Bosch, N. et al. Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events. Hum. Mol. Genet. 16, 2572-2582

Genes and Disease Program, Center for Genomic Regulation (CRG-UPF) and CIBERESP, Barcelona, Catalonia, Spain.
Human Molecular Genetics (Impact Factor: 6.39). 12/2007; 16(21):2572-82. DOI: 10.1093/hmg/ddm209
Source: PubMed


Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs), termed REPD and REPP, that mediate different kinds of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated with 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here, we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region plus a single member on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5'-untranslated region sequences, but both share the same open reading frame and are ubiquitously expressed. Sequence analysis and comparative fluorescence in situ hybridization studies showed that FAM90A subfamily II suffered a big expansion in the hominoid lineage, whereas subfamily I members were likely generated sometime around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.

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    • "Moreover, a substantial number of studies have shown that new genes can also arise through retroposition, an RNA-based duplication mechanism (Kaessmann et al. 2009; Kaessmann 2010; Zhang 2013). Collectively, these genomic changes resulted in a large number of primate-specific genes or expansions of gene families (Vandepoele et al. 2005; Bosch et al. 2007; Andres et al. 2008; Wainszelbaum et al. 2008; Das et al. 2010; Arroyo et al. 2012; Dennis et al. 2012; Giannuzzi et al. 2013), some of which are reported to be related to phenotypic traits (Das et al. 2010), highlighting their important role in primate evolution. "
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    ABSTRACT: Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.
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    • "Furthermore, the DEF cluster b is embedded in one of two complex segmental duplications, REPD and REPP, involved in polymorphic inversions [1-3]. Recently, in these regions also CNV for the FAM90A gene class was shown [4]. Due to this repetitive structure which is refractory to analysis, the locus is one of the few regions with a remaining recalcitrant gap even in the most recent human genome assembly GRCh37 (hg19, February 2009). "
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    ABSTRACT: Copy number variation (CNV) in the range from 2 to 12 per diploid genome is an outstanding feature of the beta-defensin gene (DEFB) cluster on human chromosome 8p23.1 numerously demonstrated by different methods. So far, CNV was proven for a 115 kb region between DEFB4 and 21 kb proximal of DEFB107 but the borders for the entire CNV repeat unit are still unknown. Our study aimed to narrow down the distal border of the DEFB cluster. We established tests for length polymorphisms based on amplification and capillary electrophoresis with laser-induced fluorescence (CE-LIF) analysis of seven insertion/deletion (indel) containing regions spread over the entire cluster. The tests were carried out with 25 genomic DNAs with different previously determined cluster copy numbers. CNV was demonstrated for six indels between ~1 kb distal of DEFB108P and 10 kb proximal of DEFB107. In contrast, the most distal indel is not affected by CNV. Our analysis fixes the minimal length of proven CNV to 157 kb including DEFB108P but excluding DEFB109P. The distal border between CNV and non-CNV part of the DEF cluster is located in the 59 kb interval chr8:7,171,082-7,230,128.
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    • "The evolutionary history of these genes can be tracked throughout the genomes of distantly related species. However , certain human gene families do not seem to have clear orthologs in the mouse genome and some appear to be primate-specific (Johnson et al. 2001; Vandepoele et al. 2005; Hodzic et al. 2006; Bosch et al. 2007). The recent origin of these genes and the positive selection acting on some of them (Johnson et al. 2001) means that they might have been key players in the evolution of man. "
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    ABSTRACT: Most new genes arise through the duplication of existing genes. In most cases, the duplication is not limited to the coding sequence but encompasses the regulatory region as well. The NBPF gene family has expanded during recent primate evolution, and it has no known mouse ortholog. One of its members, NBPF1, was found to be disrupted by a constitutional translocation in a neuroblastoma patient. Here, we show that the ancestral NBPF gene copied the regulatory region from an unrelated gene, EVI5, after the split between simians and prosimians but before simian radiation. Phylogenetic analysis points to the possible involvement of positive selection acting on the NBPF1 promoter in the simian lineage. We previously showed decreased NBPF1 expression in certain neuroblastoma cell lines. Here, we show that this expression pattern is mimicked by the EVI5 gene, but partly by different mechanisms. Epigenetic regulation of the EVI5 promoter is common in neuroblastoma cell lines, but it is not for the NBPF promoters. Here, we describe the recent acquisition of the NBPF1 promoter from an unrelated gene, and remarkably, both the donor (EVI5) and acceptor (NBPF1) genes are disrupted by constitutional translocations in patients with neuroblastoma, suggesting a functional link between these genes and the disease.
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