Frequent ploidy changes in Salicaceae indicates widespread sharing of the salicoid whole genome duplication by the relatives of Populus L. and Salix L.

BACKGROUNDS: Populus and Salix belong to Salicaceae and are used as models to investigate woody plant physiology. The variation of karyotype and nuclear DNA content can partly reflect the evolutionary history of the whole genome, and can provide critical information for understanding, predicting, and potentially ameliorating the woody plant traits. Therefore, it is essential to study the chromosome number (CN) and genome size in detail to provide information for revealing the evolutionary process of Salicaceae. RESULTS: In this study, we report the somatic CNs of seventeen species from eight genera in Salicaceae. Of these, CNs for twelve species and for five genera are reported for the first time. Among the three subfamilies of Salicaceae, the available data indicate CN in Samydoideae is n = 21, 22, 42. The only two genera, Dianyuea and Scyphostegia, in Scyphostegioideae respectively have n = 9 and 18. In Salicoideae, Populus, Salix and five genera closely related to them (Bennettiodendron, Idesia, Carrierea, Poliothyrsis, Itoa) are based on relatively high CNs from n = 19, 20, 21, 22 to n = 95 in Salix. However, the other genera of Salicoideae are mainly based on relatively low CNs of n = 9, 10, 11. The genome sizes of 35 taxa belonging to 14 genera of Salicaceae were estimated. Of these, the genome sizes of 12 genera and all taxa except Populus euphratica are first reported. Except for Dianyuea, Idesia and Bennettiodendron, all examined species have relatively small genome sizes of less than 1 pg, although polyploidization exists. CONCLUSIONS: The variation of CN and genome size across Salicaceae indicates frequent ploidy changes and a widespread sharing of the salicoid whole genome duplication (WGD) by the relatives of Populus and Salix. The shrinkage of genome size after WGD indicates massive loss of genomic components. The phylogenetic asymmetry in clade of Populus, Salix, and their close relatives suggests that there is a lag-time for the subsequent radiations after the salicoid WGD event. Our results provide useful data for studying the evolutionary events of Salicaceae.

The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.

Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.

Congenital hypopituitarism in two brothers with a duplication of the 'acrogigantism gene' GPR101: clinical findings and review of the literature.

PURPOSE: Congenital hypopituitarism (CH) can cause significant morbidity or even mortality. In the majority of patients, the etiology of CH is unknown. Understanding the etiology of CH is important for anticipation of clinical problems and for genetic counselling. Our previous studies showed that only a small proportion of cases have mutations in the known 'CH genes'. In the current project, we present the results of SNP array based copy number variant analysis in a family with unexplained congenital hypopituitarism. METHODS: DNA samples of two affected brothers with idiopathic CH and their mother were simultaneously analyzed by SNP arrays for copy number variant analysis and Whole Exome Sequencing (WES) for mutation screening. DNA of the father was not available. RESULTS: We found a 6 Mb duplication including GPR101 and SOX3 on the X-chromosome (Xq26.2-q27.1) in the two siblings and their mother, leading to 2 copies of this region in the affected boys and 3 copies in the mother. Duplications of GPR101 are associated with X-linked acrogigantism (the phenotypic 'opposite' of the affected brothers), whereas alterations in SOX3 are associated with X-linked hypopituitarism. CONCLUSION: In our patients with hypopituitarism we found a 6 Mb duplication which includes GPR101, a gene associated with X- linked gigantism, and SOX3, a gene involved in early pituitary organogenesis that is associated with variable degrees of hypopituitarism. Our findings show that in duplications containing both GPR101 and SOX3, the growth hormone deficiency phenotype is dominant. This suggests that, if GPR101 is duplicated, it might not be expressed phenotypically when early patterning of the embryonic pituitary is affected due to SOX3 duplication. These results, together with the review of the literature, shed a new light on the role of GPR101 and SOX3 in pituitary function.

Copy number variants and fixed duplications among 198 rhesus macaques (Macaca mulatta).

