Downloaded from genome. cshlporg on June 20, 2011-Published by Cold Spring Harbor Laboratory Press Evolution of new genes Duplication of noncoding RNAs For example, analyses of fully sequenced genomes have Suffice it to add in this review that studies pertaining to the origin revealed high rates of origin but also loss of duplicate genes(Lynch of novel genes from duplicated DNA segments have begun to be d Conery 2003; Demuth and Hahn 2009). New duplicates are extended beyond the traditionally studied protein-coding gene estimated to be "born"at the rate of -0 001 thanks to the rapid recent advances in the genomics field. For million years in eukaryotes (Lynch and Conery 2003; Lynch 2007 example, it has become clear that microRNAs(miRNAs), small rna while the death rate of duplicates is at least an order of magnitude molecules that have emerged as major post-transcriptional regu. higher, consistent with the early notion(see above) that the fate lators( Carthew and Sontheimer 2009), have expanded and func- f most duplicates is pseudogenization(Ohno 1972). Notably, not all functional categories of genes are equally prone to expand by et al. 2006). Interestingly, several individual studies indicate that duplication. In particular, a relatively small number of gene fami- the X chromosome may provide a particularly fruitful ground for lies(1.6%3%)with functions in, for example, immunity, host the origination of new lineage-specific miRNAs(Zhanget al. 2007: defense, chemosensation, and reproduction, show rapid, selec Devor and Samollow 2008: Murchison et al. 2008: Guoet al 2009), tively driven copy number changes in various eukaryotic lineages, a pattern that may be explained by the specific sex-related forces ing to that have shaped the x, given that new X-born miRNAs appear et al. 2003; Demuth and Hahn 2009) to be However, in addition to these commonalities detailed whole. mental gene duplication also seems to play a major role for the genome investigations also suggest intriguing fundamental dif- expansion of another class of small RNAS, Piwi-interacting RNAs ferences with respect to the generation and functional fate of du- (piRNAs, Malone and Hannon 2009), which are expressed in the plicates in different evolutionary lineages. For example, careful germline and are thought to be mainly involved in transposon analyses in primates revealed a burst of segmental gene duplication control. A recent study revealed that pirNA clusters rapidly in hominoids(humans and apes), especially in humans and the genomes, a process driven by intense positive selection(Assis and of these duplicates are dispersed and mediate major gend rearrangements associated with disease. The accelerated fixation Kondrashov 2009). Segmental duplication therefore provides an rate of segmental duplicons in hominoids could, in principle, be efficient vehicle for the expansion of piRNA repertoires and hen allows organisms to swiftly evolve protection barriers against the lained by the selective benefit of newly formed genes embed- lineage-specific expansion of transposable elements. There is so far ded within these s, which outweigh deleterious effects in many cases(Marques-Bonet et al. 2009b). New gene formation in little evidence for duplication of sequences transcribed into long hominoids indeed seems to have profited from the substantial raw noncoding RNAs(lnCRNAs), an abundant class of nontranslated RNAs(>200 nucleotides [nt] in length), whose functional impact material provide led by massive segmental duplication(Marques- is only beginning to be understood (Mercer et al. 2009; Ponting Bonet et al. 2009b; see below). However, the overall accelerated et al. 2009). The paucity of known duplicated IncRNA genes is fixation rate of segmental duplicons in humans and apes is prob- perhaps mainly due to their rapid sequence divergence, which ably best explained by the reduction of the effective population which will benefit from the rapidly accumulating genomic and drift and, at the same time, rendered purifying selection less effi- transcriptomic data, will clarify the role of gene duplication in the cient, thus probably allowing disproportionately high numbers of evolution of new IncRNA genes with altered or novel functions. lightly deleterious segmental duplications to be fixed in homi- noids compared with other species with larger long-term effective Global patterns population sizes (and hence more efficient selection). This hy pothesis is consistent with other types of molecular evolutionary n spite of the numerous well-founded examples of functionally data(Keightley et al. 2005; Gherman et al. 2007) important newly minted genes that arose from duplicate gene In addition to lineage-specific selection intensities, differ copies, a more global picture of the functional relevance and ences pertaining to the mutational