Barbara Poszewiecka1, Krzysztof Gogolewski2, Paweł Stankiewicz3, Anna Gambin2. 1. Institute of Informatics, Warsaw University, Warsaw, Poland. b.poszewiecka@mimuw.edu.pl. 2. Institute of Informatics, Warsaw University, Warsaw, Poland. 3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, US.
Abstract
BACKGROUND: The reduction of the chromosome number from 48 in the Great Apes to 46 in modern humans is thought to result from the end-to-end fusion of two ancestral non-human primate chromosomes forming the human chromosome 2 (HSA2). Genomic signatures of this event are the presence of inverted telomeric repeats at the HSA2 fusion site and a block of degenerate satellite sequences that mark the remnants of the ancestral centromere. It has been estimated that this fusion arose up to 4.5 million years ago (Mya). RESULTS: We have developed an enhanced algorithm for the detection and efficient counting of the locally over-represented weak-to-strong (AT to GC) substitutions. By analyzing the enrichment of these substitutions around the fusion site of HSA2 we estimated its formation time at 0.9 Mya with a 95% confidence interval of 0.4-1.5 Mya. Additionally, based on the statistics derived from our algorithm, we have reconstructed the evolutionary distances among the Great Apes (Hominoidea). CONCLUSIONS: Our results shed light on the HSA2 fusion formation and provide a novel computational alternative for the estimation of the speciation chronology.
BACKGROUND: The reduction of the chromosome number from 48 in the Great Apes to 46 in modern humans is thought to result from the end-to-end fusion of two ancestral non-human primate chromosomes forming the human chromosome 2 (HSA2). Genomic signatures of this event are the presence of inverted telomeric repeats at the HSA2 fusion site and a block of degenerate satellite sequences that mark the remnants of the ancestral centromere. It has been estimated that this fusion arose up to 4.5 million years ago (Mya). RESULTS: We have developed an enhanced algorithm for the detection and efficient counting of the locally over-represented weak-to-strong (AT to GC) substitutions. By analyzing the enrichment of these substitutions around the fusion site of HSA2 we estimated its formation time at 0.9 Mya with a 95% confidence interval of 0.4-1.5 Mya. Additionally, based on the statistics derived from our algorithm, we have reconstructed the evolutionary distances among the Great Apes (Hominoidea). CONCLUSIONS: Our results shed light on the HSA2 fusion formation and provide a novel computational alternative for the estimation of the speciation chronology.
Authors: Ze Cheng; Mario Ventura; Xinwei She; Philipp Khaitovich; Tina Graves; Kazutoyo Osoegawa; Deanna Church; Pieter DeJong; Richard K Wilson; Svante Pääbo; Mariano Rocchi; Evan E Eichler Journal: Nature Date: 2005-09-01 Impact factor: 49.962