Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family.
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ABSTRACT:
SUBMITTER: Hanske J
PROVIDER: S-EPMC7042247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified. We have recently reported that the horse has also an extended CEA gene family. Since mechanisms of gene family expansion and diversification are not well understood we aimed to analyze the equine CEA gene family in detail. RESULTS:We found that the equine CEA gene family contains 17 functional CEACAM1-related genes. Nine of them were secreted molecules and eight CEACAMs contain transmembrane and cytoplasmic domain exons, the latter being in the focus of the present report. Only one (CEACAM41) gene has exons coding for activating signaling motifs all other CEACAM1 paralogs contain cytoplasmic exons similar to that of the inhibitory receptor CEACAM1. However, cloning of cDNAs showed that only one CEACAM1 paralog contain functional immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Three receptors have acquired a stop codon in the transmembrane domain and two have lost their inhibitory motifs due to alternative splicing events. In addition, alternative splicing eliminated the transmembrane exon sequence of the putative activating receptor, rendering it to a secreted molecule. Transfection of eukaryotic cells with FLAG-tagged alternatively spliced CEACAMs indicates that they can be expressed in vivo. Thus detection of CEACAM41 mRNA in activated PBMC suggests that CEACAM41 is secreted by lymphoid cells upon activation. CONCLUSIONS:The results of our study demonstrate that alternative splicing after gene duplication is a potent mechanism to accelerate functional diversification of the equine CEA gene family members. This potent mechanism has created novel CEACAM receptors with unique signaling capacities and secreted CEACAMs which potentially enables equine lymphoid cells to control distantly located immune cells.
| S-EPMC5856374 | biostudies-literature
Project description:Amphioxus Hairy genes have gone through a number of lineage-specific duplications, resulting in eight members, some of which are differentially expressed in the embryo. In order to gain insights into the evolution and function of this gene family we have compared their genomic structure and searched for conserved non-coding sequence elements. We have found that introns have been lost independently from these genes at least twice and after the duplication events. By carrying out phylogenetic footprinting between paralogues expressed in the embryo, we have found a differential distribution of conserved elements that could explain the limited overlap in expression patterns of Hairy genes in the amphioxus embryo. Furthermore, clustering of RBP-Jk binding sites in these conserved elements suggests that amphioxus Hairy genes are downstream targets of the Notch signaling pathway, as occurs in vertebrates. All of this evidence suggests that amphioxus Hairy genes have gone through a process of subfunctionalization shortly after their duplication, representing an extreme and rapid case of the duplication-degeneration-complementation model.
| S-EPMC1458425 | biostudies-literature
Project description:Very rapid rates of gene conversion were observed between duplicated alpha-amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly diverged and do not appear to be subject to gene conversion. Comparison of amylase sequences between the two species provides a clear demonstration that recurrent gene conversion does indeed lead to the concerted evolution of the gene pair.
| S-EPMC51074 | biostudies-other
Project description:Connecting protein sequence to function is becoming increasingly relevant since high-throughput sequencing studies accumulate large amounts of genomic data. In order to go beyond the existing database annotation, it is fundamental to understand the mechanisms underlying functional inheritance and divergence. If the homology relationship between proteins is known, can we determine whether the function diverged? In this work, we analyze different possibilities of protein sequence evolution after gene duplication and identify "inter-paralog inversions", i.e., sites where the relationship between the ancestry and the functional signal is decoupled. The amino acids in these sites are masked from being recognized by other prediction tools. Still, they play a role in functional divergence and could indicate a shift in protein function. We develop a method to specifically recognize inter-paralog amino acid inversions in a phylogeny and test it on real and simulated datasets. In a dataset built from the Epidermal Growth Factor Receptor (EGFR) sequences found in 88 fish species, we identify 19 amino acid sites that went through inversion after gene duplication, mostly located at the ligand-binding extracellular domain. Our work uncovers an outcome of protein duplications with direct implications in protein functional annotation and sequence evolution. The developed method is optimized to work with large protein datasets and can be readily included in a targeted protein analysis pipeline.
| S-EPMC9009777 | biostudies-literature
Project description:BACKGROUND: Gene duplications are a source of new genes and protein functions. The innovative role of duplication events makes families of paralogous genes an interesting target for studies in evolutionary biology. Here we study global trends in the evolution of human genes that resulted from recent duplications. RESULTS: The pressure of negative selection is weaker during a short time immediately after a duplication event. Roughly one fifth of genes in paralogous gene families are evolving asymmetrically: one of the proteins encoded by two closest paralogs accumulates amino acid substitutions significantly faster than its partner. This asymmetry cannot be explained by differences in gene expression levels. In asymmetric gene pairs the number of deleterious mutations is increased in one copy, while decreased in the other copy as compared to genes constituting non-asymmetrically evolving pairs. The asymmetry in the rate of synonymous substitutions is much weaker and not significant. CONCLUSIONS: The increase of negative selection pressure over time after a duplication event seems to be a major trend in the evolution of human paralogous gene families. The observed asymmetry in the evolution of paralogous genes shows that in many cases one of two gene copies remains practically unchanged, while the other accumulates functional mutations. This supports the hypothesis that slowly evolving gene copies preserve their original functions, while fast evolving copies obtain new specificities or functions.
| S-EPMC2942815 | biostudies-literature
Project description:BackgroundIt has been proposed that recently duplicated genes are more likely to be redundant with one another compared to ancient paralogues. The evolutionary logic underpinning this idea is simple, as the assumption is that recently derived paralogous genes are more similar in sequence compared to members of ancient gene families. We set out to test this idea by using molecular phylogenetics and exploiting the genetic tractability of the model nematode, Caenorhabditis elegans, in studying the nematode-specific family of Hedgehog-related genes, the Warthogs. Hedgehog is one of a handful of signal transduction pathways that underpins the development of bilaterian animals. While having lost a bona fide Hedgehog gene, most nematodes have evolved an expanded repertoire of Hedgehog-related genes, ten of which reside within the Warthog family.ResultsWe have characterised their evolutionary origin and their roles in C. elegans and found that these genes have adopted new functions in aspects of post-embryonic development, including left-right asymmetry and cell fate determination, akin to the functions of their vertebrate counterparts. Analysis of various double and triple mutants of the Warthog family reveals that more recently derived paralogues are not redundant with one another, while a pair of divergent Warthogs do display redundancy with respect to their function in cuticle biosynthesis.ConclusionsWe have shown that newer members of taxon-restricted gene families are not always functionally redundant despite their recent inception, whereas much older paralogues can be, which is considered paradoxical according to the current framework in gene evolution.
| S-EPMC7919330 | biostudies-literature
Project description:BackgroundMany population genetic and phylogenetic analyses of mitochondrial DNA (mtDNA) assume that mitochondrial genomes do not undergo recombination. Recently, concerted evolution of duplicated mitochondrial control regions has been documented in a range of taxa. Although the molecular mechanism that facilitates concerted evolution is unknown, all proposed mechanisms involve mtDNA recombination.ResultsHere, we document a duplication of a large region (cytochrome b, tRNAThr, tRNAPro, ND6, tRNAGlu and the control region) in the mitochondrial genome of three related seabird species. To investigate the evolution of duplicate control regions, we sequenced both control region copies (CR1 and CR2) from 21 brown (Sula leucogaster), 21 red-footed (S. sula) and 21 blue-footed boobies (S. nebouxii). Phylogenetic analysis suggested that the duplicated control regions are predominantly evolving in concert; however, approximately 51 base pairs at the 5' end of CR1 and CR2 exhibited a discordant phylogenetic signal and appeared to be evolving independently.ConclusionsBoth the structure of the duplicated region and the conflicting phylogenetic signals are remarkably similar to a pattern found in Thalassarche albatrosses, which are united with boobies in a large clade that includes all procellariiform and most pelecaniform seabirds. Therefore we suggest that concerted evolution of duplicated control regions either is taxonomically widespread within seabirds, or that it has evolved many times.
