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FUNCTIONAL GENOMICS

Ultraconservation of enhancers is not ultranecessary

Nature Genetics volume 53, pages 429–430 (2021)Cite this article

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Stretches of non-coding DNA that have remained identical across millions of years of evolution are typically assumed to have functional regulatory roles that would be compromised by any amount of nucleotide substitution. A new study finds that these ultraconserved regions are more robust to mutagenesis than their level of conservation would suggest.

As organisms reproduce, mistakes in DNA replication create novel mutations. Most of these changes are neutral, meaning they are tolerated, and a small percentage of them persist just by chance. In contrast, deleterious mutations that decrease an organism’s likelihood of surviving and reproducing are much less likely to persist in the gene pool, owing to a process known as purifying selection1,2. Regions of the genome that are necessary for embryonic development exemplify this phenomenon. They are often conserved, meaning that they are devoid of DNA substitutions even across huge evolutionary timescales, thus suggesting that every nucleotide is necessary, and any mutations would disrupt their function. A new study from Snetkova et al.3 challenges this idea.

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Fig. 1: Diagram of a transgenic mouse embryo at embryonic day 11.5 (akin to those examined by Snetkova et al.).

References

  1. Siepel, A. et al. Genome Res 15, 1034–1050 (2005).

    Article  CAS  Google Scholar 

  2. Zoonomia Consortium. Nature 587, 240–245 (2020).

    Article  CAS  Google Scholar 

  3. Snetkova, V. et al. Nat. Genet. https://doi.org/10.1038/s41588-021-00812-3 (2021).

  4. Levine, M. Curr. Biol. 20, R754–R763 (2010).

    Article  CAS  Google Scholar 

  5. Osterwalder, M. et al. Nature 554, 239–243 (2018).

    Article  CAS  Google Scholar 

  6. Kryukov, G. V., Schmidt, S. & Sunyaev, S. Hum. Mol. Genet. 14, 2221–2229 (2005).

    Article  CAS  Google Scholar 

  7. Bejerano, G. et al. Science 304, 1321–1325 (2004).

    Article  CAS  Google Scholar 

  8. Townsley, K. G., Brennand, K. J. & Huckins, L. M. Nat. Neurosci. 23, 1509–1521 (2020).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. University of California, San Francisco, San Francisco, CA, USA

    Maureen Pittman & Katherine S. Pollard

  2. Gladstone Institute of Data Science & Biotechnology, San Francisco, CA, USA

    Maureen Pittman & Katherine S. Pollard

  3. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Katherine S. Pollard

Authors
  1. Maureen Pittman
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  2. Katherine S. Pollard
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Correspondence to Katherine S. Pollard.

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The authors declare no competing interests.

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Pittman, M., Pollard, K.S. Ultraconservation of enhancers is not ultranecessary. Nat Genet 53, 429–430 (2021). https://doi.org/10.1038/s41588-021-00839-6

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  • DOI: https://doi.org/10.1038/s41588-021-00839-6

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