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A Comparative Approach Shows Differences in Patterns of Numt Insertion During Hominoid Evolution

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Abstract

Nuclear integrations of mitochondrial DNA (numts) are widespread among eukaryotes, although their prevalence differs greatly among taxa. Most knowledge of numt evolution comes from analyses of whole-genome sequences of single species or, more recently, from genomic comparisons across vast phylogenetic distances. Here we employ a comparative approach using human and chimpanzee genome sequence data to infer differences in the patterns and processes underlying numt integrations. We identified 66 numts that have integrated into the chimpanzee nuclear genome since the human–chimp divergence, which is significantly greater than the 37 numts observed in humans. By comparing these closely related species, we accurately reconstructed the preintegration target site sequence and deduced nucleotide changes associated with numt integration. From >100 species-specific numts, we quantified the frequency of small insertions, deletions, duplications, and instances of microhomology. Most human and chimpanzee numt integrations were accompanied by microhomology and short indels of the kind typically observed in the nonhomologous end-joining pathway of DNA double-strand break repair. Human-specific numts have integrated into regions with a significant deficit of transposable elements; however, the same was not seen in chimpanzees. From a separate data set, we also found evidence for an apparent increase in the rate of numt insertions in the last common ancestor of humans and the great apes using a polymerase chain reaction–based screen. Last, phylogenetic analyses indicate that mitochondrial-numt alignments must be at least 500 bp, and preferably >1 kb in length, to accurately reconstruct hominoid phylogeny and recover the correct point of numt insertion.

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Acknowledgments

We are grateful to the National Institutes of Health for funding (Grant No. R15 GM073682-01 to N. M. Anthony). Additional funding came from the Bayer School of Natural and Environmental Sciences at Duquesne (to M. I. Jensen-Seaman and J. H. Wildschutte). We thank Charles Bell (University of New Orleans) for collaboration in the phylogenetic reconstructions. This manuscript has been substantially improved by thoughtful comments from two anonymous reviewers.

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Authors and Affiliations

  1. Department of Biological Sciences, Duquesne University, 600 Forbes Ave., Pittsburgh, PA, 15282, USA

    M. I. Jensen-Seaman & J. H. Wildschutte

  2. Department of Molecular Biology and Microbiology, Tufts University, 136 Harrison Ave., Boston, MA, 02111, USA

    J. H. Wildschutte

  3. Department of Biological Sciences, University of New Orleans, 2000 Lakeshore Drive, New Orleans, LA, 70148, USA

    I. D. Soto-Calderón & N. M. Anthony

  4. Biology Institute, University of Antioquia, AA. 1226, Medellin, Colombia

    I. D. Soto-Calderón

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  1. M. I. Jensen-Seaman
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  3. I. D. Soto-Calderón
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Correspondence to M. I. Jensen-Seaman.

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Jensen-Seaman, M.I., Wildschutte, J.H., Soto-Calderón, I.D. et al. A Comparative Approach Shows Differences in Patterns of Numt Insertion During Hominoid Evolution. J Mol Evol 68, 688–699 (2009). https://doi.org/10.1007/s00239-009-9243-4

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