Young Genes Research Articles

Rapid Intraspecies Evolution of Fitness Effects of Yeast Genes.

Organisms within species have numerous genetic and phenotypic variations. Growing evidences show intraspecies variation of mutant phenotypes may be more complicated than expected. Current studies on intraspecies variations of mutant phenotypes are limited to just a few strains. This study investigated the intraspecies variation of fitness effects of 5,630 gene mutants in ten Saccharomyces cerevisiae strains using CRISPR–Cas9 screening. We found that the variability of fitness effects induced by gene disruptions is very large across different strains. Over 75% of genes affected cell fitness in a strain-specific manner to varying degrees. The strain specificity of the fitness effect of a gene is related to its evolutionary and functional properties. Subsequent analysis revealed that younger genes, especially those newly acquired in S. cerevisiae species, are more likely to be strongly strain-specific. Intriguingly, there seems to exist a ceiling of fitness effect size for strong strain-specific genes, and among them, the newly acquired genes are still evolving and have yet to reach this ceiling. Additionally, for a large proportion of protein complexes, the strain specificity profile is inconsistent among genes encoding the same complex. Taken together, these results offer a genome-wide map of intraspecies variation for fitness effect as a mutant phenotype and provide an updated insight on intraspecies phenotypic evolution.

Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse.

Although the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.

Transcription Factors Drive Opposite Relationships between Gene Age and Tissue Specificity in Male and Female Drosophila Gonads.

Evolutionarily young genes are usually preferentially expressed in the testis across species. Although it is known that older genes are generally more broadly expressed than younger genes, the properties that shaped this pattern are unknown. Older genes may gain expression across other tissues uniformly, or faster in certain tissues than others. Using Drosophila gene expression data, we confirmed previous findings that younger genes are disproportionately testis biased and older genes are disproportionately ovary biased. We found that the relationship between gene age and expression is stronger in the ovary than any other tissue and weakest in testis. We performed ATAC-seq on Drosophila testis and found that although genes of all ages are more likely to have open promoter chromatin in testis than in ovary, promoter chromatin alone does not explain the ovary bias of older genes. Instead, we found that upstream transcription factor (TF) expression is highly predictive of gene expression in ovary but not in testis. In the ovary, TF expression is more predictive of gene expression than open promoter chromatin, whereas testis gene expression is similarly influenced by both TF expression and open promoter chromatin. We propose that the testis is uniquely able to express younger genes controlled by relatively few TFs, whereas older genes with more TF partners are broadly expressed with peak expression most likely in the ovary. The testis allows widespread baseline expression that is relatively unresponsive to regulatory changes, whereas the ovary transcriptome is more responsive to trans-regulation and has a higher ceiling for gene expression.

Hypothesis: protein and RNA attributes are continuously optimized over time

BackgroundLittle is known why proteins and RNAs exhibit half-lives varying over several magnitudes. Despite many efforts, a conclusive link between half-lives and gene function could not be established suggesting that other determinants may influence these molecular attributes.ResultsHere, I find that with increasing gene age there is a gradual and significant increase of protein and RNA half-lives, protein structure, and other molecular attributes that tend to affect protein abundance. These observations are accommodated in a hypothesis which posits that new genes at ‘birth’ are not optimized and thus their products exhibit low half-lives and less structure but continuous mutagenesis eventually improves these attributes. Thus, the protein and RNA products of the oldest genes obtained their high degrees of stability and structure only after billions of years while the products of younger genes had less time to be optimized and are therefore less stable and structured. Because more stable proteins with lower turnover require less transcription to maintain the same level of abundance, reduced transcription-associated mutagenesis (TAM) would fixate the changes by increasing gene conservation.ConclusionsConsequently, the currently observed diversity of molecular attributes is a snapshot of gene products being at different stages along their temporal path of optimization.

Topological evolution of coexpression networks by new gene integration maintains the hierarchical and modular structures in human ancestors.

