Downloaded from genome. cshlporg on June 20, 2011-Published by Cold Spring Harbor Laboratory Press Evolution of new genes A encoded proteins were co-opted to me- diate crucial functions in placentation That is, they are essential for the devel- evil an exterio structure of the placenta that is essential for proper nutrient and waste exchange between mother and fetus. Thus, the eu- therian placenta, a recent evolutionary innovation, appears to have provided a particularly fruitful ground for the emer- gence of new domesticated genes with beneficial functions, a view that is further supported by the observation that tv Formation of functional RNA gene Rtil also known as Peg1l) have similarly adopted key functional roles in the murine placenta(Onoet al. 2006; Sekita et al. 2008) However. other functional roles have been assigned to"tamed"genomic para- sites as well. For instance. a recent study traced the birth of a new transcription factor gene(Zbedo) back to the domestica- of protein function and pseudogenization tion of a DNA transposon in the common ancestor of eutherians (Markljung et al. 2009). ZBED6 has evolved key regulatory roles in muscle growth, but, interestingly may affect the expression of thousands of other genes that control fundamental nd therefore could sequences) underlie the evolution of a completely new Noncoding RNAs from transposable elements In addition to various other protein-coding Figure 4. Evolutionary origins of long noncoding RNA genes. (A) De novo emergence. In this sce. genes that arose on the basis of transpos- d(thin red box) through the able element sequences in diverse taxa(i.e, acquisition/activation of a proto-promoter sequence (right-angled arrows). The transcriptional activa. vertebrates, fruit flies, and plants; Volff thone ding RNA we nes heate red bo t xons, thin tack li aes splicing red nighit-a mled aows were shown to represent "reincamated rise, a process that may draw from regulatory elements and other sequences(splicing signals, exon these genes evolved independently from Protein-coding exons, (red boxes) RNA exons,(transparent boxes) pseudogenized sne.( Blue boxes) retrotransposons in rodents and anthro- sequences, etc. )from the ancestral protein-coding ons,(thin black lines)splicing, (dotted lines) lost ancestral splicing capacity, (red right-angled arrows) TSSs poid primates(Brosius 1999), they adapted to similar roles in translational regulation the brain(Cao et al. 2006). while ca of lncRNAs that were derived from transposon ancestors are so far scarce, new small RNA genes seem to rather frequently have emerged It has been known for quite some time that transposable elements from transposable elements. For example, retrotransposon conver- have frequently been incorporated into genes as new exons, a pro- sions have given rise to dozens of known lineage-specific miRNAs cess frequently associated with alternative splicing(Sorek 2007). in mammals(Smalheiser and Torvik 2005; Piriyapongsa et al. 2007) However, the functional significance of these "exonization"even Finally, the germline-expressed piRNAs and endo-siRNAs should also has remained elusive. More strikingly, a number of new genes that be mentioned in thi were, by and large, entirely derived from genome "parasites"and from the various lineage-specific transposable elements that they evolved beneficial functions for the host organism have been then control (Malone and Hannon 2009) dentified in recent years(Volff 2006; Feschotte and Pritham 2007) Examples for such"domesticated"parasites are the syncytin genes, which stem from envelope genes of endogenous retroviruses and Horizontal gene transfer originated independently in primates, rodents, and lagomorphs Horizontal gene transfer(HGT; also known as lateral gene transfer) (Fig. 5: Miet al. 2000; Dupressoiret al. 2009; Heidmann et al. 2009). is the process by which an organism incorporates genetic material Remarkably, in all of these mammalian lineages, the syncytin- from another organism without being a direct descendant of that ome research 1321Protein-coding genes from genome parasites It has been known for quite some time that transposable elements have frequently been incorporated into genes as new exons, a pro￾cess frequently associated with alternative splicing (Sorek 2007). However, the functional significance of these ‘‘exonization’’ events has remained elusive. More strikingly, a number of new genes that were, by and large, entirely derived from genome ‘‘parasites’’ and evolved beneficial functions for the host