| S-EPMC2820450 | biostudies-literature
Project description:The pregnancy-associated glycoproteins (PAG) are putative peptide-binding proteins and products of a large family of genes whose expression is localized to the placental surface epithelium of artiodactyl species. We have tested the hypothesis that natural selection has favored diversification of these genes by examining patterns of nucleotide substitution in a sample of 28 closely related bovine, caprine, and ovine family members that are expressed only in trophoblast binucleate cells. Three observations were made. First, in codons encoding highly variable domains of the proteins, there was a greater accumulation of both synonymous and nonsynonymous mutations than in the more conserved regions of the genes. Second, in the variable regions, the mean number of nonsynonymous nucleotide substitutions per site was significantly greater than the mean number of synonymous substitutions per site. Third, nonsynonymous changes affecting amino acid charge occurred more frequently than expected under random substitution. This unusual pattern of nucleotide substitution implies that natural selection has acted to diversify these PAG molecules at the amino acid level, which in turn suggests that these molecules have undergone functional diversification. We estimate that the binucleate cell-expressed PAG originated 52 +/- 6 million years ago, soon after the divergence of the ruminant lineage. Thus, rapid functional diversification of PAG expressed in trophoblast binucleate cells seems to have been associated with the origin of this unique placental adaptation.
| S-EPMC16237 | biostudies-literature
Project description:The relationship between animal mating system variation and patterns of protein polymorphism and divergence is poorly understood. Drosophila provides an excellent system for addressing this issue, as there is abundant interspecific mating system variation. For example, compared to D. melanogaster subgroup species, repleta group species have higher remating rates, delayed sexual maturity, and several other interesting differences. We previously showed that accessory gland protein genes (Acp's) of Drosophila mojavensis and D. arizonae evolve more rapidly than Acp's in the D. melanogaster subgroup and that adaptive Acp protein evolution is likely more common in D. mojavensis/D. arizonae than in D. melanogaster/D. simulans. These findings are consistent with the idea that greater postcopulatory selection results in more adaptive evolution of seminal fluid proteins in the repleta group flies. Here we report another interesting evolutionary difference between the repleta group and the D. melanogaster subgroup Acp's. Acp gene duplications are present in D. melanogaster, but their high sequence divergence indicates that the fixation rate of duplicated Acp's has been low in this lineage. Here we report that D. mojavensis and D. arizonae genomes contain several very young duplicated Acp's and that these Acp's have experienced very rapid, adaptive protein divergence. We propose that rapid remating of female desert Drosophila generates selection for continuous diversification of the male Acp complement to improve male fertilization potential. Thus, mating system variation may be associated with adaptive protein divergence as well as with duplication of Acp's in Drosophila.
| S-EPMC2034610 | biostudies-literature
Project description:Vertebrates possess 2 proteins with vitamin K oxidoreductase (VKOR) activity: VKORC1, whose vitamin K reduction supports vitamin K-dependent (VKD) protein carboxylation, and VKORC1-like 1 (VKORC1L1), whose function is unknown. VKD proteins include liver-derived coagulation factors, and hemorrhaging and lethality were previously observed in mice lacking either VKORC1 or the γ-glutamyl carboxylase (GGCX) that modifies VKD proteins. Vkorc1-/- mice survived longer (1 week) than Ggcx-/- mice (midembryogenesis or birth), and we assessed whether VKORC1L1 could account for this difference. We found that Vkorc1-/-;Vkorc1l1-/- mice died at birth with severe hemorrhaging, indicating that VKORC1L1 supports carboxylation during the pre- and perinatal periods. Additional studies showed that only VKORC1 sustains hemostasis beyond P7. VKORC1 expression and VKOR activity increased during late embryogenesis and following birth, while VKORC1L1 expression was unchanged. At P0, most (>99%) VKOR activity was due to VKORC1. Prothrombin mRNA, protein, and carboxylation also increased during this period, as did mRNA levels of coagulation factors encoding genes F7, F9, and F10. VKORC1L1 levels in Vkorc1-/- mouse liver may therefore be insufficient for supporting carboxylation beyond day 7. In support of this conclusion, VKORC1L1 overexpression in liver rescued carboxylation and hemostasis in adult Vkorc1-/- mice. These findings establish that VKORC1L1 supports VKD protein carboxylation in vivo.
| S-EPMC5821188 | biostudies-literature