Human Paralogs of KIAA0187 Were Created through Independent Pericentromeric-Directed and Chromosome-Specific Duplication Mechanisms

Abstract

KIAA0187 is a gene of unknown function that maps to 10q11 and has been subject to recent duplication events. Here we analyze 18 human paralogs of this gene and show that paralogs of exons 14-23 were formed through satellite-associated pericentromeric-directed duplication, whereas paralogs of exons 1-9 were created via chromosome-specific satellite-independent duplications. In silico, Northern, and RT-PCR analyses indicate that nine paralogs are transcribed, including four in which KIAA0187 exons are spliced onto novel sequences. Despite this, no new genes appear to have been created by these events. The chromosome 10 paralogs map to 10q11, 10q22, 10q23.1, and 10q23.3, forming part of a complex family of chromosome-specific repeats that includes GLUD1, Cathepsin L, and KIAA1099 pseudogenes. Phylogenetic analyses and comparative FISH indicates that the 10q23.1 and 10q23.3 repeats were created in 10q11 and relocated by a paracentric inversion 13 to 27 Myr ago. Furthermore, the most recent duplications, involving the KIAA1099 pseudogenes, have largely been confined to 10q11. These results indicate a simple model for the evolution of this repeat family, involving multiple rounds of centromere-proximal duplication and dispersal through intrachromosomal rearrangement. However, more complex events must be invoked to account for high sequence identity between some paralogs.

Punctuated duplication seeding events during the evolution of human chromosome 2p11

“…Previous analyses have suggested that pericentromeric regions have been formed via the duplication of euchromatic segments that have colonized pericentromeric DNA over the past 30 Myr of evolution (Eichler et al 1996;Jackson et al 1999;Horvath et al 2000bHorvath et al , 2003Bailey et al 2002;Crosier et al 2002;She et al 2004a;Locke et al 2005). This duplicative transposition of euchromatic segments into pericentromeric regions (which we have termed "pericentromeric seeding") has led to the formation of complex mosaics of segmental duplications consisting of juxtaposed duplicons from diverse euchromatic positions.…”

“…Limited comparisons of pericentromeric regions among closely related primates suggest extraordinary dynamism where duplication, deletion, and rearrangement of large segments of DNA occur at an unprecedented scale (Eichler et al 1996(Eichler et al , 1997Regnier et al 1997;Zimonjic et al 1997;Orti et al 1998;Horvath et al 2000bHorvath et al , 2003Crosier et al 2002). These findings have suggested that the actual number of "chromosomal rearrangements" among primates far exceed expectations based on the comparison of primate karyotypes.…”

Genomic Sequence and Transcriptional Profile of the Boundary Between Pericentromeric Satellites and Genes on Human Chromosome Arm 10p

“…None of the other four annotated genes proximal of satellites, ap000526.1 and ap000523.c22.4 on 22q11, and FRGL and c20orf91 on 20q11, are known genes. Ap000526.1 is a paralogous fragment of the KIAA0187 gene defined by a single spliced EST from testis, AA725634 (Dunham et al 1999;Crosier et al 2002). Ap000523.c22.4 is defined as a gene on the basis of a single 2792bp cDNA also derived from testis which has nine mismatches with the chromosome 22 sequence.…”

Segmental Duplications in Euchromatic Regions of Human Chromosome 5: A Source of Evolutionary Instability and Transcriptional Innovation

“…Viale and C. Ortola, unpubl.). Such a clustering of recent transcribed pseudogenes in duplicated genomic regions is reminiscent of the characteristics of primate-specific segmental duplications (Bailey et al 2002b;Crosier et al 2002) and raise questions about when these sequences have arisen, how they were maintained, and the role that they may have played in chromosome and genome evolution.…”