Reconstructing Ancient DNA Sequences in Silico


The increasing number of mammalian genome sequences becoming available provides scientists with dramatic opportunities to computationally reconstruct ancestral mammalian genomic sequences by comparing the genomes of living descendants. In this article, we review computational genome reconstruction methods in different scales, from baseā€level reconstruction to chromosomal rearrangement reconstruction.

Keywords: genome reconstruction; substitution; insertion and deletion; rearrangement

Figure 1.

The position of boreoeutherian common ancestor.

Figure 2.

A reconstructed region based on seven descendant species using armadillo and elephant as outgroups. The reconstructed ancestral sequences, including boreoeutherian, euarchontoglires, primate ancestor, ape ancestor, are shown above the multiple alignment. Position (1) is an ape‐specific deletion. Position (2) corresponds to two deletion events in primate and rodent, respectively. Position (3) is a substitution happened before euarchontoglires ancestor.

Figure 3.

A microinversion happened on the branch leading from the boreoeutherian common ancestor to the euarchontoglires common ancestor (the primate–rodent ancestor). The corresponding human region is hg18.chr13:57 380 591–57 383 765. This snapshot from University of California at Santa Cruz (UCSC) genome browser clearly shows the relative orientations from which the ancestral orientation can be inferred by parsimony.



Blanchette M (2007) Computation and analysis of genomic multi‐sequence alignments. Annual Review of Genomics and Human Genetics 8: 193–213.

Blanchette M, Green ED, Miller W and Haussler D (2004) Reconstructing large regions of an ancestral mammalian genome in silico. Genome Research 14: 2412–2423.

Bourque G, Pevzner PA and Tesler G (2004) Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. Genome Research 14: 507–516.

Bourque G, Tesler G and Pevzner PA (2006) The convergence of cytogenetics and rearrangement‐based models for ancestral genome reconstruction. Genome Research 16: 311–313.

Bourque G, Zdobnov EM, Bork P, Pevzner PA and Tesler G (2005) Comparative architectures of mammalian and chicken genomes reveal highly variable rates of genomic rearrangements across different lineages. Genome Research 15: 98–110.

Diallo AB, Makarenkov V and Blanchette M (2007) Exact and heuristic algorithms for the Indel Maximum Likelihood Problem. Journal of Computational Biology 14: 446–461.

Felsenstein J (2004) Inferring phylogenies. Sunderland, MA: Sinauer Associates.

Froenicke L, Caldes MG, Graphodatsky A et al. (2006) Are molecular cytogenetics and bioinformatics suggesting diverging models of ancestral mammalian genomes? Genome Research 16: 306–310.

Gibbs RA, Rogers J, Katze MG et al. (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316: 222–234.

Hannenhalli S and Pevzner PA (1999) Transforming cabbage into turnip: polynomial algorithm for sorting signed permutations by reversals. Journal of the ACM 46: 1–27.

Kent WJ, Baertsch R, Hinrichs A, Miller W and Haussler D (2003) Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proceedings of the National Academy of Sciences of the USA 100: 11484–11489.

Kim J and Sinha S (2007) Indelign: a probabilistic framework for annotation of insertions and deletions in a multiple alignment. Bioinformatics 23: 289–297.

Koshi JM and Goldstein RA (1996) Probabilistic reconstruction of ancestral protein sequences. Journal of Molecular Evolution 42: 313–320.

Lucena B and Haussler D (2005) Counterexample to a claim about the reconstruction of ancestral character states. Systematic Biology 54: 693–695.

Ma J, Zhang L, Suh BB et al. (2006) Reconstructing contiguous regions of an ancestral genome. Genome Research 16: 1557–1565.

Margulies EH, Vinson JP, Miller W et al. (2005) An initial strategy for the systematic identification of functional elements in the human genome by low‐redundancy comparative sequencing. Proceedings of the National Academy of Sciences of the USA 102: 4795–4800.

Mikkelsen TS, Wakefield MJ, Aken B et al. (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non‐coding sequences. Nature 447: 167–177.

Murphy WJ, Larkin DM, Everts‐van der A et al. (2005) Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309: 613–617.

Nadeau JH and Taylor BA (1984) Lengths of chromosomal segments conserved since divergence of man and mouse. Proceedings of the National Academy of Sciences of the USA – Biological Sciences 81: 814–818.

Pevzner P and Tesler G (2003) Genome rearrangements in mammalian evolution: lessons from human and mouse genomes. Genome Research 13: 37–45.

Rocchi M, Archidiacono N and Stanyon R (2006) Ancestral genomes reconstruction: an integrated, multi‐disciplinary approach is needed. Genome Research 16: 1441–1444.

Sankoff D, Leduc G, Antoine N et al. (1992) Gene order comparisons for phylogenetic inference: evolution of the mitochondrial genome. Proceedings of the National Academy of Sciences of the USA 89: 6575–6579.

Sankoff D and Nadeau JH (2003) Chromosome rearrangements in evolution: from gene order to genome sequence and back. Proceedings of the National Academy of Sciences of the USA 100: 11188–11189.

Schultz TR and Churchill GA (1999) The role of subjectivity in reconstructing ancestral character states: a Bayesian approach to unknown rates, states, and transformation asymmetries. Systematic Biology 48: 651–664.

Wienberg J (2004) The evolution of eutherian chromosomes. Current Opinion in Genetics and Development 14: 657–666.

Yang ZH, Kumar S and Nei M (1995) A new method of inference of ancestral nucleotide and amino‐acid‐sequences. Genetics 141: 1641–1650.

Zhang JZ and Nei M (1997) Accuracies of ancestral amino acid sequences inferred by the parsimony, likelihood, and distance methods. Journal of Molecular Evolution 44: S139–S146.

Further Reading

Liberles DA (2007) Ancestral Sequence Reconstruction. Oxford: Oxford University Press.

Pevzner PA (2000) Computational Molecular Biology: An Algorithmic Approach. Cambridge, MA: The MIT Press.

Web Links UCSC genome browser, including sequences and alignments. MGR, multiple genome rearrangements analysis. CARs, partitioning genomes into synteny blocks and reconstructs ancestral order of them; TBA, multiple sequence alignment program. Evolutionary Highway, genome structure visualization for multiple species.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Ma, Jian(Mar 2008) Reconstructing Ancient DNA Sequences in Silico. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020736]