organism have been identified in recent years (Volff 2006; Feschotte and Pritham 2007). Examples for such ‘‘domesticated’’ parasites are the syncytin genes, which stem from envelope genes of endogenous retroviruses and originated independently in primates, rodents, and lagomorphs (Fig. 5; Mi et al. 2000; Dupressoir et al. 2009; Heidmann et al. 2009). Remarkably, in all of these mammalian lineages, the syncytin￾encoded proteins were co-opted to me￾diate crucial functions in placentation. That is, they are essential for the devel￾opment of the ‘‘syncytium,’’ an exterior structure of the placenta that is essential for proper nutrient and waste exchange between mother and fetus. Thus, the eu￾therian placenta, a recent evolutionary innovation, appears to have provided a particularly fruitful ground for the emer￾gence of new domesticated genes with beneficial functions, a view that is further supported by the observation that two retrotransposon-derived genes (Peg10 and Rt11 [also known as Peg11]) have similarly adopted key functional roles in the murine placenta (Ono et al. 2006; Sekita et al. 2008). However, other functional roles have been assigned to ‘‘tamed’’ genomic para￾sites as well. For instance, a recent study traced the birth of a new transcription factor gene (Zbed6) back to the domestica￾tion of a DNA transposon in the common ancestor of eutherians (Markljung et al. 2009). ZBED6 has evolved key regulatory roles in muscle growth, but, interestingly, may affect the expression of thousands of other genes that control fundamental biological processes and therefore could underlie the evolution of a completely new regulatory network in placental mammals. Noncoding RNAs from transposable elements In addition to various other protein-coding genes that arose on the basis of transpos￾able element sequences in diverse taxa (i.e., vertebrates, fruit flies, and plants; Volff 2006), several long and small RNA genes were shown to represent ‘‘reincarnated’’ retrotransposons. This process is exempli￾fied by the origin of the brain cytoplasmic lncRNA genes (BC1 and BC200). Although these genes evolved independently from retrotransposons in rodents and anthro￾poid primates (Brosius 1999), they adapted to similar roles in translational regulation in the brain (Cao et al. 2006). While cases of lncRNAs that were derived from transposon ancestors are so far scarce, new small RNA genes seem to rather frequently have emerged from transposable elements. For example, retrotransposon conver￾sions have given rise to dozens of known lineage-specific miRNAs in mammals (Smalheiser and Torvik 2005; Piriyapongsa et al. 2007). Finally, the germline-expressed piRNAs and endo-siRNAs should also be mentioned in this context, because they are frequently derived from the various lineage-specific transposable elements that they then control (Malone and Hannon 2009). Horizontal gene transfer Horizontal gene transfer (HGT; also known as lateral gene transfer) is the process by which an organism incorporates genetic material from another organism without being a direct descendant of that Figure 4. Evolutionary origins of long noncoding RNA genes. (A) De novo emergence. In this sce￾nario, previously nonfunctional genomic sequence becomes transcribed (thin red box) through the acquisition/activation of a proto-promoter sequence (right-angled arrows). The transcriptional activa￾tion may be followed or preceded by the evolution of (proto-) splice sites (light blue stars). Together, these events allow for the formation of potentially functional and selectively beneficial multi-exonic noncoding RNA genes. (Large red boxes) Exons, (thin black lines) splicing, (red right-angled arrows) TSSs. (B) Origin of noncoding RNA gene from ancestral protein-coding gene. In this process, the original (functionally redundant) protein-coding gene loses its function and becomes a pseudogene. After or during loss of protein function and coding exon decay, a new functional noncoding RNA gene may arise, a process that may draw from regulatory elements and other sequences (splicing signals, exon sequences, polyadenylation sequences, etc.) from the ancestral protein-coding gene. (Blue boxes) Protein-coding exons, (red boxes) RNA exons, (transparent boxes) pseudogenized exons, (thin black lines) splicing, (dotted lines) lost ancestral splicing capacity, (red right-angled arrows) TSSs. Evolution of new genes Genome Research 1321 www.genome.org Downloaded from genome.cshlp.org on June 20, 2011 - Published by Cold Spring Harbor Laboratory Press