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Bergqvist, Christina
Alternative names
Publications (10 of 12) Show all publications
Pedersen, J. E., Bergqvist, C. & Larhammar, D. (2019). Evolution of vertebrate nicotinic acetylcholine receptors. BMC Evolutionary Biology, 19, Article ID 38.
Open this publication in new window or tab >>Evolution of vertebrate nicotinic acetylcholine receptors
2019 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 19, article id 38Article in journal (Refereed) Published
Abstract [en]

Background

Many physiological processes are influenced by nicotinic acetylcholine receptors (nAChR), ranging from neuromuscular and parasympathetic signaling to modulation of the reward system and long-term memory. Due to the complexity of the nAChR family and variable evolutionary rates among its members, their evolution in vertebrates has been difficult to resolve. In order to understand how and when the nAChR genes arose, we have used a broad approach of analyses combining sequence-based phylogeny, chromosomal synteny and intron positions.

Results

Our analyses suggest that there were ten subunit genes present in the vertebrate predecessor. The two basal vertebrate tetraploidizations (1R and 2R) then expanded this set to 19 genes. Three of these have been lost in mammals, resulting in 16 members today. None of the ten ancestral genes have kept all four copies after 2R. Following 2R, two of the ancestral genes became triplicates, five of them became pairs, and three seem to have remained single genes. One triplet consists of CHRNA7, CHRNA8 and the previously undescribed CHRNA11, of which the two latter have been lost in mammals but are still present in lizards and ray-finned fishes. The other triplet consists of CHRNB2, CHRNB4 and CHRNB5, the latter of which has also been lost in mammals. In ray-finned fish the neuromuscular subunit gene CHRNB1 underwent a local gene duplication generating CHRNB1.2. The third tetraploidization in the predecessor of teleosts (3R) expanded the repertoire to a total of 31 genes, of which 27 remain in zebrafish. These evolutionary relationships are supported by the exon-intron organization of the genes.

Conclusion

The tetraploidizations explain all gene duplication events in vertebrates except two. This indicates that the genome doublings have had a substantial impact on the complexity of this gene family leading to a very large number of members that have existed for hundreds of millions of years.

National Category
Evolutionary Biology Cell Biology Biochemistry and Molecular Biology Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-353919 (URN)10.1186/s12862-018-1341-8 (DOI)000457255700002 ()30700248 (PubMedID)
Funder
The Swedish Brain FoundationCarl Tryggers foundation
Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2019-02-25Bibliographically approved
Pedersen, J. E., Bergqvist, C. & Larhammar, D. (2018). Evolution of the muscarinic acetylcholine receptors in vertebrates. eNeuro, 5(5), Article ID UNSP e0340-18.2018.
Open this publication in new window or tab >>Evolution of the muscarinic acetylcholine receptors in vertebrates
2018 (English)In: eNeuro, ISSN 2373-2822, Vol. 5, no 5, article id UNSP e0340-18.2018Article in journal (Refereed) Published
Abstract [en]

The family of muscarinic acetylcholine receptors (mAChRs) consists of five members in mammals, encoded by theCHRM1-5 genes. The mAChRs are G-protein-coupled receptors, which can be divided into the following two subfamilies: M2 and M4 receptors coupling to Gi/o; and M1, M3, and M5 receptors coupling to Gq/11. However, despite the fundamental roles played by these receptors, their evolution in vertebrates has not yet been fully described. We have combined sequence-based phylogenetic analyses with comparisons of exon–intron organi- zation and conserved synteny in order to deduce the evolution of the mAChR receptors. Our analyses verify the existence of two ancestral genes prior to the two vertebrate tetraploidizations (1R and 2R). After these events, one gene had duplicated, resulting in CHRM2 and CHRM4; and the other had triplicated, forming the CHRM1,CHRM3, and CHRM5 subfamily. All five genes are still present in all vertebrate groups investigated except theCHRM1 gene, which has not been identified in some of the teleosts or in chicken or any other birds. Interestingly, the third tetraploidization (3R) that took place in the teleost predecessor resulted in duplicates of all five mAChR genes of which all 10 are present in zebrafish. One of the copies of the CHRM2 and CHRM3 genes and bothCHRM4 copies have gained introns in teleosts. Not a single separate (nontetraploidization) duplicate has been identified in any vertebrate species. These results clarify the evolution of the vertebrate mAChR family and reveal a doubled repertoire in zebrafish, inviting studies of gene neofunctionalization and subfunctionalization.

