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Previous studies have shown that recombination between allelic sequences can cause likelihood-based methods for detecting positive selection to produce many false-positive results. In this article, we use simulations to study the impact of nonallelic gene conversion on the specificity of PAML to detect positive selection among gene duplicates. Our results show that, as expected, gene conversion leads to higher rates of false-positive results, although only moderately. These rates increase with the genetic distance between sequences, the length of converted tracts, and when no outgroup sequences are included in the analysis. We also find that branch-site models will incorrectly identify unconverted sequences as the targets of positive selection when their close paralogs are converted. Bayesian prediction of sites undergoing adaptive evolution implemented in PAML is affected by conversion, albeit in a less straightforward way. Our work suggests that particular attention should be devoted to the evolutionary analysis of recent duplicates that may have experienced gene conversion because they may provide false signals of positive selection. Fortunately, these results also imply that those cases most susceptible to false-positive results--i.e., high divergence between paralogs, long conversion tracts--are also the cases where detecting gene conversion is the easiest.

Gene conversion between duplicated genes has been implicated in homogenization of gene families and reassortment of variation among paralogs. If conversion is common, this process could lead to errors in gene tree inference and subsequent overestimation of rates of gene duplication. After performing simulations to assess our power to detect gene conversion events, we determined rates of conversion among young, lineage-specific gene duplicates in four mammal species: human, rhesus macaque, mouse, and rat. Gene conversion rates (number of conversion events/number of gene pairs) among young duplicates range from 8.3% in macaque to 18.96% in rat, including a 5% false-positive rate. For all lineages, only 1-3% of the total amount of sequence examined was converted. There is no increase in GC content in conversion tracts compared to flanking regions of the same genes nor in conversion tracts compared to the same region in nonconverted gene-family members, suggesting that ectopic gene conversion does not significantly alter nucleotide composition in these duplicates. While the majority of gene duplicate pairs reside on different chromosomes in mammalian genomes, the majority of gene conversion events occur between duplicates on the same chromosome, even after controlling for divergence between duplicates. Among intrachromosomal duplicates, however, there is no correlation between the probability of conversion and physical distance between duplicates after controlling for divergence. Finally, we use a novel method to show that at most 5-10% of all gene trees involving young duplicates are likely to be incorrect due to gene conversion. We conclude that gene conversion has had only a small effect on mammalian genomes and gene duplicate evolution in general.

Duplicate genes act as a source of genetic material from which new functions arise. They exist in large numbers in every sequenced eukaryotic genome and may be responsible for many differences in phenotypes between species. However, recent work searching for the targets of positive selection in humans has largely ignored duplicated genes due to complications in orthology assignment. Here we find that a high proportion of young gene duplicates in the human, macaque, mouse, and rat genomes have experienced adaptive natural selection. Approximately 10% of all lineage-specific duplicates show evidence for positive selection on their protein sequences, larger than any reported amount of selection among single-copy genes in these lineages using similar methods. We also find that newly duplicated genes that have been transposed to new chromosomal locations are significantly more likely to have undergone positive selection than the ancestral copy. Human-specific duplicates evolving under adaptive natural selection include a surprising number of genes involved in neuronal and cognitive functions. Our results imply that genome scans for selection that ignore duplicated loci are missing a large fraction of all adaptive substitutions. The results are also in agreement with the classical model of evolution by gene duplication, supporting a common role for neofunctionalization in the long-term maintenance of gene duplicates.

