Origin of Primate Orphan Genes: A Comparative Genomics Approach

Abstract

Genomes contain a large number of genes that do not have recognizable homologues in other species and that are likely to be involved in important species-specific adaptive processes. The origin of many such "orphan" genes remains unknown. Here we present the first systematic study of the characteristics and mechanisms of formation of primate-specific orphan genes. We determine that codon usage values for most orphan genes fall within the bulk of the codon usage distribution of bona fide human proteins, supporting their current protein-coding annotation. We also show that primate orphan genes display distinctive features in relation to genes of wider phylogenetic distribution: higher tissue specificity, more rapid evolution, and shorter peptide size. We estimate that around 24% are highly divergent members of mammalian protein families. Interestingly, around 53% of the orphan genes contain sequences derived from transposable elements (TEs) and are mostly located in primate-specific genomic regions. This indicates frequent recruitment of TEs as part of novel genes. Finally, we also obtain evidence that a small fraction of primate orphan genes, around 5.5%, might have originated de novo from mammalian noncoding genomic regions.

Recent de novo origin of human protein-coding genes

“…Prior to this study, there were few reports of novel gene origination by this mechanism and none identified human-specific genes (Levine et al 2006;Begun et al 2007;Cai et al 2008;Zhou et al 2008;Toll-Riera et al 2009). The novel proteins identified in this study are all short, encoded by an uninterrupted ORF, are supported by expression data, and the corresponding regions of chromosome where the ortholog is expected to be found in chimp and macaque harbor disabling mutations, which mean that the protein cannot be produced.…”

“…New genes frequently arise through duplication of existing genes, or through fusion, fission, or exon shuffling between genes (Long et al 2003). Origination of genes from noncoding DNA is extremely rare: A few eukaryotic examples are known in yeast and Drosophila (Levine et al 2006;Begun et al 2007;Cai et al 2008;Zhou et al 2008) and a very recent paper reported initial evidence for this process in a primate ancestor (Toll-Riera et al 2009). No cases have been previously reported in human.…”

Partial Gene Duplication and the Formation of Novel Genes

“…These young genes were found to evolve very rapidly, showing a median of 47.3% divergence, at the amino-acid level, from their parents. In an analysis of the mechanisms of formation of primate-specific genes, we observed that about 24% of the newly formed genes had originated through gene duplication, frequently involving partial gene duplication and the recruitment of additional sequences (Toll-Riera et al, 2009a). One example is human XAGE-1, a cancer/testis-associated gene that has partial homology to human XAGE-2, a gene that is well conserved in other mammals.…”

Genome-wide identification of lineage-specific genes within Caenorhabditis elegans

“…In contrast, lineagespecific genes (LSGs), which are also referred to as taxonomically restricted genes that share no sequence similarity with genes of other lineages in one taxonomic group [2][3][4][5][6][7][8], are often ignored in genomics. However, study of these genes is helpful to aid in the comprehensive understanding of a species.…”

“…However, study of these genes is helpful to aid in the comprehensive understanding of a species. With the increasing development of sequencing technologies, we have gained access to a number of genomes and transcriptomes from a wide range of species, which has aided the extensive study of the LSGs within mammals [8][9][10], insects [2,11,12], fish [13], plants [5,[14][15][16], and microbial species [17][18][19][20]. However, the LSGs in C. elegans have not yet been researched through genomewide methods.…”