Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus.

Abstract

In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous within each species but differs somewhat between species. Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages. The data suggest that the U2 tandem repeat, once established in the primate lineage, contained sequence elements favoring perpetuation and concerted evolution of the array in situ, despite a pericentric inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon and other Old World monkeys with the 6 kb U2 repeat unit in humans and other hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a 5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of the provirus by homologous recombination between the LTRs generated a 6 kb U2 repeat unit containing a solo LTR. Remarkably, both junctions between the human U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR sequence, suggesting a role for the LTR in the origin or maintenance of the primate U2 array.

Changing transcription start sites in H‐type α(1,2)fucosyltransferase Gene (FUT1) during differentiation of the human erythroid lineage

“…In addition, the 5′ flanking region of exon 2 (intron 1) was examined by the basic local alignment search tool (BLAST) (http://www.ncbi.nlm.nih.gov/BLAST/). The 5′ flanking region of exon 2 has a high degree of DNA sequence similarity with a long terminal repeat from a putative human endogenous retrovirus in U2 snRNA locus (LTR13, accession number L37793, GenBank) [24] at positions Ϫ1114 to 149 bp (following the notation of the transcription start site of the exon 2 as ϩ1), an Alu sequence (inserted in LTR13-like sequence) at positions Ϫ514 to Ϫ232 bp and repeats of a human 37-bp minisatellite specific to chromosome 19 (accession number K03500, GenBank) [25] at the position Ϫ1650 to Ϫ1231 bp ( Fig. 2A).…”

The Microsatellite Sequence (CT)n · (GA)nPromotes Stable Chromosomal Integration of Large Tandem Arrays of Functional Human U2 Small Nuclear RNA Genes

“…As discussed in Results, failure of BamHI to cut artificial arrays confirms the absence of tail-to-tail junctions. The BamHI digests were resolved by field inversion gel electrophoresis (FIGE), and the dried agarose gel was probed with the mU2 repeat unit as described elsewhere (49).…”

“…In primates, the genes encoding U2 small nuclear RNA (U2 snRNA) are organized as a nearly perfect tandem array at a single chromosomal locus designated RNU2 (40,49,58,64). The number of repeat units within an array can range from 5 to 25, but this number is heritable and somatically stable (33,49).…”

“…The number of repeat units within an array can range from 5 to 25, but this number is heritable and somatically stable (33,49). In humans, the 6.1-kb U2 repeat unit contains the 188-bp U2 snRNA coding region, a solo retroviral long terminal repeat, two Alu elements, a 3Ј truncated L1 LINE element, and an imperfect d(CT) n ⅐ d(GA) n microsatellite sequence (n Ϸ 70) located about 300 bp downstream of the U2 coding region (49). Of these identified sequence elements, only the U2 snRNA gene is known to have a function.…”

“…One candidate recombinogenic element is the CT microsatellite. The CT microsatellite (n Ϸ 70) in the tandemly repeated U2 genes is located 0.3 kb downstream from the U2 coding region (28,49); a similar CT microsatellite (n Ϸ 15 to 25) is also located about 1.8 kb downstream from the U1 snRNA coding region in the tandemly repeated human U1 genes (27,38); a GT microsatellite (n ϭ 36) is located 1.4 kb downstream (0.3 kb upstream) from the 5S rRNA transcription unit (35,51); and a GT microsatellite (n ϭ 29) is found downstream from the putative transcription terminator for 45S rRNA (13). The CT microsatellite in the U2 snRNA repeat units is well conserved from baboons to humans, despite some length polymorphism (33).…”