basis of gene duplication can adaptive value of the large number of duplicate gene copies scat- lead to different characteristics of segmental duplications between tered in genomes is only beginning to emerge. Only for some species. a good example is the finding that, in contrast to humans, whole-genome duplication (WGD) events in model organisms recently duplicated chromosomal regions in the mouse are de- (in particular yeast), global assessments of the relevance of dupli- pleted in genes and transcriptsShe et al. 2008). Detailed analyses cate genes for the emergence of new gene functions have been suggest that species-specific distributions of retrotransposons tempted( Conant and wolfe 2008). However, WGD represents a which represent major promoters of segmental duplication events special case of gene duplication, which involves specific selective ( Marques-Bonet et al. 2009a), account for much of this discrepancy pressures related to dosage balance of gene products that seem to ignificantly influence the fate of resulting gene duplicates And RNA-based duplication and the emergence ven in the case of WGD, it remains largely unclear whether gene duplications often conferred novel functions or not( Conant ar of"stripped-down"new genes Wolfe 2008) As outlined above, the traditionally studied DNA-mediated gene Thus, a more global understanding of the implications of duplication mechanisms have significantly contributed to fund gene duplication for the emergence of new gene functions and its tional genome evolution and have provided many fundamental importance relative to other mutational mechanisms that affect insights regarding new gene origination. However, new gene preexisting genes will have to await future efforts. However, a copies can also arise through an alternative, less well known closer examination of the reported general distributions and char- duplication mechanism termed retroposition or retroduplication acteristics of gene duplicates in different genomes is nevertheless(Brosius 1991; Long et al. 2003; Kaessmann et al. 2009). In this instructive mechanism, a mature messenger RNA (mRNA) that is transcribed Genome Research 1315Duplication of noncoding RNAs Suffice it to add in this review that studies pertaining to the origin of novel genes from duplicated DNA segments have begun to be extended beyond the traditionally studied protein-coding genes, thanks to the rapid recent advances in the genomics field. For example, it has become clear that microRNAs (miRNAs), small RNA molecules that have emerged as major post-transcriptional regu￾lators (Carthew and Sontheimer 2009), have expanded and func￾tionally diversified during evolution by gene duplication (Hertel et al. 2006). Interestingly, several individual studies indicate that the X chromosome may provide a particularly fruitful ground for the origination of new lineage-specific miRNAs (Zhang et al. 2007; Devor and Samollow 2008; Murchison et al. 2008; Guo et al. 2009), a pattern that may be explained by the specific sex-related forces that have shaped the X, given that new X-born miRNAs appear to be predominantly expressed in male-reproductive tissues. Seg￾mental gene duplication also seems to play a major role for the expansion of another class of small RNAs, Piwi-interacting RNAs (piRNAs, Malone and Hannon 2009), which are expressed in the germline and are thought to be mainly involved in transposon control. A recent study revealed that piRNA clusters rapidly ex￾panded through segmental duplication in primate and rodent genomes, a process driven by intense positive selection (Assis and Kondrashov 2009). Segmental duplication therefore provides an efficient vehicle for the expansion of piRNA repertoires and hence allows organisms to swiftly evolve protection barriers against the lineage-specific expansion of transposable elements. There is so far little evidence for duplication of sequences transcribed into long noncoding RNAs (lncRNAs), an abundant class of nontranslated RNAs (>200 nucleotides [nt] in length), whose functional impact is only beginning to be understood (Mercer et al. 2009; Ponting et al. 2009). The paucity of known duplicated lncRNA genes is perhaps mainly due to their rapid sequence divergence, which may render the detection of such events difficult. Future work, which will benefit from the rapidly accumulating genomic and transcriptomic data, will clarify the role of gene duplication in the evolution of new lncRNA genes with altered or novel functions. Global patterns In spite of the numerous well-founded examples of functionally important newly minted genes that arose from duplicate gene copies, a more global picture of the functional relevance and adaptive value of the large number of duplicate gene copies scat￾tered in genomes is only beginning to emerge. Only for some whole-genome duplication (WGD) events in model organisms (in particular yeast), global assessments of the relevance of dupli￾cate genes for the emergence of new gene functions have been attempted (Conant and Wolfe 2008). However, WGD represents a special case of gene duplication, which involves specific selective pressures related to dosage balance of gene products that seem to significantly influence the fate of resulting gene duplicates. And even in the case of WGD, it remains largely unclear whether gene duplications often conferred novel functions or not (Conant and Wolfe 2008). Thus, a more global understanding of the implications of gene duplication for the emergence of new gene functions and its importance relative to other mutational mechanisms that affect preexisting genes will have to await future efforts. However, a closer examination of the reported general distributions and char￾acteristics of gene duplicates in different genomes is nevertheless instructive. For example, analyses of fully sequenced genomes have revealed high rates of origin but also loss of duplicate genes (Lynch and Conery 2003; Demuth and Hahn 2009). New duplicates are estimated to be ‘‘born’’ at the rate of ;0.001–0.01 per gene per million years in eukaryotes (Lynch and Conery 2003; Lynch 2007), while the death rate of duplicates is at least an order of magnitude higher, consistent with the early notion (see above) that the fate of most duplicates is pseudogenization (Ohno 1972). Notably, not all functional categories of genes are equally prone to expand by duplication. In particular, a relatively small number of gene fami￾lies (1.6%–3%) with functions in, for example, immunity, host defense, chemosensation, and reproduction, show rapid, selec￾tively driven copy number changes in various eukaryotic lineages, thus significantly contributing to their adaptive evolution (Emes et al. 2003; Demuth and Hahn 2009). However, in addition to these commonalities, detailed whole￾genome investigations also suggest intriguing fundamental dif￾ferences with respect to the generation and functional fate of du￾plicates in different evolutionary lineages. For example, careful analyses in primates revealed a burst of segmental gene duplication in hominoids (humans and apes), especially in humans and the African apes (Marques-Bonet and Eichler 2009). Notably, many of these duplicates are dispersed and mediate major genomic rearrangements associated with disease. The accelerated fixation rate of segmental duplicons in hominoids could, in principle, be explained by the selective benefit of newly formed genes embed￾ded within these regions, which outweigh deleterious effects in many cases (Marques-Bonet et al. 2009b). New gene formation in hominoids indeed seems to have profited from the substantial raw material provided by massive segmental duplication (Marques￾Bonet et al. 2009b; see below). However, the overall accelerated fixation rate of segmental duplicons in humans and apes is prob￾ably best explained by the reduction of the effective population size in the hominoid lineage. This reduction increased genetic drift and, at the same time, rendered purifying selection less effi￾cient, thus probably allowing disproportionately high numbers of slightly deleterious segmental duplications to be fixed in homi￾noids compared with other species with larger long-term effective population sizes (and hence more efficient selection). This hy￾pothesis is consistent with other types of molecular evolutionary data (Keightley et al. 2005; Gherman et al. 2007). In addition to lineage-specific selection intensities, differ￾ences pertaining to the mutational basis of gene duplication can lead to different characteristics of segmental duplications between species. A good example is the finding that, in contrast to humans, recently duplicated chromosomal regions in the mouse are de￾pleted in genes and transcripts (She et al. 2008). Detailed analyses suggest that species-specific distributions of retrotransposons, which represent major promoters of segmental duplication events (Marques-Bonet et al. 2009a), account for much of this discrepancy. RNA-based duplication and the emergence of ‘‘stripped-down’’ new genes As outlined above, the traditionally studied DNA-mediated gene duplication mechanisms have significantly contributed to func￾tional genome evolution and have provided many fundamental insights regarding new gene origination. However, new gene copies can also arise through an alternative, less well known duplication mechanism termed retroposition or retroduplication (Brosius 1991; Long et al. 2003; Kaessmann et al. 2009). In this mechanism, a mature messenger RNA (mRNA) that is transcribed Evolution of new genes Genome Research 1315 www.genome.org Downloaded from genome.cshlp.org on June 20, 2011 - Published by Cold Spring Harbor Laboratory Press