The rhesus macaque is an abundant species of Old World monkeys and a valuable model organism for biomedical research due to its close phylogenetic relationship to humans. Copy number variation is one of the main sources of genomic diversity within and between species and a widely recognized cause of inter-individual differences in disease risk. However, copy number differences among rhesus macaques and between the human and macaque genomes, as well as the relevance of this diversity to research involving this nonhuman primate, remain understudied. Here we present a high-resolution map of sequence copy number for the rhesus macaque genome constructed from a dataset of 198 individuals. Our results show that about one-eighth of the rhesus macaque reference genome is composed of recently duplicated regions, either copy number variable regions or fixed duplications. Comparison with human genomic copy number maps based on previously published data shows that, despite overall similarities in the genome-wide distribution of these regions, there are specific differences at the chromosome level. Some of these create differences in the copy number profile between human disease genes and their rhesus macaque orthologs. Our results highlight the importance of addressing the number of copies of target genes in the design of experiments and cautions against human-centered assumptions in research conducted with model organisms. Overall, we present a genome-wide copy number map from a large sample of rhesus macaque individuals representing an important novel contribution concerning the evolution of copy number in primate genomes.

Exceptional diversity of opsin expression patterns in Neogonodactylus oerstedii (Stomatopoda) retinas.

Stomatopod crustaceans possess some of the most complex animal visual systems, including at least 16 spectrally distinct types of photoreceptive units (e.g., assemblages of photoreceptor cells). Here we fully characterize the set of opsin genes expressed in retinal tissues and determine expression patterns of each in the stomatopod Neogonodactylus oerstedii Using a combination of transcriptome and RACE sequencing, we identified 33 opsin transcripts expressed in each N. oerstedii eye, which are predicted to form 20 long-wavelength-sensitive, 10 middle-wavelength-sensitive, and three UV-sensitive visual pigments. Observed expression patterns of these 33 transcripts were highly unusual in five respects: 1) All long-wavelength and short/middle-wavelength photoreceptive units expressed multiple opsins, while UV photoreceptor cells expressed single opsins; 2) most of the long-wavelength photoreceptive units expressed at least one middle-wavelength-sensitive opsin transcript; 3) the photoreceptors involved in spatial, motion, and polarization vision expressed more transcripts than those involved in color vision; 4) there is a unique opsin transcript that is expressed in all eight of the photoreceptive units devoted to color vision; and 5) expression patterns in the peripheral hemispheres of the eyes suggest visual specializations not previously recognized in stomatopods. Elucidating the expression patterns of all opsin transcripts expressed in the N. oerstedii retina reveals the potential for previously undocumented functional diversity in the already complex stomatopod eye and is a first step toward understanding the functional significance of the unusual abundance of opsins found in many arthropod species' visual systems.

Identification, evolution and expression analyses of whole genome-wide TLP gene family in Brassica napus.

BACKGROUND: Brassica is a very important genus of Brassicaceae, including many important oils, vegetables, forage crops, and ornamental horticultural plants. TLP family genes play important regulatory roles in the growth and development of plants. Therefore, this study used a bioinformatics approach to conduct the systematic comparative genomics analysis of TLP gene family in B. napus and other three important Brassicaceae crops. RESULTS: Here, we identified a total of 29 TLP genes from B. napus genome, and they distributed on 16 chromosomes of B. napus. The evolutionary relationship showed that these genes could be divided into six groups from Group A to F. We found that the gene corresponding to Arabidopsis thaliana AT1G43640 was completely lost in B. rapa, B. oleracea and B. napus after whole genome triplication. The gene corresponding to AT1G25280 was retained in all the three species we analysed, belonging to 1:3:6 ratios. Our analyses suggested that there was a selective loss of some genes that might be redundant after genome duplication. This study proposed that the TLP genes in B. napus did not directly expansion compared with its diploid parents B. rapa, and B. oleracea. Instead, an indirect expansion of TLP gene family occurred in its two diploid parents. In addition, the study further utilized RNA-seq to detect the expression pattern of TLP genes between different tissues and two subgenomes. CONCLUSIONS: This study systematically conducted the comparative analyses of TLP gene family in B. napus, discussed the loss and expansion of genes after genome duplication. It provided rich gene resources for exploring the molecular mechanism of TLP gene family. Meanwhile, it provided guidance and reference for the research of other gene families in B. napus.

Characterizing lineage-specific evolution and the processes driving genomic diversification in chordates.

