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Methods

Indel-Based Evolutionary Distance and Mouse–Human Divergence

¹ National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20892, USA ² Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

We propose a method for estimating the evolutionary distance between DNA sequences in terms of insertions and deletions (indels), defined as the per site number of indels accumulated in the course of divergence of the two sequences. We derive a maximal likelihood estimate of this distance from differences between lengths of orthologous introns or other segments of sequences delimited by conservative markers. When indels accumulate, lengths of orthologous introns diverge only slightly slower than linearly, because long indels occur with substantial frequencies. Thus, saturation is not a major obstacle for estimating indel-based evolutionary distance. For introns of medium lengths, our method recovers the known evolutionary distance between rat and mouse, 0.014 indels per site, with good precision. We estimate that mouse–human divergence exceeds rat–mouse divergence by a factor of 4, so that mouse–human evolutionary distance in terms of selectively neutral indels is 0.056. Because in mammals, indels are 14 times less frequent than nucleotide substitutions, mouse–human evolutionary distance in terms of selectively neutral substitutions is 0.8.

³ Corresponding author.
E-MAIL kondrashov{at}ncbi.nlm.nih.gov; FAX (301) 480-2290.

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