Non-random genomic divergence in repetitive sequences of human and chimpanzee in genes of different functional categories

Abstract

Sequencing of the human and chimpanzee genomes has revealed ∼99% similarity in the coding sequence between both the species, which in no way parallels the observable phenotypic differences. Contribution of the non-coding sequences which comprise a bulk of the genome, in functional divergence between human and chimpanzee, is largely understudied. In this context, we have compared extents of divergence in the non-coding repetitive DNA in a data set of well-classified neuronal and housekeeping genes between human and chimpanzee. The coding regions of these genes have earlier been extensively compared between the two species. It was revealed that the neurodevelopmental genes show accelerated evolution compared to neurophysiology and housekeeping genes in human. In this study, comparative analysis in terms of repeat spectrum, divergence in dinucleotide content density, JC divergence and its partitioning in repeats versus unique regions and transcription factor binding sites indicate different extents of functional constraints associated with the non-coding repeat regions. The constraints are also different when the upstream and downstream genic regions are compared across the functional categories. The neurodevelopmental genes seem to diverge more in the genic regions, whereas the neurophysiology genes show higher divergence in the upstream 2 kb region. Most of the divergence observed in the housekeeping genes is contributed by repeats. We also observe an accumulation of function-specific transcription factor profiles in the human lineage. Interestingly, a major fraction of the regulatory sites in these regions is differently partitioned in the repetitive sequences which in turn is dependant upon the relative distribution of the repeats across the functional categories. Thus, differential distribution of repeats across the various functional categories could have substantial effects on genome wide regulation and structure. The insights obtained from this study further add a new facet to the contribution of non-coding factors especially repeats in divergence of human and chimpanzee.