A Novel Gene Family NBPF: Intricate Structure Generated by Gene Duplications During Primate Evolution

Abstract

Partial and complete genome duplications occurred during evolution and resulted in the creation of new genes and gene families. We identified a novel and intricate human gene family located primarily in regions of segmental duplications on human chromosome 1. We named it NBPF, for neuroblastoma breakpoint family, because one of its members is disrupted by a chromosomal translocation in a neuroblastoma patient. The NBPF genes have a repetitive structure with high intragenic and intergenic sequence similarity in both coding and noncoding regions. These similarities might expose these genomic regions to illegitimate recombination, resulting in structural variation in the NBPF genes. The encoded proteins contain a highly conserved domain of unknown function, which we have named the NBPF repeat. In silico analysis combined with the isolation of multiple full-length cDNA clones showed that several members of this gene family are abundantly expressed in a large variety of tissues and cell lines. Strikingly, no discernable orthologues could be identified in the completed genomes of fruit fly, nematode, mouse, or rat, but sequences with low homology could be isolated from the draft canine and bovine genomes. Interestingly, this gene family shows primate-specific duplications that result in species-specific arrays of NBPF homologous sequences. Overall, this novel NBPF family reflects the continuous evolution of primate genomes that resulted in large physiological differences, and its potential role in this process is discussed.

The NBPF Gene Family

“…For instance, one third of primary neuroblastoma tumours carry a deletion of the 1p36 region (White et al, 2005). The NBPF genes have a repetitive structure with high intergenic and intragenic sequence similarity, both in coding and non-coding regions (Vinogradova et al, 2002;Vandepoele et al, 2005). The NBPF1 gene consists of 25 coding exons, but on the basis of their high sequence identities, these exons can be classified into 14 different exon types ( Figure 2B).…”

“…Several members of this gene family are abundantly expressed in different human cell lines and human tissues, but no discernable orthologs could be found in the genomes of mouse or rat. Nevertheless, the NBPF genes do not appear to be restricted to primates because sequences with low but significant homology to NBPF have been identified in bovine and canine genomes (Vandepoele et al, 2005). We previously analysed the genomic organisation of the NBPF gene family (Vandepoele et al, 2005).…”

“…Nevertheless, the NBPF genes do not appear to be restricted to primates because sequences with low but significant homology to NBPF have been identified in bovine and canine genomes (Vandepoele et al, 2005). We previously analysed the genomic organisation of the NBPF gene family (Vandepoele et al, 2005). For that analysis, we used the reference sequence of the human genome of the NCBI build 35, which is an improvement over the first release because it contains only 341 gaps (IHGSC 2004) instead of the 150,000 gaps that were present in the first draft version.…”

“…Frameshift and nonsense mutations in pseudogenes are indicated by asterisks. Three consecutive dots indicate the presence of gaps in the current genomic assembly (Updated from Vandepoele et al, 2005).…”

“…In addition to the 22 NBPF genes we identified before (Vandepoele et al, 2005), two additional NBPF genes are currently present in GenBank: NBPF23 and NBPF24. Copy number variations of NBPF23 were recently shown to be involved in neuroblastoma (see below) (Diskin et al, 2009).…”