Keywords
acetylcholine, G-protein-coupled receptor, gene duplication, muscarinic, tetraploidization, zebrafish
National Category
Neurology
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-371818 (URN)10.1523/ENEURO.0340-18.2018 (DOI)000456897300002 ()30564629 (PubMedID)
Funder
Carl Tryggers foundation
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2019-01-02 Created: 2019-01-02 Last updated: 2019-02-18Bibliographically approved
Larhammar, D., Bergqvist, C. A. & Sundström, G. (2015). Ancestral vertebrate complexity of the opioid system. In: Gerald Litwack (Ed.), Nociceptin Opioid: . Academic Press
Open this publication in new window or tab >>Ancestral vertebrate complexity of the opioid system
2015 (English)In: Nociceptin Opioid / [ed] Gerald Litwack, Academic Press, 2015Chapter in book (Refereed)
Abstract [en]

The evolution of the opioid peptides and nociceptin/orphanin as well as their receptors has been difficult to resolve due to variable evolutionary rates. By combining sequence comparisons with information on the chromosomal locations of the genes, we have deduced the following evolutionary scenario: The vertebrate predecessor had one opi- oid precursor gene and one receptor gene. The two genome doublings before the ver- tebrate radiation resulted in three peptide precursor genes whereupon a fourth copy arose by a local gene duplication. These four precursors diverged to become the pre- propeptides for endorphin (POMC), enkephalins, dynorphins, and nociceptin, respec- tively. The ancestral receptor gene was quadrupled in the genome doublings leading to delta, kappa, and mu and the nociceptin/orphanin receptor. This scenario is corroborated by new data presented here for coelacanth and spotted gar, rep- resenting two basal branches in the vertebrate tree. A third genome doubling in the ancestor of teleost fishes generated additional gene copies. These results show that the opioid system was quite complex already in the first vertebrates and that it has more components in teleost fishes than in mammals. From an evolutionary point of view, nociceptin and its receptor can be considered full-fledged members of the opioid system. 

Place, publisher, year, edition, pages
Academic Press, 2015
Series
Vitamins and Hormones, ISSN 0083-6729 ; 97
Keywords
Neuropeptide, receptor, evolution, opioid
National Category
Natural Sciences
Research subject
Evolutionary Genetics; Neuroscience
Identifiers
urn:nbn:se:uu:diva-240040 (URN)10.1016/bs.vh.2014.11.001 (DOI)978-0-12-802443-0 (ISBN)
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2019-01-03
Xu, B., Bergqvist, C. A., Sundström, G., Lundell, I., Vaudry, H., Leprince, J. & Larhammar, D. (2015). Characterization of peptide QRFP (26RFa) and its receptor from amphioxus, Branchiostoma floridae. General and Comparative Endocrinology, 210, 107-113
Open this publication in new window or tab >>Characterization of peptide QRFP (26RFa) and its receptor from amphioxus, Branchiostoma floridae
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2015 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 210, p. 107-113Article in journal (Refereed) Published
Abstract [en]

A peptide ending with RFamide (Arg-Phe-amide) was discovered independently by three different laboratories in 2003 and named 26RFa or QRFP. In mammals, a longer version of the peptide, 43 amino acids, was identified and found to bind to the orphan G protein-coupled receptor GPR103. We searched the genome database of Branchiostoma floridae (Bfl) for receptor sequences related to those that bind peptides ending with RFa or RYa (including receptors for NPFF, PRLH, GnIH, and NPY). One receptor clustered in phylogenetic analyses with mammalian QRFP receptors. The gene has 3 introns in Bfl and 5 in human, but all intron positions differ, implying that the introns were inserted independently. A QRFP-like peptide consisting of 25 amino acids and ending with RFa was identified in the amphioxus genome. Eight of the ten last amino acids are identical between Bfl and human. The prepro-QRFP gene in Bfl has one intron in the propeptide whereas the human gene lacks introns. The Bfl QRFP peptide was synthesized and the receptor was functionally expressed in human cells. The response was measured as inositol phosphate (IP) turnover. The Bfl QRFP peptide was found to potently stimulate the receptor's ability to induce IP turnover with an EC50 of 0.28nM. Also the human QRFP peptides with 26 and 43 amino acids were found to stimulate the receptor (1.9 and 5.1nM, respectively). Human QRFP with 26 amino acids without the carboxyterminal amide had dramatically lower potency at 1.3μM. Thus, we have identified an amphioxus QRFP-related peptide and a corresponding receptor and shown that they interact to give a functional response.

