Article | Published:

The genetic basis of parental care evolution in monogamous mice

Nature volume 544, pages 434439 (27 April 2017) | Download Citation

Abstract

Parental care is essential for the survival of mammals, yet the mechanisms underlying its evolution remain largely unknown. Here we show that two sister species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and heritable differences in parental behaviour. Using quantitative genetics, we identify 12 genomic regions that affect parental care, 8 of which have sex-specific effects, suggesting that parental care can evolve independently in males and females. Furthermore, some regions affect parental care broadly, whereas others affect specific behaviours, such as nest building. Of the genes linked to differences in nest-building behaviour, vasopressin is differentially expressed in the hypothalamus of the two species, with increased levels associated with less nest building. Using pharmacology in Peromyscus and chemogenetics in Mus, we show that vasopressin inhibits nest building but not other parental behaviours. Together, our results indicate that variation in an ancient neuropeptide contributes to interspecific differences in parental care.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Primary accessions

BioProject

References

  1. 1.

    & The evolution of social monogamy in mammals. Science 341, 526–530 (2013)

  2. 2.

    et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757 (2004)

  3. 3.

    , , , & Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain. Science 350, 1371–1374 (2015)

  4. 4.

    , & Role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster). Proc. Natl Acad. Sci. USA 91, 400–404 (1994)

  5. 5.

    & Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: from central release to sites of action. Horm. Behav. 61, 293–303 (2012)

  6. 6.

    , & Neural control of maternal and paternal behaviors. Science 345, 765–770 (2014)

  7. 7.

    , , & A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion. Nature 525, 519–522 (2015)

  8. 8.

    et al. Monogamy evolves through multiple mechanisms: evidence from V1aR in deer mice. Mol. Biol. Evol. 27, 1269–1278 (2010)

  9. 9.

    & Occurrence of successful multiple insemination of females in natural populations of deer mice (Peromyscus maniculatus). Evolution 27, 106–110 (1973)

  10. 10.

    Aggression, copulation, and differential reproduction of deer mice (Peromyscus maniculatus) in a semi-natural enclosure. Behaviour 91, 1–23 (1984)

  11. 11.

    & Copulatory behavior of old-field mice (Peromyscus polionotus) from different natural populations. Behav. Genet. 4, 347–355 (1974)

  12. 12.

    Genetic evidence for long-term monogamy in a small rodent, Peromyscus polionotus. Am. Nat. 117, 665–675 (1981)

  13. 13.

    An exercise in the prediction of monogamy in the field from laboratory data on 42 species of muroid rodents. Biologist 63, 138–162 (1981)

  14. 14.

    , , , & Double digest RADseq: an inexpensive method for de novo SNP discovery and genotyping in model and non-model species. PLoS ONE 7, e37135 (2012)

  15. 15.

    et al. Multiplexed shotgun genotyping for rapid and efficient genetic mapping. Genome Res. 21, 610–617 (2011)

  16. 16.

    ., & The Evolution of Parental Care (Oxford Univ. Press, 2012)

  17. 17.

    , , , & Predicting the functional effect of amino acid substitutions and indels. PLoS ONE 7, e46688 (2012)

  18. 18.

    et al. Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes. Biochim. Biophys. Acta Bioenerg. 1797, 1500–1511 (2010)

  19. 19.

    , , & Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF 3. Cell 122, 669–682 (2005)

  20. 20.

    et al. Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts. Blood 117, 6928–6938 (2011)

  21. 21.

    , , , & Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptor α4 impairs thyroid calcitonin production in young mice. Endocrinology 147, 2237–2244 (2006)

  22. 22.

    Medial preoptic area and maternal behavior in the female rat. J. Comp. Physiol. Psychol. 87, 746–759 (1974)

  23. 23.

    & Lesions of the hypothalamic paraventricular nucleus disrupt the initiation of maternal behavior. Physiol. Behav. 45, 1033–1041 (1989)

  24. 24.

    The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron 65, 768–779 (2010)

  25. 25.

    , , & Estrogen receptor α and vasopressin in the paraventricular nucleus of the hypothalamus in Peromyscus. Brain Res. 1032, 154–161 (2005)

  26. 26.

    & Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci. 35, 649–659 (2012)

  27. 27.

    , , & Differences in the number of arginine-vasopressin-immunoreactive neurons exist in the suprachiasmatic nuclei of house mice selected for differences in nest-building behavior. Brain Res. 578, 335–338 (1992)

  28. 28.

    & Genetic contributions to behavioural diversity at the gene–environment interface. Nat. Rev. Genet. 12, 809–820 (2011)

  29. 29.

    Sex differences in adult and developing brains: compensation, compensation, compensation. Endocrinology 145, 1063–1068 (2004)

  30. 30.

