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Widespread maintenance of genome heterozygosity in Schmidtea mediterranea

Nature Ecology & Evolution volume 1, Article number: 0019 (2017) Cite this article

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Abstract

Loss of heterozygosity through inbreeding or mitotic errors leads to reductions in progeny survival and fertility. Loss of heterozygosity is particularly exacerbated in geographically isolated populations, which are prone to inbreeding depression and faster rates of extinction. The regenerative capacities of the hermaphroditic biotype of the planarian Schmidtea mediterranea allowed us to perform a systematic genetic test of Mendelian segregation and study the loss of heterozygosity in the Spiralian superclade in general and planarians in particular. We discovered that ~300 Mb (~37.5%) of the genome retains heterozygosity even after ten generations of inbreeding, and show that these chromosomal regions have low diversity and recombination rates in wild populations. Our genetic and genomic analyses establish S. mediterranea as a genetically tractable system. The research also opens the door to study the evolutionary basis of non-Mendelian mechanisms, the adaptive advantages of chromosome structural heterozygotes and their potential relationship to the robust regenerative capacities of planarians.

The freshwater, free-living flatworm (platyhelminth) S. mediterranea has emerged as a powerful model system for studying adult stem cells and organ regeneration1,2. This species exists naturally as asexual and sexual reproductive diploid strains with four pairs of chromosomes, distinguishable by a chromosomal translocation that is only present in the asexual biotype3. Animals harbouring this translocation reproduce by transverse fission and do not differentiate germ lines or the somatic copulatory apparatus, whereas individuals lacking this translocation are hermaphroditic (Supplementary Fig. 1) and do not reproduce asexually. Although both biotypes display remarkable regenerative capacities, the ease of cultivation of the asexual S. mediterranea has generally favoured its study over the sexual biotype. Therefore, little is known about the mechanisms of heredity in this organism; genetic studies in free-living flatworms using microsatellite and ploidy measurements have been mostly limited to S. polychroa, a primarily parthenogenetic polyploid species4–8. Because the sexual S. mediterranea biotype can be found on the Mediterranean island of Sardinia, its natural history provides an additional opportunity to study the genetics of an animal that possesses robust regenerative capacities in the context of geographic isolation (see Supplementary Information). By developing the necessary culture conditions, we have taken advantage of the sexual S. mediterranea biotype to examine genome-wide Mendelian inheritance and genetic variability in planarians; this effort is not only the first such exploration in the Platyhelminthes, but also in the Lophotrochozoans/Spiralians, a molecularly understudied, species-rich animal superclade9.

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Figure 1: Sexual reproduction in S. mediterranea.
Figure 2: Nomenclature and inbreeding pedigree in a hermaphroditic, highly regenerative species (S. mediterranea).
Figure 3: Heterozygosity maintenance in the genomes of S2 and its lineages.
Figure 4: Suppression of loss of heterozygosity during sexual reproduction and mitosis.
Figure 5: Persistence of genome heterozygosity in wild populations from Sardinia.
Figure 6: J/V haplotypes and low recombination rates at non-MI SNPs in male/female gametes.

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Acknowledgements

The authors thank D. Chao, R. Krumlauf, K. Golic, S. Hawley, T. Piotrowski, E. Jorgensen and D. Grunwald for comments, discussions and suggestions during the preparation of this manuscript. We thank H. Li, J. Vallandingham and M. Gogol for help with data analysis and visualization. We are grateful to M. Pala for the original gift in 1999 of the sexual specimens of S. mediterranea and the Stowers Institute Planarian Core facility for skilful maintenance of our planarian colony. We acknowledge S.M.C. Robb and P. Reddien for the initial establishment of the S2 line, A. Rossi for the discussions and S. Sánchez-Piotrowski for his help in specimen collection. This work was funded in part by the National Institutes of Health (NIH R37GM057260) to A.S.A.

Author information

Authors and Affiliations

  1. Stowers Institute for Medical Research, Kansas City, 64110, Missouri, USA

    Longhua Guo, Shasha Zhang, Boris Rubinstein, Eric Ross & Alejandro Sánchez Alvarado

  2. Department of Neurobiology and Anatomy, Molecular Biology Program, University of Utah, Salt Lake City, 84112, Utah, USA

    Longhua Guo & Alejandro Sánchez Alvarado

  3. Howard Hughes Medical Institute, Stowers Institute for Medical Research, Kansas City, 64110, Missouri, USA

    Eric Ross & Alejandro Sánchez Alvarado

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  1. Longhua Guo
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Contributions

L.G. and A.S.A. conceived and designed the project. L.G. performed the experiments and data analysis. S.Z. helped with worm culture, crosses and genotyping. E.R. helped with identifying SNPs from the (S2F5b)F6b family. L.G. and B.R. developed algorithms to analyse Mendelian inheritance in small families and performed correlation analysis. L.G. developed figures. L.G. and A.S.A. interpreted the data and prepared the manuscript.

Corresponding author

Correspondence to Alejandro Sánchez Alvarado.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Note, Supplementary References, Supplementary Figures 1–9 (PDF 992 kb)

Supplementary Table 1

List of MI and non-MI SNPs identified (XLSX 1027 kb)

Supplementary Table 2

Probes used in the SNPtype dynamic array (XLSX 41 kb)

Supplementary Table 3

Genotyping Primers used in RFLP or PCR/Sanger sequencing (XLSX 39 kb)

Supplementary Table 4

Genotyping raw data (XLSX 63 kb)

Supplementary Video 1

The mating behavior in Schmidtea mediterranea (MP4 4553 kb)

Supplementary Video 2

The arrested single cells in D5D/D5I unhatched egg capsules were haploid oocytes (MP4 8211 kb)

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Guo, L., Zhang, S., Rubinstein, B. et al. Widespread maintenance of genome heterozygosity in Schmidtea mediterranea. Nat Ecol Evol 1, 0019 (2017). https://doi.org/10.1038/s41559-016-0019

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