We analyze the global structure and evolution of human gene coexpression networks driven by new gene integration. When the Pearson correlation coefficient is greater than or equal to 0.5, we find that the coexpression network consists of 334 small components and one "giant" connected subnet comprising of 6317 interacting genes. This network shows the properties of power-law degree distribution and small-world. The average clustering coefficient of younger genes is larger than that of the elderly genes (0.6685 vs. 0.5762). Particularly, we find that the younger genes with a larger degree also show a property of hierarchical architecture. The younger genes play an important role in the overall pivotability of the network and this network contains few redundant duplicate genes. Moreover, we find that gene duplication and orphan genes are two dominant evolutionary forces in shaping this network. Both the duplicate genes and orphan genes develop new links through a "rich-gets-richer" mechanism. With the gradual integration of new genes into the ancestral network, most of the topological structure features of the network would gradually increase. However, the exponent of degree distribution and modularity coefficient of the whole network do not change significantly, which implies that the evolution of coexpression networks maintains the hierarchical and modular structures in human ancestors.

Phylogenomic analysis of gene co-expression networks reveals the evolution of functional modules.

Molecular evolutionary studies correlate genomic and phylogenetic information with the emergence of new traits of organisms. These traits are, however, the consequence of dynamic gene networks composed of functional modules, which might not be captured by genomic analyses. Here, we established a method that combines large-scale genomic and phylogenetic data with gene co-expression networks to extensively study the evolutionary make-up of modules in the moss Physcomitrella patens, and in the angiosperms Arabidopsis thaliana and Oryza sativa (rice). We first show that younger genes are less annotated than older genes. By mapping genomic data onto the co-expression networks, we found that genes from the same evolutionary period tend to be connected, whereas old and young genes tend to be disconnected. Consequently, the analysis revealed modules that emerged at a specific time in plant evolution. To uncover the evolutionary relationships of the modules that are conserved across the plant kingdom, we added phylogenetic information that revealed duplication and speciation events on the module level. This combined analysis revealed an independent duplication of cell wall modules in bryophytes and angiosperms, suggesting a parallel evolution of cell wall pathways in land plants. We provide an online tool allowing plant researchers to perform these analyses at http://www.gene2function.de.

Komplementation von Genexpressionsmustern in Maishybriden

Heterosis describes the superior performance of F1-hybrids compared to their genetically distinct parents, a phenomenon which is extensively exploited in maize breeding. To better understand the molecular basis of heterosis in maize, we analyzed how the genetic diversity of parental inbred lines affects the root transcriptome of their F1-progeny. We discovered complementation of activity in evolutionary younger genes and as a consequence more active genes in hybrids than in parental inbred lines.

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions.

Phylogenetic patterns of emergence of new genes support a model of frequent de novo evolution

BackgroundNew gene emergence is so far assumed to be mostly driven by duplication and divergence of existing genes. The possibility that entirely new genes could emerge out of the non-coding genomic background was long thought to be almost negligible. With the increasing availability of fully sequenced genomes across broad scales of phylogeny, it has become possible to systematically study the origin of new genes over time and thus revisit this question.ResultsWe have used phylostratigraphy to assess trends of gene evolution across successive phylogenetic phases, using mostly the well-annotated mouse genome as a reference. We find several significant general trends and confirm them for three other vertebrate genomes (humans, zebrafish and stickleback). Younger genes are shorter, both with respect to gene length, as well as to open reading frame length. They contain also fewer exons and have fewer recognizable domains. Average exon length, on the other hand, does not change much over time. Only the most recently evolved genes have longer exons and they are often associated with active promotor regions, i.e. are part of bidirectional promotors. We have also revisited the possibility that de novo evolution of genes could occur even within existing genes, by making use of an alternative reading frame (overprinting). We find several cases among the annotated Ensembl ORFs, where the new reading frame has emerged at a higher phylostratigraphic level than the original one. We discuss some of these overprinted genes, which include also the Hoxa9 gene where an alternative reading frame covering the homeobox has emerged within the lineage leading to rodents and primates (Euarchontoglires).ConclusionsWe suggest that the overall trends of gene emergence are more compatible with a de novo evolution model for orphan genes than a general duplication-divergence model. Hence de novo evolution of genes appears to have occurred continuously throughout evolutionary time and should therefore be considered as a general mechanism for the emergence of new gene functions.