Retrogenes are processed copies of genes that are inserted into new genomic regions and that acquire new regulatory elements from the sequences in their surroundings. Here we use a comparative approach of phylogenetic footprinting and a non-comparative approach of measuring motif over-representation in retrogenes in order to describe putative elements present in cis-regulatory regions of 94 retrogenes recently described in Drosophila. The detailed examination of the motifs found in the core promoter regions of retrogenes reveals an abundance of the DNA replication-related element (DRE), the Initiator (Inr), and a new over-represented motif that we call the GCT motif. Parental genes also show an abundance of DRE and Inr motifs, but these do not seem to have been carried over with retrogenes. In particular, we also examined motifs upstream of retrogenes expressed in adult testis and were able to identify 6 additional over-represented motifs. Comparative analyses provide data on the conservation and origin of some of these motifs and reveal 15 additional conserved motifs in these retrogenes. Some of those conserved motifs are sequences bound by known transcription factors, while others are novel motifs. In this report we provide the first genome-wide data on which specific cis-regulatory regions can be recruited by retrogenes after they are inserted into new coding regions in the genome. Future experiments are needed to determine the function and role of the new elements presented here.

Background: Retrogenes are processed copies of other genes. This duplication mechanism produces a copy of the parental gene that should not contain introns, and usually does not contain cis-regulatory regions. Here, we computationally address the evolutionary origin of promoter and other cis-regulatory regions in retrogenes using a total of 94 Drosophila retroposition events we recently identified. Previous tissue expression data has revealed that a large fraction of these retrogenes are specifically and/or highly expressed in adult testes of Drosophila., Results: In this work, we infer that retrogenes do not generally carry regulatory regions from aberrant upstream or normal transcripts of their parental genes, and that expression patterns of neighboring genes are not consistently shared by retrogenes. Additionally, transposable elements do not appear to substantially provide regulatory regions to retrogenes. Interestingly, we find that there is an excess of retrogenes in male testis neighborhoods that is not explained by insertional biases of the retroelement machinery used for retroposition., Conclusion: We conclude that retrogenes' regulatory regions mostly do not represent a random set of existing regulatory regions. On the contrary, our conclusion is that selection is likely to have played an important role in the persistence of autosomal testis biased retrogenes. Selection in favor of retrogenes inserted in male testis neighborhoods and at the sequence level to produce testis expression is postulated to have occurred.

The mammalian centromere-associated protein B (CENP-B) shares significant sequence similarity with 3 proteins in fission yeast (Abp1, Cbh1, and Cbh2) that also bind centromeres and have essential function for chromosome segregation and centromeric heterochromatin formation. Each of these proteins displays extensive sequence similarity with pogo-like transposases, which have been previously identified in the genomes of various insects and vertebrates, in the protozoan Entamoeba and in plants. Based on this distribution, it has been proposed that the mammalian and fission yeast centromeric proteins are derived from "domesticated" pogo-like transposons. Here we took advantage of the vast amount of sequence information that has become recently available for a wide range of fungal and animal species to investigate the origin of the mammalian CENP-B and yeast CENP-B-like genes. A highly conserved ortholog of CENP-B was detected in 31 species of mammals, including opossum and platypus, but was absent from all nonmammalian species represented in the databases. Similarly, no ortholog of the fission yeast centromeric proteins was identified in any of the various fungal genomes currently available. In contrast, we discovered a plethora of novel pogo-like transposons in diverse invertebrates and vertebrates and in several filamentous fungi. Phylogenetic analysis revealed that the mammalian and fission yeast CENP-B proteins fall into 2 distinct monophyletic clades, each of which includes a different set of pogo-like transposons. These results are most parsimoniously explained by independent domestication events of pogo-like transposases into centromeric proteins in the mammalian and fission yeast lineages, a case of "convergent domestication." These findings highlight the propensity of transposases to give rise to new host proteins and the potential of transposons as sources of genetic innovation.

Plants use light to optimize growth and development. The photoreceptor phytochrome A (phyA) mediates various far-red light-induced responses. We show that Arabidopsis FHY3 and FAR1, which encode two proteins related to Mutator-like transposases, act together to modulate phyA signaling by directly activating the transcription of FHY1 and FHL, whose products are essential for light-induced phyA nuclear accumulation and subsequent light responses. FHY3 and FAR1 have separable DNA binding and transcriptional activation domains that are highly conserved in Mutator-like transposases. Further, expression of FHY3 and FAR1 is negatively regulated by phyA signaling. We propose that FHY3 and FAR1 represent transcription factors that have been co-opted from an ancient Mutator-like transposase(s) to modulate phyA-signaling homeostasis in higher plants.

