019/12
N2 - Given the importance of G-protein coupled receptors in the regulation of many physiological functions, deciphering the relationships between genotype and phenotype in past and present hominin GPCRs is of main interest to understand the evolutionary process that contributed to the present-day variability in human traits and health. Here, we carefully examined the publicly available genomic and protein sequence databases of the archaic hominins (Neanderthal and Denisova) to draw up the catalog of coding variations in GPCRs for peptide ligands, in comparison with living humans. We then searched in the literature the functional changes, phenotypes and risk of disease possibly associated with the detected variants. Our survey suggests that Neanderthal and Denisovan hominins were likely prone to lower risk of obesity, to enhanced platelet aggregation in response to thrombin, to better response to infection, to less anxiety and aggressiveness and to favorable sociability. While some archaic variants were likely advantageous in the past, they might be responsible for maladaptive disorders today in the context of modern life and/or specific regional distribution. For example, an archaic haplotype in the neuromedin receptor 2 is susceptible to confer risk of diabetic nephropathy in type 1 diabetes in present-day Europeans. Paying attention to the pharmacological properties of some of the archaic variants described in this study may be helpful to understand the variability of therapeutic efficacy between individuals or ethnic groups.
AB - Given the importance of G-protein coupled receptors in the regulation of many physiological functions, deciphering the relationships between genotype and phenotype in past and present hominin GPCRs is of main interest to understand the evolutionary process that contributed to the present-day variability in human traits and health. Here, we carefully examined the publicly available genomic and protein sequence databases of the archaic hominins (Neanderthal and Denisova) to draw up the catalog of coding variations in GPCRs for peptide ligands, in comparison with living humans. We then searched in the literature the functional changes, phenotypes and risk of disease possibly associated with the detected variants. Our survey suggests that Neanderthal and Denisovan hominins were likely prone to lower risk of obesity, to enhanced platelet aggregation in response to thrombin, to better response to infection, to less anxiety and aggressiveness and to favorable sociability. While some archaic variants were likely advantageous in the past, they might be responsible for maladaptive disorders today in the context of modern life and/or specific regional distribution. For example, an archaic haplotype in the neuromedin receptor 2 is susceptible to confer risk of diabetic nephropathy in type 1 diabetes in present-day Europeans. Paying attention to the pharmacological properties of some of the archaic variants described in this study may be helpful to understand the variability of therapeutic efficacy between individuals or ethnic groups.
KW - Denisova
KW - GPCR
KW - Missense variants
KW - Neanderthal
KW - Peptides
U2 - 10.1016/j.peptides.2019.170154
DO - 10.1016/j.peptides.2019.170154
M3 - Journal article
C2 - 31560950
AN - SCOPUS:85073109976
VL - 122
JO - Peptides
JF - Peptides
SN - 0196-9781
M1 - 170154
ER -
ID: 230201150