The convergence of cytogenetics and rearrangement-based models for ancestral genome reconstruction

Froenicke et al. (2006) asked the question "Are molecular cytogenetics and bioinformatics suggesting diverging models of ancestral mammalian genomes?" Their commentary seems to imply that cytogenetics is superior to "bioinformatics" when it comes to studies of ancestral mammalian genomes. But, comparing cytogenetics with other approaches to deriving ancestral genomic architectures (like MGR developed by Bourque and Pevzner 2002) on two very different data sets (80+ cytogenetic maps vs. four distantly related sequenced genomes) does not say much about the merits and demerits of the approaches; instead, it indirectly evaluates the quality of the input data sets. In this context, the main conclusion of Froenicke et al. (2006) amounts to the statement that 80+ cytogenetic maps lead to a more definitive reconstruction than four divergent genomes when it comes to low-resolution ancestral architectures. We never argued against this point in our publications and even advocated for the use of radiation hybrid mapping (as a trade-off in resolution between cytogenetic and sequencing data) to extend the number of analyzed genomes (Murphy et al. 2003, 2005). Indeed, with more taxon sampling, a rearrangement-based reconstruction with just seven genomes (Murphy et al. 2005) is already highly consistent with the cytogenetics reconstruction. Before we substantiate this convergence, we clarify the notion of weak associations, which was used in Bourque et al. (2005) to alert the reader that some of the adjacencies were left as unresolved in the ancestor. The discrepancies identified by Froenicke et al. (2006) all involve weak associations and point toward a misunderstanding more than a contradiction. Finally, we underline some of the important strengths exclusive to rearrangement-based approaches, such as the ability to detect smaller genomic segments, to handle fast evolving lineages, and to orient conserved segments in the ancestors.