Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Matters Arising
  • Published:

Limitations of gamete sequencing for crossover analysis

Nature volume 606, pages E1–E3 (2022)Cite this article

Subjects

The Original Article was published on 03 June 2020

arising from A. D. Bell et al. Nature https://doi.org/10.1038/s41586-020-2347-0 (2020)

Using single-cell whole-genome sequencing to identify crossover locations along chromosomes in a large number of human sperm cells, Bell et al.1 find that, in cells and individuals with higher numbers of crossovers, those crossovers tend to be closer together and more centrally distributed along the genomic (megabase) lengths of the chromosomes. They conclude that a global, nucleus-wide factor coordinates crossover number, spacing and location, and that this factor varies across individuals. Here we show that a control experiment used by Bell et al. to support this conclusion is invalid, because they analyse gametes, which inherit only a subset of the crossovers that formed in prophase meiocytes, and they use a genomic (megabase) metric for inter-crossover distances, when these are in fact determined according to physical (micrometre) distance along prophase chromosome axes. The flaw in the analysis of Bell et al. highlights intrinsic limitations of using gamete sequence data to understand crossover patterning.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Transmission of crossover crowding from bivalent chromosomes to two-crossover gametic chromosomes.

References

  1. Bell, A. D. et al. Insights into variation in meiosis from 31,228 human sperm genomes. Nature 583, 259–264 (2020).

    Article  ADS  CAS  Google Scholar 

  2. Codina-Pascual, M. et al. Crossover frequency and synaptonemal complex length: their variability and effects on human male meiosis. Mol. Hum. Reprod. 12, 123–133 (2006).

    Article  CAS  Google Scholar 

  3. Kleckner, N., Storlazzi, A. & Zickler, D. Coordinate variation in meiotic pachytene SC length and total crossover/chiasma frequency under conditions of constant DNA length. Trends Genet. 19, 623–628 (2003).

    Article  CAS  Google Scholar 

  4. Wang, S. et al. Inefficient crossover maturation underlies elevated aneuploidy in human female meiosis. Cell 168, 977–989 (2017).

    Article  CAS  Google Scholar 

  5. Wang, S. et al. Per-nucleus crossover covariation and implications for evolution. Cell 177, 326–338 (2019).

    Article  CAS  Google Scholar 

  6. Wang, Y. et al. ESA1 regulates meiotic chromosome axis and crossover frequency via acetylating histone H4. Nucleic Acids Res. 49, 9353–9373 (2021).

    Article  CAS  Google Scholar 

  7. Wang, R. J., Dumont, B. L., Jing, P. & Payseur, B. A. A first genetic portrait of synaptonemal complex variation. PLoS Genet. 15, e1008337 (2019).

    Article  CAS  Google Scholar 

  8. Halldorsson, B. V. et al. Characterizing mutagenic effects of recombination through a sequence-level genetic map. Science 363, eaau1043 (2019).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Evolution and Ecology, University of California, Davis, CA, USA

    Carl Veller

  2. Center for Population Biology, University of California, Davis, CA, USA

    Carl Veller

  3. Center for Reproductive Medicine, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Key Laboratory of Reproductive Endocrinology of Ministry of Education, Jinan, China

    Shunxin Wang & Liangran Zhang

  4. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette Cedex, France

    Denise Zickler

  5. Advanced Medical Research Institute, Shandong University, Jinan, China

    Liangran Zhang

  6. State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China

    Liangran Zhang

  7. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA

    Nancy Kleckner

Authors
  1. Carl Veller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunxin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denise Zickler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liangran Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nancy Kleckner
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to writing the manuscript.

Corresponding authors

Correspondence to Carl Veller or Nancy Kleckner.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Veller, C., Wang, S., Zickler, D. et al. Limitations of gamete sequencing for crossover analysis. Nature 606, E1–E3 (2022). https://doi.org/10.1038/s41586-022-04693-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41586-022-04693-2

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing