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The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes' 1-3 , with a proposed role in contributing to human bipedalism 4-6 . Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene 7-9 -pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans 10 . Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today., (© 2024. The Author(s).)

The evolution of development has been studied through the lens of gene regulation by examining either closely related species or extremely distant animals of different phyla. In nematodes, detailed cell- and stage-specific expression analyses are focused on the model Caenorhabditis elegans , in part leading to the view that the developmental expression of gene cascades in this species is archetypic for the phylum. Here, we compared two species of an intermediate evolutionary distance: the nematodes C. elegans (clade V) and Acrobeloides nanus (clade IV). To examine A. nanus molecularly, we sequenced its genome and identified the expression profiles of all genes throughout embryogenesis. In comparison with C. elegans , A. nanus exhibits a much slower embryonic development and has a capacity for regulative compensation of missing early cells. We detected conserved stages between these species at the transcriptome level, as well as a prominent middevelopmental transition, at which point the two species converge in terms of their gene expression. Interestingly, we found that genes originating at the dawn of the Ecdysozoa supergroup show the least expression divergence between these two species. This led us to detect a correlation between the time of expression of a gene and its phylogenetic age: evolutionarily ancient and young genes are enriched for expression in early and late embryogenesis, respectively, whereas Ecdysozoa-specific genes are enriched for expression during the middevelopmental transition. Our results characterize the developmental constraints operating on each individual embryo in terms of developmental stages and genetic evolutionary history., Competing Interests: The authors declare no conflict of interest.

The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.

Gene duplication and alternative splicing are important mechanisms in the production of genomic novelties. Previous work has shown that a gene's family size and the number of splice variants it produces are inversely related, although the underlying reason is not well understood. Here, we report that gene length and expression level together explain this relationship. We found that gene lengths correlate with both gene duplication and alternative splicing: Longer genes are less likely to produce duplicates and more likely to exhibit alternative splicing. We show that gene length is a dynamic property, increasing with evolutionary time--due in part to the insertions of transposable elements--and decreasing following partial gene duplications. However, gene length alone does not account for the relationship between alternative splicing and gene duplication. A gene's expression level appears both to impose a strong constraint on its length and to restrict gene duplications. Furthermore, high gene expression promotes alternative splicing, in particular for long genes, and alternatively, short genes with low expression levels have large gene families. Our analysis of the human and mouse genomes shows that gene length and expression level are primary genic properties that together account for the relationship between gene duplication and alternative splicing and bias the origin of novelties in the genome., (© 2014 Grishkevich and Yanai; Published by Cold Spring Harbor Laboratory Press.)

Genomic analyses have shown that adjacent genes are often coexpressed. However, it remains unclear whether the observed coexpression is a result of functional organization or a consequence of adjacent active chromatin or transcriptional read-through, which may be free of selective biases. Here, we compare temporal expression profiles of one-to-one orthologs in conserved or divergent genomic positions in two genetically distant nematode species-Caenorhabditis elegans and C. briggsae-that share a near-identical developmental program. We find, for all major patterns of temporal expression, a substantive amount of gene expression divergence. However, this divergence is not random: Genes that function in essential developmental processes show less divergence than genes whose functions are not required for viability. Coexpression of gene neighbors in either species is highly divergent in the other, in particular when the neighborhood is not conserved. Interestingly, essential genes appear to maintain their expression profiles despite changes in neighborhoods suggesting exposure to stronger selection. Our results suggest that a significant fraction of the coexpression observed among gene neighbors may be accounted for by neutral processes, and further that these may be distinguished by comparative gene expression analyses.

Recent experiments revealed large-scale differences in the transcription programs of related species, yet little is known about the genetic basis underlying the evolution of gene expression and its contribution to phenotypic diversity. Here we describe a large-scale modulation of the yeast transcription program that is connected to the emergence of the capacity for rapid anaerobic growth. Genes coding for mitochondrial and cytoplasmic ribosomal proteins display a strongly correlated expression pattern in Candida albicans, but this correlation is lost in the fermentative yeast Saccharomyces cerevisiae. We provide evidence that this change in gene expression is connected to the loss of a specific cis-regulatory element from dozens of genes following the apparent whole-genome duplication event. Our results shed new light on the genetic mechanisms underlying the large-scale evolution of transcriptional networks.

Gene duplication and alternative splicing are distinct evolutionary mechanisms that provide the raw material for new biological functions. We explored their relationships in human and mouse and found an inverse correlation between the size of a gene's family and its use of alternatively spliced isoforms. A cross-organism analysis suggests that selection for genome-wide genic proliferation might be interchangeably met by either evolutionary mechanism.

We have systematically examined the domain composition across a comprehensive set of tissue-specific, midrange and housekeeping genes as defined by their mode of expression in 52 normal mouse tissues. We show a definite correlation between the number of domains and the degree of tissue specificity. This trend is further supported by a novel analysis involving the time of origin of each domain. Genes containing metazoan-specific domains are more prevalent in signal transduction and cell-communication pathways, and are depleted in primary metabolism. Our analyses suggest that highly modular gene products have been recruited for tissue-specific functions that are required in complex organisms.

Background: Gene fusions can be used as tools for functional prediction and also as evolutionary markers. Fused genes often show a scattered phyletic distribution, which suggests a role for processes other than vertical inheritance in their evolution., Results: The evolutionary history of gene fusions was studied by phylogenetic analysis of the domains in the fused proteins and the orthologous domains that form stand-alone proteins. Clustering of fusion components from phylogenetically distant species was construed as evidence of dissemination of the fused genes by horizontal transfer. Of the 51 examined gene fusions that are represented in at least two of the three primary kingdoms (Bacteria, Archaea and Eukaryota), 31 were most probably disseminated by cross-kingdom horizontal gene transfer, whereas 14 appeared to have evolved independently in different kingdoms and two were probably inherited from the common ancestor of modern life forms. On many occasions, the evolutionary scenario also involves one or more secondary fissions of the fusion gene. For approximately half of the fusions, stand-alone forms of the fusion components are encoded by juxtaposed genes, which are known or predicted to belong to the same operon in some of the prokaryotic genomes. This indicates that evolution of gene fusions often, if not always, involves an intermediate stage, during which the future fusion components exist as juxtaposed and co-regulated, but still distinct, genes within operons., Conclusion: These findings suggest a major role for horizontal transfer of gene fusions in the evolution of protein-domain architectures, but also indicate that independent fusions of the same pair of domains in distant species is not uncommon, which suggests positive selection for the multidomain architectures.

A universal property of microbial genomes is the considerable fraction of genes that are homologous to other genes within the same genome. The process by which these homologues are generated is not well understood, but sequence analysis of 20 microbial genomes unveils a recurrent distribution of gene family sizes. We show that a simple evolutionary model based on random gene duplication and point mutations fully accounts for these distributions and permits predictions for the number of gene families in genomes not yet complete. Our findings are consistent with the notion that a genome evolves from a set of precursor genes to a mature size by gene duplications and increasing modifications.