Keywords
Neuropeptide, receptor, evolution
National Category
Neurosciences
Research subject
Evolutionary Genetics; Neuroscience
Identifiers
urn:nbn:se:uu:diva-240039 (URN)10.1016/j.ygcen.2014.10.010 (DOI)000346886400012 ()25449662 (PubMedID)
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2019-01-03Bibliographically approved
Tostivint, H., Ocampo Daza, D., Bergqvist, C., Quan, F. B., Bougerol, M., Lihrmann, I. & Larhammar, D. (2014). Molecular evolution of GPCRS:: somatostatin/urotensin II receptors. Journal of Molecular Endocrinology, 52, T61-86
Open this publication in new window or tab >>Molecular evolution of GPCRS:: somatostatin/urotensin II receptors
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2014 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 52, p. T61-86Article in journal (Refereed) Published
Abstract [en]

Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand-receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

Keywords
neuropeptides, somatostatin, urotensin II, GPCR, mutigene families, duplication, tetraploidization
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-229057 (URN)10.1530/JME-13-0274 (DOI)000343056500011 ()
Available from: 2014-07-28 Created: 2014-07-28 Last updated: 2019-01-03Bibliographically approved
Cardoso, J. C., Félix, R. C., Bergqvist, C. A. & Larhammar, D. (2014). New insights into the evolution of vertebrate CRH (corticotropin-releasing hormone) and invertebrate DH44 (diuretic hormone 44) receptors in metazoans. General and Comparative Endocrinology, 209(SI), 162-170
Open this publication in new window or tab >>New insights into the evolution of vertebrate CRH (corticotropin-releasing hormone) and invertebrate DH44 (diuretic hormone 44) receptors in metazoans
2014 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 209, no SI, p. 162-170Article in journal (Refereed) Published
Abstract [en]

The corticotropin releasing hormone receptors (CRHR) and the arthropod diuretic hormone 44 receptors (DH44R) are structurally and functionally related members of the G protein-coupled receptors (GPCR) of the secretin-like receptor superfamily. We show here that they derive from a bilaterian predecessor. In protostomes, the receptor became DH44R that has been identified and functionally characterised in several arthropods but the gene seems to be absent from nematode genomes. Duplicate DH44R genes (DH44 R1 and DH44R2) have been described in some arthropods resulting from lineage-specific duplications. Recently, CRHR-DH44R-like receptors have been identified in the genomes of some lophotrochozoans (molluscs, which have a lineage-specific gene duplication, and annelids) as well as representatives of early diverging deuterostomes. Vertebrates have previously been reported to have two CRHR receptors that were named CRHR1 and CRHR2. To resolve their origin we have analysed recently assembled genomes from representatives of early vertebrate divergencies including elephant shark, spotted gar and coelacanth. We show here by analysis of synteny conservation that the two CRHR genes arose from a common ancestral gene in the early vertebrate tetraploidizations (2R) approximately 500 million years ago. Subsequently, the teleost-specific tetraploidization (3R) resulted in a duplicate of CRHR1 that has been lost in some teleost lineages. These results help distinguish orthology and paralogy relationships and will allow studies of functional conservation and changes during evolution of the individual members of the receptor family and their multiple native peptide agonists.

