4.8 Article

Mutation and selection explain why many eukaryotic centromeric DNA sequences are often A plus T rich

Journal

NUCLEIC ACIDS RESEARCH
Volume 50, Issue 1, Pages 579-596

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab1219

Keywords

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Funding

  1. BBSRC [BB/K003356/1]
  2. Brazilian 'NottinghamBirmingham' PhD scheme by CAPES, Brazil
  3. Kurdistan Regional Government, Human Capacity Development Program
  4. National Institute of General Medical Sciences of the National Institutes of Health [R35GM119723]
  5. University of Nottingham
  6. OUP
  7. BBSRC [BB/K003356/1] Funding Source: UKRI

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The study found that A + T rich DNA can function as a centromere in the fission yeast Schizosaccharomyces pombe. Furthermore, the research suggests that the relative A + T content of centromeric DNA scales with the effective population size (N-e) across various animal, fungal, and yeast species. It is proposed that A + T rich DNA of almost any sequence can serve as a centromere in most Opisthokonta species, contributing to the rapid evolution of centromeric DNA.
We have used chromosome engineering to replace native centromeric DNA with different test sequences at native centromeres in two different strains of the fission yeast Schizosaccharomyces pombe and have discovered that A + T rich DNA, whether synthetic or of bacterial origin, will function as a centromere in this species. Using genome size as a surrogate for the inverse of effective population size (N-e) we also show that the relative A + T content of centromeric DNA scales with N-e across 43 animal, fungal and yeast (Opisthokonta) species. This suggests that in most of these species the A + T content of the centromeric DNA is determined by a balance between selection and mutation. Combining the experimental results and the evolutionary analyses allows us to conclude that A + T rich DNA of almost any sequence will function as a centromere in most Opisthokonta species. The fact that many G/C to A/T substitutions are unlikely to be selected against may contribute to the rapid evolution of centromeric DNA. We also show that a neo-centromere sequence is not simply a weak version of native centromeric DNA and suggest that neo-centromeres require factors either for their propagation or establishment in addition to those required by native centromeres.

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