BACKGROUND: Understanding the origins of genome content has long been a goal of molecular evolution and comparative genomics. By examining genome evolution through the guise of lineage-specific evolution, it is possible to make inferences about the evolutionary events that have given rise to species-specific diversification. Here we characterize the evolutionary trends found in chordate species using The Adaptive Evolution Database (TAED). TAED is a database of phylogenetically indexed gene families designed to detect episodes of directional or diversifying selection across chordates. Gene families within the database have been assessed for lineage-specific estimates of dN/dS and have been reconciled to the chordate species to identify retained duplicates. Gene families have also been mapped to the functional pathways and amino acid changes which occurred on high dN/dS lineages have been mapped to protein structures. RESULTS: An analysis of this exhaustive database has enabled a characterization of the processes of lineage-specific diversification in chordates. A pathway level enrichment analysis of TAED determined that pathways most commonly found to have elevated rates of evolution included those involved in metabolism, immunity, and cell signaling. An analysis of protein fold presence on proteins, after normalizing for frequency in the database, found common folds such as Rossmann folds, Jelly Roll folds, and TIM barrels were overrepresented on proteins most likely to undergo directional selection. A set of gene families which experience increased numbers of duplications within short evolutionary times are associated with pathways involved in metabolism, olfactory reception, and signaling. An analysis of protein secondary structure indicated more relaxed constraint in ß-sheets and stronger constraint on alpha Helices, amidst a general preference for substitutions at exposed sites. Lastly a detailed analysis of the ornithine decarboxylase gene family, a key enzyme in the pathway for polyamine synthesis, revealed lineage-specific evolution along the lineage leading to Cetacea through rapid sequence evolution in a duplicate gene with amino acid substitutions causing active site rearrangement. CONCLUSION: Episodes of lineage-specific evolution are frequent throughout chordate species. Both duplication and directional selection have played large roles in the evolution of the phylum. TAED is a powerful tool for facilitating this understanding of lineage-specific evolution.

Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes.

The conservation of orthologs of most subunits of the origin recognition complex (ORC) has served to propose that the whole complex is common to all eukaryotes. However, various uncertainties have arisen concerning ORC subunit composition in a variety of lineages. Also, it is unclear whether the ancestral diversification of ORC in eukaryotes was accompanied by the neofunctionalization of some subunits, for example, role of ORC1 in centriole homeostasis. We have addressed these questions by reconstructing the distribution and evolutionary history of ORC1-5/CDC6 in a taxon-rich eukaryotic data set. First, we identified ORC subunits previously undetected in divergent lineages, which allowed us to propose a series of parsimonious scenarios for the origin of this multiprotein complex. Contrary to previous expectations, we found a global tendency in eukaryotes to increase or decrease the number of subunits as a consequence of genome duplications or streamlining, respectively. Interestingly, parasites show significantly lower number of subunits than free-living eukaryotes, especially those with the lowest genome size and gene content metrics. We also investigated the evolutionary origin of the ORC1 role in centriole homeostasis mediated by the PACT region in human cells. In particular, we tested the consequences of reducing ORC1 levels in the centriole-containing green alga Chlamydomonas reinhardtii. We found that the proportion of centrioles to flagella and nuclei was not dramatically affected. This, together with the PACT region not being significantly more conserved in centriole-bearing eukaryotes, supports the notion that this neofunctionalization of ORC1 would be a recent acquisition rather than an ancestral eukaryotic feature.

Allele specific expression of Dof genes responding to hormones and abiotic stresses in sugarcane.

Dof transcription factors plant-specific and associates with growth and development in plants. We conducted comprehensive and systematic analyses of Dof transcription factors in sugarcane, and identified 29 SsDof transcription factors in sugarcane genome. Those SsDof genes were divided into five groups, with similar gene structures and conserved motifs within the same groups. Segmental duplications are predominant in the evolution of Dof in sugarcane. Cis-element analysis suggested that the functions of SsDofs were involved in growth and development, hormones and abiotic stresses responses in sugarcane. Expression patterns indicated that SsDof7, SsDof23 and SsDof24 had a comparatively high expression in all detected tissues, indicating these genes are crucial in sugarcane growth and development. Moreover, we examined the transcription levels of SsDofs under four plant hormone treatments, SsDof7-3 and SsDof7-4 were down-regulated after ABA treatment, while SsDof7-1 and SsDof7-2 were induced after the same treatment, indicating different alleles may play different roles in response to plant hormones. We also analyzed SsDofs' expression profiling under four abiotic stresses, SsDof5 and SsDof28 significantly responded to these four stresses, indicating they are associate with abiotic stresses responses. Collectively, our results yielded allele specific expression of Dof genes responding to hormones and abiotic stresses in sugarcane, and their cis-elements could be crucial for sugarcane improvement.