    The hierarchical organization of nervous mechanisms underlying instinctive behaviour. Symp. Soc. Exp. Biol. 4, 305–312 (1950)

  31. 31.

    et al. Internal states and behavioral decision-making: toward an integration of emotion and cognition. Cold Spring Harb. Symp. Quant. Biol. 79, 199–210 (2014)

  32. 32.

    , , & CNS arousal mechanisms bearing on sex and other biologically regulated behaviors. Physiol. Behav. 88, 283–293 (2006)

  33. 33.

    , , , & Galanin neurons in the medial preoptic area govern parental behaviour. Nature 509, 325–330 (2014)

  34. 34.

    , & The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. Neuroscience 43, 623–630 (1991)

  35. 35.

    & Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322, 900–904 (2008)

  36. 36.

    Fertility and size inheritance in a Peromyscus species cross. Evolution 19, 44–55 (1965)

  37. 37.

    & Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009)

  38. 38.

    & Stampy: a statistical algorithm for sensitive and fast mapping of Illumina sequence reads. Genome Res. 21, 936–939 (2011)

  39. 39.

    et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinformatics 11, 11.10.1–11.10.33 (2013)

  40. 40.

    A comparative study of the chromosomes of mammals. Am. Nat. 59, 385–409 (1925)

  41. 41.

    et al. Cytogenetic nomenclature of deer mice, Peromyscus (Rodentia): revision and review of the standardized karyotype. Report of the Committee for the Standardization of Chromosomes of Peromyscus. Cytogenet. Cell Genet. 66, 181–195 (1994)

  42. 42.

    . & mclust version 4 for R: normal mixture modeling for model-based clustering, classification, and density estimation (Department of Statistics, University of Washington, 2012)

  43. 43.

    R/qtlcharts: interactive graphics for quantitative trait locus mapping. Genetics 199, 359–361 (2015)

  44. 44.

    et al. A genetic map of Peromyscus with chromosomal assignment of linkage groups (a Peromyscus genetic map). Mamm. Genome 25, 160–179 (2014)

  45. 45.

    et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)

  46. 46.

    , , , & Evolution of multiple additive loci caused divergence between Drosophila yakuba and D. santomea in wing rowing during male courtship. PLoS ONE 7, e43888 (2012)

  47. 47.

    & Genetics and Analysis of Quantitative Traits 469–476 (Sinauer, 1998)

  48. 48.

    , , & R/qtl: QTL mapping in experimental crosses. Bioinformatics 19, 889–890 (2003)

  49. 49.

    et al. Adult mouse brain gene expression patterns bear an embryologic imprint. Proc. Natl Acad. Sci. USA 102, 10357–10362 (2005)

  50. 50.

    et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013)

  51. 51.

    et al. AlleleSeq: analysis of allele-specific expression and binding in a network framework. Mol. Syst. Biol. 7, 522 (2011)

  52. 52.

    & RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011)

  53. 53.

    et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015)

  54. 54.

    , , & voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014)

  55. 55.

    & A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010)

  56. 56.

    & Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289–300 (1995)

  57. 57.

    et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly 6, 80–92 (2012)

  58. 58.

    , & Clearance of vasopressin from cerebrospinal fluid to blood in chronically cannulated Brattleboro rats. Neuroendocrinology 37, 242–247 (1983)

  59. 59.

    & Differential effects of centrally injected AVP on heart rate, core temperature, and behavior in rats. Am. J. Physiol. 264, R51–R61 (1993)

  60. 60.

    , , & Oxytocin induces maternal behavior in virgin female rats. Science 216, 648–650 (1982)

  61. 61.

    , & Oxytocin induction of short-latency maternal behavior in nulliparous, estrogen-primed female rats. Horm. Behav. 18, 267–286 (1984)

  62. 62.

    , , , & A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365, 545–548 (1993)

  63. 63.

    , , , & Maternal care differs in mice bred for high vs. low trait anxiety: impact of brain vasopressin and cross-fostering. Soc. Neurosci. 6, 156–168 (2011)

  64. 64.

    & Brain vasopressin is an important regulator of maternal behavior independent of dams’ trait anxiety. Proc. Natl Acad. Sci. USA 105, 17139–17144 (2008)

  65. 65.