Keywords
Neuropeptide, receptor, evolution
National Category
Neurosciences
Research subject
Evolutionary Genetics; Neuroscience
Identifiers
urn:nbn:se:uu:diva-240035 (URN)10.1016/j.ygcen.2014.09.004 (DOI)000346890500015 ()25230393 (PubMedID)
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2019-01-03Bibliographically approved
Larhammar, D., Xu, B. & Bergqvist, C. A. (2014). Unexpected multiplicity of QRFP receptors in early vertebrate evolution. Frontiers in Neuroscience, 8, 337
Open this publication in new window or tab >>Unexpected multiplicity of QRFP receptors in early vertebrate evolution
2014 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, p. 337-Article in journal (Refereed) Published
Abstract [en]

The neuropeptide QRFP, also called 26RFa, and its G protein-coupled receptor GPR103 have been identified in all vertebrates investigated. In mammals, this peptide-receptor pair has been found to have several effects including stimulation of appetite. Recently, we reported that a QRFP peptide is present in amphioxus, Branchiostoma floridae, and we also identified a QRFP receptor (QRFPR) that mediates a functional response to sub-nanomolar concentrations of the amphioxus peptide as well as short and long human QRFP (Xu et al., submitted). Because the ancestral vertebrate underwent two tetraploidizations, it might be expected that duplicates of the QRFP gene and its receptor gene may exist. Indeed, we report here the identification of multiple vertebrate QRFPR genes. Three QRFPR genes are present in the coelacanth Latimeria chalumnae, representing an early diverging sarcopterygian lineage. Three QRFPR genes are present in the basal actinopterygian fish, the spotted gar. Phylogenetic and chromosomal analyses show that only two of these receptor genes are orthologous between the two species, thus demonstrating a total of four distinct vertebrate genes. Three of the QRFPR genes resulted from the early vertebrate tetraploidizations and were copied along with syntenic neuropeptide Y receptor genes. The fourth QRFPR gene may be an even older and distinct lineage. Because mammals and birds have only a single QRFPR gene, this means that three genes have been lost in these lineages, and at least one of these was lost independently in mammals and birds because it is still present in a turtle. In conclusion, these results show that the QRFP system gained considerable complexity in the early stages of vertebrate evolution and still maintains much of this in some lineages, and that it has been secondarily reduced in mammals.

Keywords
Neuropeptide, receptor, evolution
National Category
Natural Sciences
Research subject
Neuroscience; Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-240037 (URN)10.3389/fnins.2014.00337 (DOI)000346532900001 ()25386115 (PubMedID)
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2019-01-03Bibliographically approved
Larhammar, D. & Bergqvist, C. A. (2013). Ancient Grandeur of the Vertebrate Neuropeptide Y System Shown by the Coelacanth Latimeria chalumnae. Frontiers in Neuroscience, 7, Article ID 27.
Open this publication in new window or tab >>Ancient Grandeur of the Vertebrate Neuropeptide Y System Shown by the Coelacanth Latimeria chalumnae
2013 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 7, article id 27Article in journal (Refereed) Published
Abstract [en]

The neuropeptide Y (NPY) family receptors and peptides have previously been characterized in several tetrapods, teleost fishes, and in a holocephalan cartilaginous fish. This has shown that the ancestral NPY system in the jawed vertebrates consisted of the peptides NPY and peptide YY (PYY) and seven G-protein-coupled receptors named Y1-Y8 (Y3 does not exist). The different vertebrate lineages have subsequently lost or gained a few receptor genes. For instance, the human genome has lost three of the seven receptors while the zebrafish has lost two and gained two receptor genes. Here we describe the NPY system of a representative of an early diverging lineage among the sarcopterygians, the West Indian Ocean coelacanth Latimeria chalumnae. The coelacanth was found to have retained all seven receptors from the ancestral jawed vertebrate. The receptors display the typical characteristics found in other vertebrates. Interestingly, the coelacanth was found to have the local duplicate of the PYY gene, called pancreatic polypeptide, previously only identified in tetrapods. Thus, this duplication took place very early in the sarcopterygian lineage, before the origin of tetrapods. These findings confirm the ancient complexity of the NPY system and show that mammals have lost more NPY receptors than any other vertebrate lineage. The coelacanth has all three peptides found in tetrapods and has retained the ancestral jawed vertebrate receptor repertoire with neither gains or losses.

