The Birth of New Genes by RNA- and DNA-Mediated Duplication during Mammalian Evolution

Abstract

Gene duplication has long been recognized as a major force in genome evolution and has recently been recognized as an important source of individual variation. For many years, the origin of functional gene duplicates was assumed to be whole or partial genome duplication events, but recently retrotransposition has also been shown to contribute new functional protein coding genes and siRNA's. In this study, we utilize pseudogenes to recreate more complete gene family histories, and compare the rates of RNA and DNA-mediated duplication and new functional gene formation in five mammalian genomes. We find that RNA-mediated duplication occurs at a much higher and more variable rate than DNA-mediated duplication, and gives rise to many more duplicated sequences over time. We show that, while the chance of RNA-mediated duplicates becoming functional is much lower than that of their DNA-mediated counterparts, the higher rate of retrotransposition leads to nearly equal contributions of new genes by each mechanism. We also find that functional RNA-mediated duplicates are closer to neighboring genes than non-functional RNA-mediated copies, consistent with co-option of regulatory elements at the site of insertion. Overall, new genes derived from DNA and RNA-mediated duplication mechanisms are under similar levels of purifying selective pressure, but have broadly different functions. RNA-mediated duplication gives rise to a diversity of genes but is dominated by the highly expressed genes of RNA metabolic pathways. DNA-mediated duplication can copy regulatory material along with the protein coding region of the gene and often gives rise to classes of genes whose function are dependent on complex regulatory information. This mechanistic difference may in part explain why we find that mammalian protein families tend to evolve by either one mechanism or the other, but rarely by both. Supplementary Material has been provided (see online Supplementary Material at www.liebertonline.com ).

The Genomic Impact of Gene Retrocopies: What Have We Learned from Comparative Genomics, Population Genomics, and Transcriptomic Analyses?

“…In line with the neofunctionalization hypothesis, several papers have shown retrogenes that experienced an accelerated substitution rate in their coding sequence, compared with their cognate genes, in the early stage of their evolution (Betran and Long 2003; Jones and Begun 2005; Gayral et al 2007; Rosso, Marques, Reichert et al 2008; Jun et al 2009; Matsuno et al 2009; Quezada-Diaz et al 2010; Tracy et al 2010; Pegueroles et al 2013). These findings support Ohno’s view that after duplication, one of the two gene copies is free from selective constrains and therefore accumulates “forbidden” substitutions that can initiate the path to a novel function.…”

Tempo and Mode of Gene Duplication in Mammalian Ribosomal Protein Evolution

“…The precise combination of forces enabling the retention of duplicated genes in complex genomes leading to the formation of gene families has been a subject of much study [69], [70]. Several interesting studies have focused on the fate of ribosomal protein duplicates in non-mammalian lineages.…”

Interlocus gene conversion events introduce deleterious mutations into at least 1% of human genes associated with inherited disease

“…When acting as donor sequences in IGC events, pseudogenes generally introduce either missense or nonsense mutations, or indels that give rise to frameshifts. The vast majority of the pseudogene donor sequences were found to be nonprocessed copies, i.e., they were derived from a genomic DNAmediated duplication of the acceptor gene ( Jun et al 2009). However, we also found evidence supporting the occurrence of IGC from a processed pseudogene to the functional gene GJA1, encoding the gap junction protein connexin 43, which was associated with hypoplastic left heart syndrome (Dasgupta et al 2001).…”