Downloaded from genome. cshlporg on June 20, 2011-Published by Cold Spring Harbor Laboratory Press Kaessmann A time that the most probable fate of a du- plicate gene copy is pseudogenization (Ohno 1972)and that hence the majority of duplicate gene copies are eventually lost from the genome. While these fundamental hypot ses have been confirmed by a large bod of data, they have since also been signif icantly extended and refined In particu- Unequal crossing-ov 人上一 lar, in addition to the process of neo- functionalization (i.e., the emergence of new functions from one copy-Ohno's basic concept), it was proposed that the 上个:已个m斯mm be shaped by natural selection or in volve purely neutral processes(Force et al. 1999: Conant and wolfe 2008: Innan and Kondrashov 2010 Global genomic screens combined with detailed experimental scrutiny have uncovered numerous intriguing examples Transcription AAA ganisms, solidly supporting their validity Detailed analyses of young duplicate gen Reverse transcription and integration have been particularly informative, be. cause many of the details associated with the emergence of new genes from gene duplicates become obscured over longer periods of time(Long et al. 2003). A pa Figure 1. Origin of new gene copies through gene duplication. (A) DNA-based duplication. a ticularly illustrative case of neofunction- via unequal alization, arguably the most intriguing ossing-over that is mediated by transposable elements(light green). There are different fates of fate of a duplicate gene, occurred in the ication). New retroposed gene copies may arise after duplication in an African leaf-eating monkey, the protein encoded by one of evolution of promoters in their 5 flanking regions that may drive their transcription. (Pink right. the copies of the ancestral RNASEI gene ngled arrow TSS, (transparent pink box) additionally transcribed flanking sequence at the insertion rapidly adapted at specific sites to derive nutrients from bacteria in the foregut under the influence of strong positive selection( Zhang et al. 2002). Remarkably, Gene duplication and new gene functions both the duplication and subsequent adaptation of this gene were later shown to have occurred independently in a very similar At least since a famous monograph, authored by Susumu Ohno, manner in an Asian leaf-eating monkey(Zhang 2006). Thus, these vas published over 40 yr ago(Ohno 1970), the word has spread RNASEl duplications represent striking cases of convergent hat gene duplication may underlie the origin of many or even lecular evolution. They were likely facilitated by the frequent oc. most novel genes and hence represents an important process for currence of segmental duplication, which allows similar duplica- functional innovation during evolution. Essentially and consis- tion events that are highly beneficial to be repeatedly fixed during tent with earlier ideas(Haldane 1933; Muller 1935), Ohno em- evolution. More generally, the convergent RNASEI duplications phasized that the presence of a second copy of a gene would open are in line with several other recent reports that include other cases up unique new opportunities in evolution by allowing one of the of new gene formation(see below)and therefore lend further two duplicate gene copies to evolve new functional properties, support to the more general idea that adaptive genome evolution whereas the other copy is preserved to take care of the ancestral is, to some extent, predictable(Stern and Orgogozo 2009). Nu (usually important) function(the concept of neofunctionalization). merous other classical or recent examples from diverse organisms Ohno also reviewed that duplicate genes can be preserved by could be discussed here that illustrate the immense potential that natural selection for gene dosage, thus allowing an increased DNA-based gene duplication has held for phenotypic evolution production of the ancestral gene product(Ohno 1970). Finally, it in different organisms(for reviews, see Li 1997; Long et al. 2003; should be emphasized that it has been widely agreed for a long Zhang 2003; Lynch 2007; Conant and wolfe 2008) 1314 GenomeGene duplication and new gene functions At least since a famous monograph, authored by Susumu Ohno, was published over 40 yr ago (Ohno 1970), the word has spread that gene duplication may underlie the origin of many or even most novel genes and hence represents an important process for functional innovation during evolution. Essentially and consis￾tent with earlier ideas (Haldane 1933; Muller 1935), Ohno em￾phasized that the presence of a second copy of a gene would open up unique new