Evolution of the RNA N 6-Methyladenosine Methylome Mediated by Genomic Duplication.

RNA N 6-methyladenosine (m6A) modification is the most abundant form of RNA epigenetic modification in eukaryotes. Given that m6A evolution is associated with the selective constraints of nucleotide sequences in mammalian genomes, we hypothesize that m6A evolution can be linked, at least in part, to genomic duplication events in complex polyploid plant genomes. To test this hypothesis, we presented the maize (Zea mays) m6A modification landscape in a transcriptome-wide manner and identified 11,968 m6A peaks carried by 5,893 and 3,811 genes from two subgenomes (maize1 and maize2, respectively). Each of these subgenomes covered over 2,200 duplicate genes. Within these duplicate genes, those carrying m6A peaks exhibited significant differences in retention rate. This biased subgenome fractionation of m6A-methylated genes is associated with multiple sequence features and is influenced by asymmetric evolutionary rates. We also characterized the coevolutionary patterns of m6A-methylated genes and transposable elements, which can be mediated by whole genome duplication and tandem duplication. We revealed the evolutionary conservation and divergence of duplicated m6A functional factors and the potential role of m6A modification in maize responses to drought stress. This study highlights complex interplays between m6A modification and gene duplication, providing a reference for understanding the mechanisms underlying m6A evolution mediated by genome duplication events.

Neutral evolution of cellular phenotypes.

Eukaryotes exhibit a great diversity of cellular and subcellular morphologies, but their basic underlying architecture is fairly constant. All have a nucleus, Golgi, cytoskeleton, plasma membrane, vesicles, ribosomes, and all known lineages but one have mitochondrion-related organelles. Moreover, most eukaryotes undergo processes such as mitosis, meiosis, DNA recombination, and often perform feats such as phagocytosis, and amoeboid and flagellar movement. With all of these commonalities, it is obvious that eukaryotes evolved from a common ancestor, but it is not obvious how eukaryotes came to have their diverse structural phenotypes. Are these phenotypes adaptations to particular niches, their evolution dominated by positive natural selection? Or is eukaryotic cellular diversity substantially the product of neutral evolutionary processes, with adaptation either illusory or a secondary consequence? In this paper, we outline how a hierarchical view of phenotype can be used to articulate a neutral theory of phenotypic evolution, involving processes such as gene loss, gene replacement by homologues or analogues, gene duplication followed by subfunctionalization, and constructive neutral evolution. We suggest that neutral iterations of these processes followed by entrenchment of their products can explain much of the diversity of cellular, developmental, and biochemical phenotypes of unicellular eukaryotes and should be explored in addition to adaptive explanations.

Human core duplicon gene families: game changers or game players?

Illuminating the role of specific gene duplications within the human lineage can provide insights into human-specific adaptations. The so-called human core duplicon gene families have received particular attention in this respect, due to special features, such as expansion along single chromosomes, newly acquired protein domains and signatures of positive selection. Here, we summarize the data available for 10 such families and include some new analyses. A picture emerges that suggests broad functions for these protein families, possibly through modification of core cellular pathways. Still, more dedicated studies are required to elucidate the function of core-duplicons gene families and how they have shaped adaptations and evolution of humans.

Redundant SCARECROW genes pattern distinct cell layers in roots and leaves of maize.

The highly efficient C4 photosynthetic pathway is facilitated by 'Kranz' leaf anatomy. In Kranz leaves, closely spaced veins are encircled by concentric layers of photosynthetic bundle sheath (inner) and mesophyll (outer) cells. Here, we demonstrate that, in the C4 monocot maize, Kranz patterning is regulated by redundant function of SCARECROW 1 (ZmSCR1) and a previously uncharacterized homeologue: ZmSCR1h. ZmSCR1 and ZmSCR1h transcripts accumulate in ground meristem cells of developing leaf primordia and in Zmscr1;Zmscr1h mutant leaves, most veins are separated by one rather than two mesophyll cells; many veins have sclerenchyma above and/or below instead of mesophyll cells; and supernumerary bundle sheath cells develop. The mutant defects are unified by compromised mesophyll cell development. In addition to Kranz defects, Zmscr1;Zmscr1h mutants fail to form an organized endodermal layer in the root. Collectively, these data indicate that ZmSCR1 and ZmSCR1h redundantly regulate cell-type patterning in both the leaves and roots of maize. Leaf and root pathways are distinguished, however, by the cell layer in which they operate - mesophyll at a two-cell distance from leaf veins versus endodermis immediately adjacent to root vasculature.