Keywords
Evolution, genome duplication, NPY, elephant shark
National Category
Natural Sciences Neurology
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-205598 (URN)10.3389/fnins.2013.00027 (DOI)000346567300027 ()23483106 (PubMedID)
Funder
Swedish Research Council
Available from: 2013-08-20 Created: 2013-08-20 Last updated: 2019-01-03Bibliographically approved
Sundström, G., Xu, B., Larsson, T. A., Heldin, J., Bergqvist, C. A., Fredriksson, R., . . . Larhammar, D. (2012). Characterization of the neuropeptide Y system in the frog Silurana tropicalis (Pipidae): three peptides and six receptor subtypes. General and Comparative Endocrinology, 177(3), 322-331
Open this publication in new window or tab >>Characterization of the neuropeptide Y system in the frog Silurana tropicalis (Pipidae): three peptides and six receptor subtypes
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2012 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 177, no 3, p. 322-331Article in journal (Refereed) Published
Abstract [en]

Neuropeptide Y and its related peptides PYY and PP (pancreatic polypeptide) are involved in feeding behavior, regulation of the pituitary and the gastrointestinal tract, and numerous other functions. The peptides act on a family of G-protein coupled receptors with 4-7 members in jawed vertebrates. We describe here the NPY system of the Western clawed frog Silurana (Xenopus) tropicalis. Three peptides, NPY, PYY and PP, were identified together with six receptors, namely subtypes Y1, Y2, Y4, Y5, Y7 and Y8. Thus, this frog has all but one of the ancestral seven gnathostome NPY-family receptors, in contrast to mammals which have lost 2-3 of the receptors. Expression levels of mRNA for the peptide and receptor genes were analyzed in a panel of 19 frog tissues using reverse transcriptase quantitative PCR. The peptide mRNAs had broad distribution with highest expression in skin, blood and small intestine. NPY mRNA was present in the three brain regions investigated, but PYY and PP mRNAs were not detectable in any of these. All receptor mRNAs had similar expression profiles with high expression in skin, blood, muscle and heart. Three of the receptors, Y5, Y7 and Y8, could be functionally expressed in HEK-293 cells and characterized with binding studies using the three frog peptides. PYY had the highest affinity for all three receptors (K(i) 0.042-0.34 nM). Also NPY and PP bound to the Y8 receptor with high affinity (0.14 and 0.50 nM). The low affinity of NPY for the Y5 receptor (100-fold lower than PYY) differs from mammals and chicken. This may suggest a less important role of NPY on Y5 in appetite stimulation in the frog compared with amniotes. In conclusion, our characterization of the NPY system in S. tropicalis with its six receptors demonstrates not only greater complexity than in mammals but also some interesting differences in ligand-receptor preferences.

Keywords
NPY, PYY, G-protein-coupled receptor, Silurana tropicalis, evolution
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-129517 (URN)10.1016/j.ygcen.2012.04.027 (DOI)000306390100005 ()22565163 (PubMedID)
Note

Erratum in General and Comparative Endocrinology 2015:215, doi:10.1016/j.ygcen.2014.11.014.

Available from: 2010-08-18 Created: 2010-08-18 Last updated: 2019-01-03Bibliographically approved
Ocampo Daza, D., Sundström, G., Bergqvist, C. & Larhammar, D. (2012). The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements.. BMC Evolutionary Biology, 12, 231
Open this publication in new window or tab >>The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements.
2012 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 12, p. 231-Article in journal (Refereed) Published
Abstract [en]

Background: Somatostatin and its related neuroendocrine peptides have a wide varietyof physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results: We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomalrearrangements. These events obscure the paralogy relationships but are still tractable thanks tothe many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions: Two ancestral SSTR-bearing chromosome regions were duplicated in the two basalvertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

Keywords
Somatostatin receptors, Whole genome duplications, Chromosome rearrangements
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-189967 (URN)10.1186/1471-2148-12-231 (DOI)000314219500001 ()
Available from: 2013-01-05 Created: 2013-01-05 Last updated: 2019-01-03Bibliographically approved
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