The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions,

The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions, all of which are characterized by the presence of interchromosomal segmental duplications. beta-satellites indicated that DUXY genes and beta-satellites evolved in concert. However, evolutionary forces acting on DUXY genes Rabbit polyclonal to PSMC3 may have induced amino acid sequence differences in the orthologous chimpanzee and human DUXY open reading frames (ORFs). The acquisition of complete ORFs in human copies might relate to evolutionary advantageous functions indicating neo-functionalization. We propose an evolutionary scenario in which an ancestral tandem array DUX gene cassette transposed to the hominoid Y chromosome followed by lineage-specific chromosomal rearrangements 1194044-20-6 paved the way for a species-specific evolution of the Y-chromosomal members of a large highly diverged homeobox gene family. Introduction Among human chromosomes the Y chromosome shows the highest proportion of segmental duplications [1]C[3], a class of low-copy repeats 1194044-20-6 implicated in the large-scale variation of the human genome [4]. Such duplicated sequences are found interspersed throughout the genome, however they predominantly tend to cluster in pericentromeric and subtelomeric regions [4]C[6]. Not surprisingly all four Y-chromosomal euchromatin/heterochromatin transition regions are composed of duplicated sequences [7], [8]. Within the Yq11.1/Yq11.21 transition region a specific genomic segment of 30 kb is framed by segmental duplications, but presents distinctive differences to its direct genomic environment. This segment is characterized by the presence of an imperfectly organized tandem-repeat structure encoding members of the DUX gene family [8]. Recurrent alternating repeat elements of the LSAU and 68 bp beta-satellite repeat family form a scaffold in which the DUX genes are embedded. Length variations of the tandem repeat are exclusively restricted to the beta-satellite regions. This basic structure is highly similar to the architectural features of the D4Z4 tandem array, a 3.3 kb repeat unit located in highly variable numbers in 4q35 [9], [10]. The polymorphic repeat also encodes a member of the DUX gene family [11], [12] termed which is supposed to have a major impact on the etiology of FSHD (Facioscapulohumeral muscular dystrophy;[13]C[15]), the third most common muscular dystrophy [16]. Although a similar tandem array exists in 10q26, no association with FSHD could be established [17]C[19]. Additional copies of the DUX gene family with nucleotide sequence identities ranging from 80C99% are scattered throughout the heterochromatic regions of the short arms of all acrocentric chromosomes and chromosomal bands 1q12, 9q12, and 10cen [10]. Due to their 1194044-20-6 unusual organization and chromosomal distribution pattern DUX-containing repeats reflect a specific category of segmental duplications. Recently, strong evidence has been provided that the DUX4 open reading frame is evolutionarily conserved. Homologues were identified in the genomes of rodents, Afrotheria and several other species. Moreover, phylogenetic analysis discloses the descent of the primate and Afrotherian orthologs from a retrotransposed copy of an intron-containing DUX gene [20]. Although this study profited from the extensive whole-genome sequence data, no proof was provided of the existence of Y-chromosomal DUX copies in non-human primates. This can be easily explained by the obvious preference for female individuals in such efforts. Here we focus on the evolutionary history of DUX genes on the primate Y chromosomes. The date of initial appearance of Y-chromosomal DUX copies is documented and species-specific varying Y-chromosomal localizations are identified. Furthermore, the autosomal distribution pattern of DUXY-related genes provides evidence for their enormous increase in dispersal and amplification in the higher primate genome. Detailed comparative analysis of the human and common chimpanzee DUXY locus allowed us to infer 1194044-20-6 the evolutionary processes shaping its basic structural organization. Results Cosmid contig of the human DUXY locus By filter hybridization of the human Y chromosome-specific cosmid library LL0YNC03M we identified 1194044-20-6 36 DUXY-positive cosmid clones, of which 22 were further analyzed. Using the NcoI restriction map.

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