Duplication of a domestication locus neutralized a cryptic variant that caused a breeding barrier in tomato.

Genome editing technologies are being widely adopted in plant breeding1. However, a looming challenge of engineering desirable genetic variation in diverse genotypes is poor predictability of phenotypic outcomes due to unforeseen interactions with pre-existing cryptic mutations2-4. In tomato, breeding with a classical MADS-box gene mutation that improves harvesting by eliminating fruit stem abscission frequently results in excessive inflorescence branching, flowering and reduced fertility due to interaction with a cryptic variant that causes partial mis-splicing in a homologous gene5-8. Here, we show that a recently evolved tandem duplication carrying the second-site variant achieves a threshold of functional transcripts to suppress branching, enabling breeders to neutralize negative epistasis on yield. By dissecting the dosage mechanisms by which this structural variant restored normal flowering and fertility, we devised strategies that use CRISPR-Cas9 genome editing to predictably improve harvesting. Our findings highlight the under-appreciated impact of epistasis in targeted trait breeding and underscore the need for a deeper characterization of cryptic variation to enable the full potential of genome editing in agriculture.

Translocation of promoter-conserved hatching enzyme genes with intron-loss provides a new insight in the role of retrocopy during teleostean evolution.

The hatcing enzyme gene (HE) encodes a protease that is indispensable for the hatching process and is conserved during vertebrate evolution. During teleostean evolution, it is known that HE experienced a drastic transfiguration of gene structure, namely, losing all of its introns. However, these facts are contradiction with each other, since intron-less genes typically lose their original promoter because of duplication via mature mRNA, called retrocopy. Here, using a comparative genomic assay, we showed that HEs have changed their genomic location several times, with the evolutionary timings of these translocations being identical to those of intron-loss. We further showed that HEs maintain the promoter sequence upstream of them after translocation. Therefore, teleostean HEs are unique genes which have changed intra- (exon-intron) and extra-genomic structure (genomic loci) several times, although their indispensability for the reproductive process of hatching implies that HE genes are translocated by retrocopy with their promoter sequence.

Functional Characterization and Evolutionary Analysis of Glycine-Betaine Biosynthesis Pathway in Red Seaweed Pyropia yezoensis.

The red seaweed Pyropia yezoensis is an ideal research model for dissecting the molecular mechanisms underlying its robust acclimation to abiotic stresses in intertidal zones. Glycine betaine (GB) was an important osmolyte in maintaining osmotic balance and stabilizing the quaternary structure of complex proteins under abiotic stresses (drought, salinity, etc.) in plants, animals, and bacteria. However, the existence and possible functions of GB in Pyropia remain elusive. In this study, we observed the rapid accumulation of GB in desiccated Pyropia blades, identifying its essential roles in protecting Pyropia cells against severe osmotic stress. Based on the available genomic and transcriptomic information of Pyropia, we computationally identified genes encoding the three key enzymes in the GB biosynthesis pathway: phosphoethanolamine N-methyltransferase (PEAMT), choline dehydrogenase (CDH), and betaine aldehyde dehydrogenase (BADH). Pyropia had an extraordinarily expanded gene copy number of CDH (up to seven) compared to other red algae. Phylogeny analysis revealed that in addition to the one conservative CDH in red algae, the other six might have originated from early gene duplication events. In dehydration stress, multiple CDH paralogs and PEAMT genes were coordinating up-regulated and shunted metabolic flux into GB biosynthesis. An elaborate molecular mechanism might be involved in the transcriptional regulation of these genes.

Spontaneous Changes in Ploidy Are Common in Yeast.