    , , , & Neuromolecular basis of parental behavior in laboratory mice and rats: with special emphasis on technical issues of using mouse genetics. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 1205–1231 (2011)

  66. 66.

    et al. Modular genetic control of sexually dimorphic behaviors. Cell 148, 596–607 (2012)

Download references

Acknowledgements

E. Kingsley shared unpublished data. D. Stern, P. Andolfatto, and A. Kitzmiller helped implement MSG; V. Bajic helped with anchoring genomic scaffolds; M. Khadraoui with allele-specific expression analysis; K. Turner with ddRAD library construction. Computations were run on the Odyssey cluster supported by the Harvard FAS Research Computing Group. R. Hellmiss provided advice on figures. C. Bargmann and P. McGrath provided comments on the manuscript. This work was supported by a Helen Hay Whitney Foundation Postdoctoral Fellowship and a National Institutes of Health (NIH) K99 award HD084732 to A.B., Harvard Museum of Comparative Zoology Grants in Aid and Harvard Undergraduate Research Fellowships to Y.-M.K., a European Molecular Biology Organization (ALTF 379-2011), Human Frontier Science Program, and Belgian American Educational Foundation fellowships to J.-M.L., NIH training grant GM008313 (to M.X.H.), National Philanthropic Trust grant RFP-12-03 (to A.B. and H.E.H.), and a Harvard Mind Brain Behavior Award and Harvard Brain Science Initiative Grant to H.E.H. C.D. and H.E.H. are investigators of the Howard Hughes Medical Institute.

Author information

Author notes

    • Shenqin Yao
    •  & Brant K. Peterson

    Present addresses: Allen Institute for Brain Science, Seattle, Washington 98103, USA (S.Y.); Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA (B.K.P.).

Affiliations

  1. Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA

    • Andres Bendesky
    • , Young-Mi Kwon
    • , Jean-Marc Lassance
    • , Caitlin L. Lewarch
    • , Shenqin Yao
    • , Brant K. Peterson
    • , Catherine Dulac
    •  & Hopi E. Hoekstra
  2. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Andres Bendesky
    • , Young-Mi Kwon
    • , Jean-Marc Lassance
    • , Brant K. Peterson
    •  & Hopi E. Hoekstra
  3. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Andres Bendesky
    • , Jean-Marc Lassance
    • , Caitlin L. Lewarch
    • , Shenqin Yao
    • , Catherine Dulac
    •  & Hopi E. Hoekstra
  4. Graduate Program in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA

    • Meng Xiao He
    •  & Hopi E. Hoekstra
  5. Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA

    • Catherine Dulac
    •  & Hopi E. Hoekstra
  6. Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Hopi E. Hoekstra

Authors

  1. Search for Andres Bendesky in:

  2. Search for Young-Mi Kwon in:

  3. Search for Jean-Marc Lassance in:

  4. Search for Caitlin L. Lewarch in:

  5. Search for Shenqin Yao in:

  6. Search for Brant K. Peterson in:

  7. Search for Meng Xiao He in:

  8. Search for Catherine Dulac in:

  9. Search for Hopi E. Hoekstra in:

Contributions

A.B. and H.E.H. conceived and designed the study. A.B. and Y.-M.K. collected and analysed behavioural data. A.B., Y.-M.K., and C.L.L. generated ddRAD-seq libraries. B.K.P. wrote code to map ddRAD-seq data. B.K.P. and A.B. wrote code to track animal behaviour from videos. A.B. and M.X.H. made a chromosome-level map of the Peromyscus genome. A.B. performed genetic mapping, pharmacology, and chemogenetics experiments. A.B. and J.-M.L. collected and analysed the RNA sequencing data. C.L.L. blind-scored behavioural assays. S.Y. made the Avp-Cre transgenic mice. A.B., Y.-M.K., J.-M.L., C.D., and H.E.H. analysed and interpreted results. A.B. and H.E.H. wrote the paper with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Hopi E. Hoekstra.

Reviewer Information Nature thanks S. Phelps and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains a Supplementary Discussion and Supplementary References.

Excel files

  1. 1.

    Supplementary Data 1

    This file contains genes within and up to 100 kb outside parental behaviour QTLs. Genes expressed at different levels in the hypothalamus of P. maniculatus and P. polionotus at a False Discovery Rate of 5% are shown. See Methods for details on the linear model. This file also indicates which genes in the QTLs have interspecific differences in protein sequence.

  2. 2.

    Supplementary Data 2

    This file contains a chromosome-level map of Peromyscus maniculatus bairdii (BW).

Videos

  1. 1.

    Parental behaviour of a Peromyscus polionotus father

    This video represents the typical behaviour of P. polionotus fathers.

  2. 2.

    Parental behaviour of a Peromyscus maniculatus father

    This video represents the typical behaviour of P. maniculatus fathers.

  3. 3.

    Parental behaviour of a Peromyscus polionotus mother

    This video represents the typical behaviour of P. polionotus mothers.

  4. 4.

    Parental behaviour of a Peromyscus maniculatus mother

    This video represents the typical behaviour of P. maniculatus mothers.

  5. 5.

    P. polionotus mother approaching a pup

    This video shows a short clip from Video 3.

  6. 6.

    P. polionotus father handling and licking a pup

    This video shows a short clip from Video 1.

  7. 7.

    P. maniculatus mother huddling a pup.

    This video shows a short clip from Video 4.

  8. 8.

    P. polionotus mother retrieving a pup

    This video shows a short clip from Video 3.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature22074

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.