Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

The initial name 'Neuroblastoma Breakpoint gene Family' (NBPF) was given because the first identified member of the family was found to be deleted in an individual with neuroblas- [4, 7] . The individual members of the Morpheus core duplicons are ordered according to location on chromosome 16 (left) . The mosaic structure of the complex duplication blocks is depicted on the right. The core duplicon part, which is shared by all duplication blocks, is marked by the red broken lines. Numbers next to the fragments refer to the start and end positions on the chromosome (in kb), and arrows indicate the relative orientation. Different colors refer to distinct duplication blocks, which are predicted based on reciprocal comparisons of each human subunit and its flanking sequence to outgroup mammalian genomes [4] . [19] . NBPF gene family members include variable numbers of tandemly repeated DUF1220 domains within their coding sequences. Since the name DUF1220 was initially a working designation assigned by the Pfam database curators, Sikela and van Roy [20] have proposed to rename the domain Olduvai. The different NBPF core duplicon genes are distributed along chromosome 1 in 16 copies, of which 6 are in tandem and 10 are dispersed [21] . The macaque genome has three copies of NBPF genes, while mice and other mammals have no clear orthologs. A possible ancestral gene is PDE4DIP, which includes a single Olduvai domain [22] . The Olduvai domain copy number has particularly expanded in humans. It increased from a single domain in mouse to 30-35 copies in new and old world monkeys and up to 300 domains in humans [22] . Based on sequence similarity, the domain structure of Olduvai can be divided into six primary subtypes including CON 1, 2 and 3 and HLS 1, 2 and mouse and includes other mammals. Functional properties of Olduvai, SPATA31 and TBC1D3, which have been studied in detail, and possible/predicted functions of other core duplicon gene families are included. CNV (median:variance) was extracted from a previous study [10] . * indicates CNV estimate based on number of Olduvai domains. # indicates CNV information for TRIM51 genes was extracted from a previous study [17] , and & indicates CNV for SPATA31 genes was extracted from a previous study [18] . and 3 [16, 22, 23] . The comparative analysis of Olduvai-domaincontaining NBPF genes in primates has shown that NBPF genes evolve under strong positive selection [13, 16] .