Changes in ploidy are relatively rare, but play important roles in the development of cancer and the acquisition of long-term adaptations. Genome duplications occur across the tree of life, and can alter the rate of adaptive evolution. Moreover, by allowing the subsequent loss of individual chromosomes and the accumulation of mutations, changes in ploidy can promote genomic instability and/or adaptation. Although many studies have been published in the last years about changes in chromosome number and their evolutionary consequences, tracking and measuring the rate of whole-genome duplications have been extremely challenging. We have systematically studied the appearance of diploid cells among haploid yeast cultures evolving for over 100 generations in different media. We find that spontaneous diploidization is a relatively common event, which is usually selected against, but under certain stressful conditions may become advantageous. Furthermore, we were able to detect and distinguish between two different mechanisms of diploidization, one that requires whole-genome duplication (endoreduplication) and a second that involves mating-type switching despite the use of heterothallic strains. Our results have important implications for our understanding of evolution and adaptation in fungal pathogens and the development of cancer, and for the use of yeast cells in biotechnological applications.

The unique evolutionary pattern of the Hydroxyproline-rich glycoproteins superfamily in Chinese white pear (Pyrus bretschneideri).

BACKGROUND: The hydroxyproline-rich glycoprotein (HRGP) superfamily, comprising three families (arabinogalactan-proteins, AGPs; extensins, EXTs; proline-rich proteins, PRPs), is a class of proline-rich proteins that exhibit high diversity and are involved in many aspects of plant biology. RESULTS: In this study, 838 HRGPs were identified from Chinese white pear (Pyrus bretschneideri) by searching for biased amino acid composition and conserved motifs. 405 HRGPs were derived from whole genome duplication (WGD) events which is suggested to be the major force of driving HRGPs expansion and the recent WGD event shared by apple and pear generated most duplicated HRGPs in pear. This duplication event drived the structural variation of the HRGPs encoding hydroxyproline (Hyp)-rich motifs. The rate of HRGPs evolution mainly impacted the Hyp-rich motifs even in chimeric HRGPs. During the evolution of 53 PRPs that are also typified by 7-deoxyloganetin glucosyltransferase-like genes, the duplication from PRP to non-PRP was indirectly modified by positive selection. These results suggested that the rate of HRGP evolution mainly influenced the Hyp-rich motifs even in chimeric HRGPs. The expression divergence of HRGPs was higher than that of other commonly duplicated genes. In pear pistil, 601 HRGPs exhibited expression, while in pear pollen, 285 HRGPs were expressed. The qPCR results revealed that Pbr036330.1 and Pbr010506.1 showed different expression profile in self-incompatibility of pear pistil. CONCLUSIONS: The researches indicated that WGD events was the main duplication type during the evolution of HRGPs, and the highly variable Hyp-motifs might be accountable for the expansion, evolution and expression divergence of HRGPs and that this divergence may be responsible for the gain of new functions in plants.

Faster Evolving Primate Genes Are More Likely to Duplicate.

An attractive and long-standing hypothesis regarding the evolution of genes after duplication posits that the duplication event creates new evolutionary possibilities by releasing a copy of the gene from constraint. Apparent support was found in numerous analyses, particularly, the observation of higher rates of evolution in duplicated as compared with singleton genes. Could it, instead, be that more duplicable genes (owing to mutation, fixation, or retention biases) are intrinsically faster evolving? To uncouple the measurement of rates of evolution from the determination of duplicate or singleton status, we measure the rates of evolution in singleton genes in outgroup primate lineages but classify these genes as to whether they have duplicated or not in a crown group of great apes. We find that rates of evolution are higher in duplicable genes prior to the duplication event. In part this is owing to a negative correlation between coding sequence length and rate of evolution, coupled with a bias toward smaller genes being more duplicable. The effect is masked by difference in expression rate between duplicable genes and singletons. Additionally, in contradiction to the classical assumption, we find no convincing evidence for an increase in dN/dS after duplication, nor for rate asymmetry between duplicates. We conclude that high rates of evolution of duplicated genes are not solely a consequence of the duplication event, but are rather a predictor of duplicability. These results are consistent with a model in which successful gene duplication events in mammals are skewed toward events of minimal phenotypic impact.

Accessing the Phenotype Gap: Enabling Systematic Investigation of Paralog Functional Complexity with CRISPR.

Single-gene knockout experiments can fail to reveal function in the context of redundancy, which is frequently observed among duplicated genes (paralogs) with overlapping functions. We discuss the complexity associated with studying paralogs and outline how recent advances in CRISPR will help address the "phenotype gap" and impact biomedical research.