Abstract
Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.
Highlights
Changes in primary DNA sequence that occur over evolutionary time alter transcription factor occupancy on DNA [1,2]
Gene dosage must be balanced largely because it is critical to maintain the stoichiometry of components of multi-protein complexes that are encoded at diverse locations throughout the genome
We report a new mechanism by which newly evolved X-chromosomes become dosage compensated in Diptera: the expansion of simple GA dinucleotide repeats increases the density of the conserved CLAMP zinc finger protein that recruits the dosage compensation complex to the X-chromosome
Summary
Changes in primary DNA sequence that occur over evolutionary time alter transcription factor occupancy on DNA [1,2]. Sex chromosome dosage compensation is a key model system with which to study this essential process because a large number of genes on a single chromosome are co-regulated to form a domain of coordinated gene expression [4,5]. Recent work demonstrated that the same mechanism of dosage compensation evolved independently across Dipterans, the diverged sex chromosomes are not all derived from the same ancient chromosome [6]. This conserved mechanism increases the transcript levels of all active genes along the length of the male X-chromosome two-fold to equalize gene expression between males (XY) and females (XX) [6,7]. It was hypothesized that these repeats promote targeting of the dosage compensation machinery to the X-chromosome [8], yet the mechanism remained unknown
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