Downloaded from genome. cshlporg on June 20, 2011-Published by Cold Spring Harbor Laboratory Press Review. Origins evolution and phenotypic impact of new genes Henrik Kaessmann Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland Ever since the pre-molecular era, the birth of new genes with novel functions has been considered to be a major con- tributor to adaptive evolutionary innovation. here, I review the origin and evolution of new genes and their functions in eukaryotes, an area of research that has made rapid progress in the past decade thanks to the genomics revolution. Indeed organisms. The array of mechanisms underlying the origin of new genes is compelling extending way beyond the tra ditionally well-studied source of gene duplication. Thus, it was shown that novel genes also regularly arose from mes- senger RNAs of ancestral genes, protein-coding genes metamorphosed into new rna genes, genomic parasites were co- opted as new genes, and that both protein and rna genes were composed from scratch (i.e from previously non- functional sequences). These mechanisms then also contributed to the formation of numerous novel chimeric gene structures. Detailed functional investigations uncovered different evolutionary pathways that led to the emergence of novel functions from these newly minted sequences and, with respect to animals attributed a potentially important role to one specific tissue-the testisin the process of gene birth Remarkably these studies also demonstrated that novel genes of the various types significantly impacted the evolution of cellular physiological, morphological, behavioral, and reproductive phenotypic traits. Consequently it is now firmly established that new genes have indeed been major con the origin of adap What is the nature of mutations underlying adaptive evolution- change, which further underscores the importance of novel gene ary innovations? In addition to subtle genetic modifications of for organismal evolution preexisting ancestral genes that can lead to differences in their In this review, I discuss in detail the different genomic sources (protein or RNA) sequences or activities, new genes with novel of new genes in eukaryotes(with a particular emphasis on animals) functions may have significantly contributed to the evolution of and assess their relative contributions and functional implications lineage- or species-specific phenotypic traits. Consequently, the in different species and evolutionary lineages. I also examine how process of the "birth"and evolution of novel genes has attracted new protein or RNA functions may evolve from newly minted gene much attention from biologists in the past. Indeed, quite re- structures and discuss the associated selective forces. I then discuss markably, considerations pertaining to the origin and functional a hypothesis that suggests a key role of one tissue-the testis-in ate of new genes trace back to a time when the molecular nature of the establishment of new functional genes. Finally, I highlight enes had not yet been established. Based on cytological obser- recent new developments in the field and identify potential future vations of chromosomal duplications, Haldane(1933)and Muller research directions. Notably, I focus on recent developments in (1935)already hypothesized in the 1930s that new gene functions this review, while referring to previous reviews and other litera may emerge from refashioned copies of old genes, highlighting ture for details pertaining to long-established concepts and earlier for the first time the potential importance of gene duplication for findings the process of new gene origination. The early notions that gene duplication provides a significant reservoir for the emep globally of new genes of genes and hence phenotypic adaptation have now be Gene duplication-raw material for the emergence confirmed (but also refined) based on numerous large- and small scale molecular studies that were facilitated by the genomics rev. Gene duplication is a very common phenomenon in all eukaryotic olution. New duplicate genes have been shown to be abundant organisms(but also in prokaryotes; for review, see Romero and in all eukaryotic genomes sequenced to date and to have evolved Palacios 1997) that may occur in several different ways ( lynch pivotal functional roles(Lynch 2007) 2007). Traditionally, DNA-mediated duplication mechanisms have However, studies from the genomics era have also accelerated been considered and widely studied in this context, although pe. the discovery of fascinating novel mechanisms underlying the culiar intronless duplicate gene copies may also arise from RNA emergence of new genes. These include the origin of new protein- sources(see further below). DNA duplication mechanisms include coding and RNA genes"from scratch"(that is, from previously small-scale events, such as the duplication of chromosomal seg. nonfunctional genomic sequences), various types of gene fusions, ments containing whole genes or gene fragments(termed seg and the formation of new genes from RNA intermediates. It is now mental duplication), which are essentially outcomes of misguided well established that all of these mechanisms have significantly recombination processes during meiosis(Fig. 1A).However, they ontributed to functional genome evolution and phenotypic also include duplication of whole genomes through various poly ploidization mechanisms(Lynch 2007; Conant and Wolfe 2008; I Henrik Kaessmann unilch Van de peer et al. 2009). Thus, duplicate gene copies can arise in 加m blished online before print. Article and publication date are at many different ways. But what is their functional fate and evolu- wwwgenome. org/cgi/doi/10. 