Reconstructing the Phylogeny of the Human Chromosome 4 Synteny using Comparative Karyology and Genomic Data Analysis

Abstract

This work focuses on the evolution of the architecture of human chromosome 4 (HSA4) through the analysis of chromosomal regions that have been conserved over time, and the comparison of regions that have been involved in different rearrangements in placental lineages. As with most elements of the human genome, HSA4 is considered to be evolutionarily stable. A more detailed analysis indicates that the syntenic association has been reshuffled by a series of rearrangements, yielding different chromosomes in various taxa. In its ancestral eutherian state, HSA4 has a syntenic association with HSA8p. We investigated the complex origin of this human chromosome using three different approaches, including: the analysis of chromosome painting features among 157 mammalian species gleaned from published data; the analysis of conserved syntenic orthologous blocks derived from the Ensembl dataset (www.ensembl.org); and the reconstruction of the orthologues of HSA4 in various species, using a maximum parsimony (MP) analysis of evolutionary breakpoints. The phylogenetic pattern recovered shows four discrete chromosomal regions have primarily been implicated in chromosomal rearrangement: 4p15.3, 4p16.1, 4q12 and 4q31.1. Our results demonstrate that chromosome painting and ancestral chromosome reconstructions can elucidate the diverse structural rearrangements that characterize different evolutionary lineages.

Key words:

• comparative chromosome painting
• comparative genomics
• evolutionary breakpoints
• human evolution