opportunities in evolution by allowing one of the two duplicate gene copies to evolve new functional properties, whereas the other copy is preserved to take care of the ancestral (usually important) function (the concept of neofunctionalization). Ohno also reviewed that duplicate genes can be preserved by natural selection for gene dosage, thus allowing an increased production of the ancestral gene product (Ohno 1970). Finally, it should be emphasized that it has been widely agreed for a long time that the most probable fate of a du￾plicate gene copy is pseudogenization (Ohno 1972) and that hence the majority of duplicate gene copies are eventually lost from the genome. While these fundamental hypothe￾ses have been confirmed by a large body of data, they have since also been signif￾icantly extended and refined. In particu￾lar, in addition to the process of neo￾functionalization (i.e., the emergence of new functions from one copy—Ohno’s basic concept), it was proposed that the potentially multiple functions of an an￾cestral gene may be partitioned between the two daughter copies. This process was dubbed ‘‘subfunctionalization’’ and may be shaped by natural selection or in￾volve purely neutral processes (Force et al. 1999; Conant and Wolfe 2008; Innan and Kondrashov 2010). Global genomic screens combined with detailed experimental scrutiny have uncovered numerous intriguing examples for each of these models in many or￾ganisms, solidly supporting their validity. Detailed analyses of young duplicate genes have been particularly informative, be￾cause many of the details associated with the emergence of new genes from gene duplicates become obscured over longer periods of time (Long et al. 2003). A par￾ticularly illustrative case of neofunction￾alization, arguably the most intriguing fate of a duplicate gene, occurred in the course of the recent duplication of a pan￾creatic ribonuclease gene in leaf-eating monkeys. Zhang et al. demonstrated that after duplication in an African leaf-eating monkey, the protein encoded by one of the copies of the ancestral RNASE1 gene rapidly adapted at specific sites to derive nutrients from bacteria in the foregut under the influence of strong positive selection (Zhang et al. 2002). Remarkably, both the duplication and subsequent adaptation of this gene were later shown to have occurred independently in a very similar manner in an Asian leaf-eating monkey (Zhang 2006). Thus, these RNASE1 duplications represent striking cases of convergent mo￾lecular evolution. They were likely facilitated by the frequent oc￾currence of segmental duplication, which allows similar duplica￾tion events that are highly beneficial to be repeatedly fixed during evolution. More generally, the convergent RNASE1 duplications are in line with several other recent reports that include other cases of new gene formation (see below) and therefore lend further support to the more general idea that adaptive genome evolution is, to some extent, predictable (Stern and Orgogozo 2009). Nu￾merous other classical or recent examples from diverse organisms could be discussed here that illustrate the immense potential that DNA-based gene duplication has held for phenotypic evolution in different organisms (for reviews, see Li 1997; Long et al. 2003; Zhang 2003; Lynch 2007; Conant and Wolfe 2008). Figure 1. Origin of new gene copies through gene duplication. (A) DNA-based duplication. A common type of segmental duplication—tandem duplication—is shown. It may occur via unequal crossing-over that is mediated by transposable elements (light green). There are different fates of the resulting duplicate genes. For example, one of the duplicates may acquire new functions by evolving new expression patterns and/or novel biochemical protein or RNA functions (see main text for details). (Gold and blue boxes) Exons, (black connecting lines) exon splicing, (red right￾angled arrows) transcriptional start sites (TSSs), (gray tubes) nonexonic chromatin. (B) RNA-based duplication (termed retroposition or retroduplication). New retroposed gene copies may arise through the reverse transcription of messenger RNAs (mRNAs) from parental source genes. Func￾tional retrogenes with new functional properties may evolve from these copies after acquisition or evolution of promoters in their 59 flanking regions that may drive their transcription. (Pink right￾angled arrow) TSS, (transparent pink box) additionally transcribed flanking sequence at the insertion site. 1314 Genome Research www.genome.org Kaessmann Downloaded from genome.cshlp.org on June 20, 2011 - Published by Cold Spring Harbor Laboratory Press