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MBE Advance Access published online on July 28, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg202
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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Accepted June 16, 2003
© 2003 Society for Molecular Biology and Evolution

Original Articles

pANT: A Method for the Pairwise Assessment of Nonfunctionalization Times of Processed Pseudogenes

Sarel J. Fleishman 1, Tal Dagan 2*, and Dan Graur 2

1 Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv 69978, Israel
2 Department of Zoology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv 69978, Israel

* To whom correspondence should be addressed. E-mail: tali{at}kimura.tau.ac.il.


  Abstract

We present a method for pairwise Assessment of Nonfunctionalization Times (pANT) in processed pseudogenes. Contrary to existing methods for estimating nonfunctionalization times, pANT utilizes previously calculated probabilities of nucleotide substitution as explicit rate measurements, rather than assume that the substitution rates are the same for all nucleotides. Thus the method allows a more accurate computation of the time that has elapsed since the nonfunctionalization of a pseudogene. Whereas existing methods require the sequence of an orthologous functional gene, which is not always at hand, pANT only uses the pairwise alignment of the gene/pseudogene pair, thus expanding the range of problems that can be tackled. In order to estimate evolutionary times in nonfunctional sequences, pANT measures the differences in the pairwise alignment of a gene and its paralogous processed pseudogene using only the first and second codon positions. It assumes that due to functional constraints, these positions in the sequence of the functional homologue have not changed since the time of nonfunctionalization of the pseudogene. Hence, the sequence of the gene may be used as the ancestor of the pseudogene. We show that due to the method's reliance on a detailed substitution matrix, which is derived separately for each species, it is more accurate than existing methods. We applied pANT to the case of the unitary {alpha}-1,3-galactosyltransferase human pseudogene, and found that our estimate of the nonfunctionalization time was in agreement with that obtained by taxonomic and paleontological considerations pertaining to the divergence between platyrrhines (New-World monkeys) and cattarhines (Old-World monkeys).

Key Words: Molecular evolution, substitution rates, pseudogenes, nonfunctionalization, computational method, galactosyltransferase


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