Younger Genes Are Less Likely to Be Essential than Older Genes, and Duplicates Are Less Likely to Be Essential than Singletons of the Same Age

Recently duplicated genes are believed to often overlap in function and expression. A priori, they are thus less likely to be essential. Although this was indeed observed in yeast, mouse singletons and duplicates were reported to be equally often essential. This contradiction can only partly be explained by experimental biases. We herein show that older genes (i.e., genes with earlier phyletic origin) are more likely to be essential, regardless of their duplication status. At a given phyletic gene age, duplicates are always less likely to be essential compared with singletons. The “paradoxical” high essentiality among mouse gene duplicates is then caused by different age profiles of singletons and duplicates, with the latter tending to be derived from older genes.

Relaxed Purifying Selection and Possibly High Rate of Adaptation in Primate Lineage-Specific Genes

Genes in the same organism vary in the time since their evolutionary origin. Without horizontal gene transfer, young genes are necessarily restricted to a few closely related species, whereas old genes can be broadly distributed across the phylogeny. It has been shown that young genes evolve faster than old genes; however, the evolutionary forces responsible for this pattern remain obscure. Here, we classify human–chimp protein-coding genes into different age classes, according to the breath of their phylogenetic distribution. We estimate the strength of purifying selection and the rate of adaptive selection for genes in different age classes. We find that older genes carry fewer and less frequent nonsynonymous single-nucleotide polymorphisms than younger genes suggesting that older genes experience a stronger purifying selection at the protein-coding level. We infer the distribution of fitness effects of new deleterious mutations and find that older genes have proportionally more slightly deleterious mutations and fewer nearly neutral mutations than younger genes. To investigate the role of adaptive selection of genes in different age classes, we determine the selection coefficient (γ = 2Nes) of genes using the MKPRF approach and estimate the ratio of the rate of adaptive nonsynonymous substitution to synonymous substitution (ωA) using the DoFE method. Although the proportion of positively selected genes (γ > 0) is significantly higher in younger genes, we find no correlation between ωA and gene age. Collectively, these results provide strong evidence that younger genes are subject to weaker purifying selection and more tenuous evidence that they also undergo adaptive evolution more frequently.

MOVILIDAD SOCIAL INTERGENERACIONAL POR ORIGEN ÉTNICO: EVIDENCIA EMPÍRICA REGIÓN DE LA ARAUCANÍA, CHILE

The study shows that Araucania Region has a significant social intergenerational rate of mobility, related to higher educational achievements on younger gene...

Transcribed Tc1-like transposons in salmonid fish

BackgroundMobile genetic elements comprise a substantial fraction of vertebrate genomes. These genes are considered to be deleterious, and in vertebrates they are usually inactive. High throughput sequencing of salmonid fish cDNA libraries has revealed a large number of transposons, which remain transcribed despite inactivation of translation. This article reports on the structure and potential role of these genes.ResultsA search of EST showed the ratio of transcribed transposons in salmonid fish (i.e., 0.5% of all unique cDNA sequences) to be 2.4–32 times greater than in other vertebrate species, and 68% of these genes belonged to the Tc1-family of DNA transposons. A phylogenetic analysis of reading frames indicate repeated transposition of distantly related genes into the fish genome over protracted intervals of evolutionary time. Several copies of two new DNA transposons were cloned. These copies showed relatively little divergence (11.4% and 1.9%). The latter gene was transcribed at a high level in rainbow trout tissues, and was present in genomes of many phylogenetically remote fish species. A comparison of synonymous and non-synonymous divergence revealed remnants of divergent evolution in the younger gene, while the older gene evolved in a neutral mode. From a 1.2 MB fragment of genomic DNA, the salmonid genome contains approximately 105 Tc1-like sequences, the major fraction of which is not transcribed. Our microarray studies showed that transcription of rainbow trout transposons is activated by external stimuli, such as toxicity, stress and bacterial antigens. The expression profiles of Tc1-like transposons gave a strong correlation (r2 = 0.63–0.88) with a group of genes implicated in defense response, signal transduction and regulation of transcription.ConclusionSalmonid genomes contain a large quantity of transcribed mobile genetic elements. Divergent or neutral evolution within genomes and lateral transmission can account for the diversity and sustained persistence of Tc1-like transposons in lower vertebrates. A small part of transposons remain transcribed and their transcription is enhanced by responses to acute conditions.