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Title: A conserved genomic region between vertebrates and insects
P24
Danchin, Etienne G. J.; Abi-Rached, Laurent; Gilles, André; Pontarotti, Pierre

danchin@marseille.inserm.fr
INSERM, U119, 27 Bd Leï Roure, 13009 Marseille, France.

Identification of conserved regions between the genomes of distant species is a crucial step in the reconstruction of the genomic organization of their last common ancestor.
Here we decipher a conserved synteny between the human genome and the drosophila genome, as a result of a rigorous analysis that combines comparative genomics, phylogenetic analysis and statistical testing. All the previous studies that tried to investigate these questions were restrained by the lack of genomic data, that was unavailable until recently (such as the sequences of the human and drosophila genomes) or by inappropriate methods of analyses. We have identified 19 conserved genes between the human MHC (chr. 6p21.3) and paralogous (chr. 19p13, chr. 9q33, chr. 1q21-q25) regions; and a drosophila region of 2 Mb on chromosome I(X). This study represents a first step towards the reconstruction of the genome of Urbilateria (the ancestor of all bilaterian) and allows for a better understanding of the evolutionary history of our genome as well as other metazoan genomes.

Genome evolution entails changes in DNA sequences of coding and noncoding regions, in gene number and order along the chromosomes as well as in whole genome structure and organization. Comparisons between distant species' genomes allow us to reveal the evolutionary history of these genomes. On the one hand, the greater the distance between compared species, the farther back we can go in evolutionary history; however, on the other hand, the older speciation events are, the less information is available, and the more difficult it is to compare genomes. Identification of conserved syntenies (1) can reveal evolutionarily conserved blocks of genomes between species and may thus elucidate the ancestral organization of these portions of their genomes. To date, apart from the Hox cluster, which is conserved in all bilaterians (2), conserved syntenies have been found only in phyla that diverged relatively recently. The oldest other conserved syntenies described, thus far, are those found between vertebrates and cephalochordates (3). Descriptions of conserved syntenies between protostomes and deutorostomes have been claimed (4, 5) but these claims were neither supported by phylogenetic analysis nor sufficiently robust statistical testing and thus remain subjective.

Here we have tested whether conserved syntenies can be revealed between two members of distant phyla within metazoan (Fig. 1), the drosophila (protostomes) and the human (deuterostomes). Such conserved syntenies would provide a benchmark towards deciphering the -genomic organization of the last common ancestor of these two species : Urbilateria (6).
[1] Conserved syntenies are blocks of orthologous genes conserved between two species. Orthologous genes are two genes in two species which have arisen from a single ancestral gene and have been separated by a speciation event whereas paralogous genes are two genes that were separated by a duplication event in one species before speciation.
[2] A. Graham, N. Papalopulu, R. Krumlauf, Cell. 57, 367 (1989).
[3] L. Abi-Rached , A. Gilles, T. Shiina, P. Pontarotti, H. Inoko, Nature Genet. 31, (2002) in press.
[4] Z. Trachtulec, et al., Genomics. 44, 1 (1997).
[5] Z. Trachtulec , J. Forejt, Mamm Genome. 12, 227 (2001).
[6] E.M. DeRobertis, A. Sasai, Nature. 380, 37 (1996).cd