1101/gr. 101386 tionary relevance? :0 1313-1326 e 2010 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/10: Genome Research 1313Review Origins, evolution, and phenotypic impact of new genes Henrik Kaessmann1 Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland Ever since the pre-molecular era, the birth of new genes with novel functions has been considered to be a major con￾tributor to adaptive evolutionary innovation. Here, I review the origin and evolution of new genes and their functions in eukaryotes, an area of research that has made rapid progress in the past decade thanks to the genomics revolution. Indeed, recent work has provided initial whole-genome views of the different types of new genes for a large number of different organisms. The array of mechanisms underlying the origin of new genes is compelling, extending way beyond the tra￾ditionally well-studied source of gene duplication. Thus, it was shown that novel genes also regularly arose from mes￾senger RNAs of ancestral genes, protein-coding genes metamorphosed into new RNA genes, genomic parasites were co￾opted as new genes, and that both protein and RNA genes were composed from scratch (i.e., from previously non￾functional sequences). These mechanisms then also contributed to the formation of numerous novel chimeric gene structures. Detailed functional investigations uncovered different evolutionary pathways that led to the emergence of novel functions from these newly minted sequences and, with respect to animals, attributed a potentially important role to one specific tissue—the testis—in the process of gene birth. Remarkably, these studies also demonstrated that novel genes of the various types significantly impacted the evolution of cellular, physiological, morphological, behavioral, and reproductive phenotypic traits. Consequently, it is now firmly established that new genes have indeed been major con￾tributors to the origin of adaptive evolutionary novelties. What is the nature of mutations underlying adaptive evolution￾ary innovations? In addition to subtle genetic modifications of preexisting ancestral genes that can lead to differences in their (protein or RNA) sequences or activities, new genes with novel functions may have significantly contributed to the evolution of lineage- or species-specific phenotypic traits. Consequently, the process of the ‘‘birth’’ and evolution of novel genes has attracted much attention from biologists in the past. Indeed, quite re￾markably, considerations pertaining to the origin and functional fate of new genes trace back to a time when the molecular nature of genes had not yet been established. Based on cytological obser￾vations of chromosomal duplications, Haldane (1933) and Muller (1935) already hypothesized in the 1930s that new gene functions may emerge from refashioned copies of old genes, highlighting for the first time the potential importance of gene duplication for the process of new gene origination. The early notions that gene duplication provides a significant reservoir for the emergence of genes and hence phenotypic adaptation have now been globally confirmed (but also refined) based on numerous large- and small￾scale molecular studies that were facilitated by the genomics rev￾olution. New duplicate genes have been shown to be abundant in all eukaryotic genomes sequenced to date and to have evolved pivotal functional roles (Lynch 2007). However, studies from the genomics era have also accelerated the discovery of fascinating novel mechanisms underlying the emergence of new genes. These include the origin of new protein￾coding and RNA genes ‘‘from scratch’’ (that is, from previously nonfunctional genomic sequences), various types of gene fusions, and the formation of new genes from RNA intermediates. It is now well established that all of these mechanisms have significantly contributed to functional genome evolution and phenotypic change, which further underscores the importance of novel genes for organismal evolution. In this review, I discuss in detail the different genomic sources of new genes in eukaryotes (with a particular emphasis on animals) and assess their relative contributions and functional implications in different species and evolutionary lineages. I also examine how new protein or RNA functions may evolve from newly minted gene structures and discuss the associated selective forces. I then discuss a hypothesis that suggests a key role of one tissue—the testis—in the establishment of new functional genes. Finally, I highlight recent new developments in the field and identify potential future research directions. Notably, I focus on recent developments in this review, while referring to previous reviews and other litera￾ture for details pertaining to long-established concepts and earlier findings. Gene duplication—raw material for the emergence of new genes Gene duplication is a very common phenomenon in all eukaryotic organisms (but also in prokaryotes; for review, see Romero and Palacios 1997) that may occur in several different ways (Lynch 2007). Traditionally, DNA-mediated duplication mechanisms have been considered and widely studied in this context, although pe￾culiar intronless duplicate gene copies may also arise from RNA sources (see further below). DNA duplication mechanisms include small-scale events, such as the duplication of chromosomal seg￾ments containing whole genes or gene fragments (termed seg￾mental duplication), which are essentially outcomes of misguided recombination processes during meiosis (Fig. 1A). However, they also include duplication of whole genomes through various poly￾ploidization mechanisms (Lynch 2007; Conant and Wolfe 2008; Van de Peer et al. 2009). Thus, duplicate gene copies can arise in many different ways. But what is their functional fate and evolu￾tionary relevance? 1 E-mail Henrik.Kaessmann@unil.ch. Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.101386.109. 20:1313–1326 2010 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/10; www.genome.org Genome Research 1313 www.genome.org Downloaded from genome.cshlp.org on June 20, 2011 - Published by Cold Spring Harbor Laboratory Press