Germline cell fate decisions are primarily controlled at the post-transcriptional level with DEAD-box RNA helicases playing a crucial role in germline development. In this study, we report the identification of two DEAD-box vasa/PL10 orthologues (RlVlg and RlPL10) in a species complex of the genus Rana, characterized by hybridogenetic reproduction, an enigmatic process that involves the exclusion of an individual genome, and endoreduplication events. Both genes were expressed during the early stages of gametogenesis of R. ridibunda, R. lessonae, and their natural hybrid R. esculenta. RlVlg expression was germline specific. On the other hand, RlPL10 was also expressed in somatic tissues, although only at low levels. The two genes were expressed in different phases of mitotic and meiotic spermatogenetic divisions as demonstrated by immunostaining with an anti-H3 phosphohistone antibody. The data indicate that RlVlg and RlPL10 may represent useful markers for dissecting the molecular aspects of genome exclusion and endoreduplication of the hybridogenetic gametogenesis.

European water frog hybrids Rana esculenta (R. ridibundaxR. lessonae) reproduce hemiclonally, by hybridogenesis: in the germ line they exclude the genome of one parental species and produce haploid gametes with an unrecombined genome of the other parental species. In the widespread L-E population system, both sexes of hybrids (E) coexist with R. lessonae (L). They exclude the lessonae genome and produce ridibunda gametes. In the R-E system, hybrid males coexist with R. ridibunda (R); they exclude either their ridibunda or their lessonae genome and produce sperm with a lessonae or with a ridibunda genome or a mixture of both kinds of sperm. We examined 13 male offspring, 12 of which were from crosses between L-E system and R-E system frogs. All were somatically hybrid. With one exception, they excluded the lessonae genome in the germ line and subsequently endoreduplicated the ridibunda genome. Spermatogonial metaphases contained a haploid or a diploid number of ridibunda chromosomes, identified through in situ hybridization to a satellite DNA marker, and by spermatocyte I metaphases containing a haploid number of ridibunda bivalents. The exception, an F1 hybrid between L-E system R. lessonae and R-E system R. ridibunda, was not hybridogenetic, showed no genome exclusion, and evidenced a disturbed gametogenesis resulting from the combination of two heterospecific genomes. None of the hybridogenetic hybrids showed any cell lines excluding the ridibunda genome, the pattern most frequent in hybrids of the R-E system, unique to that system, and essential for its persistence. A particular combination of R-E system lessonae and R-E system ridibunda genomes seems necessary to induce the R-E system type of hemiclonal gametogenesis.

Background: Processed copies of genes (retrogenes) are duplicate genes that originated through the reverse-transcription of a host transcript and insertion in the genome. This type of gene duplication, as any other, could be a source of new genes and functions. Using whole genome sequence data for 12 Drosophila species, we dated the origin of 94 retroposition events that gave rise to candidate functional genes in D. melanogaster., Results: Based on this analysis, we infer that functional retrogenes have emerged at a fairly constant rate of 0.5 genes per million years per lineage over the last approximately 63 million years of Drosophila evolution. The number of functional retrogenes and the rate at which they are recruited in the D. melanogaster lineage are of the same order of magnitude as those estimated in the human lineage, despite the higher deletion bias in the Drosophila genome. However, unlike primates, the rate of retroposition in Drosophila seems to be fairly constant and no burst of retroposition can be inferred from our analyses. In addition, our data also support an important role for retrogenes as a source of lineage-specific male functions, in agreement with previous hypotheses. Finally, we identified three cases of functional retrogenes in D. melanogaster that have been independently retroposed and recruited in parallel as new genes in other Drosophila lineages., Conclusion: Together, these results indicate that retroposition is a persistent mechanism and a recurrent pathway for the emergence of new genes in Drosophila.