The evolutionary history of the SSX family of human C/T-antigens

C/T-antigens are endogenous proteins expressed in normal testis, ovary, and placenta, or in a variety of tumors. Such expression pattern makes the C/T antigens promising targets for cancer vaccines. The SSX family comprises several C/T antigens. Here we applied comparative genomics techniques to study the evolution of the SSX genes. The human genomic SSX locus includes 11 genes localized on the X chromosome in two separate regions 4 Mb apart. Recent pseudogenization of two SSX genes was demonstrated using the available expression data. A comparative analysis of the human, chimpanzee and mouse genomic loci allowed us to describe the phylogeny of the family and to reconstruct the evolutionary history of the locus in terms of elementary events.     

The eta-globin gene. Its long evolutionary history in the beta-globin gene family of mammals

In phylogenetic reconstructions by the parsimony method, utilizing 62 sequenced globin genes and pseudogenes (including 34 of the beta-globin gene family from eutherian orders Primates, Lagomorpha, Artiodactyla and Rodentia), the branch of primate psi beta pseudogenes and the goat embryonically expressed epsilon II gene group monophyletically together as orthologues of a common ancestral gene (labelled eta) distinct from orthologues of epsilon, gamma, delta and beta. This primate psi eta-goat eta branch is cladistically closer to epsilon and gamma than to delta and beta branches. In each eutherian order gene conversions replaced portions of delta by beta sequences, whereas in descent of Primates epsilon, gamma and eta mostly retained their separate ancient identities predating the radiation of Eutheria in all their exons and non-coding regions. The loci of the ancestral beta-globin gene cluster in basal eutherians and proto-primates, as deduced from beta-clusters representing the four eutherian orders, were linked 5'-epsilon-gamma-eta-delta-beta-3' with epsilon, gamma and eta being embryonically expressed genes, and delta and beta ontogenetically later expressed genes. Through deletions gamma was lost in artiodactyl evolution, eta in lagomorph and rodent evolution, and all DNA between exon 2 3' boundaries of eta and delta in prosimian lemuriform evolution (lemur having the hybrid pseudogene psi eta delta). Simian primates retained intact the five loci of the ancestral cluster. Not only did eta, after it became a pseudogene in the basal primates, persist intact in descent to present-day simians but in the line to hominoids it evolved during the last 40 million years at the decelerated rate of 1 X 10(-9) substitutions/site per year which is one-fifth the expected neutral rate. The possibility is suggested that the psi eta locus situated between fetal and adult chromosomal domains of the simian beta-globin gene cluster might play some role in a mechanism for ontogenetic switches of globin gene expression. However, not enough sequence data on genes and intergenic regions in DNA of species of primates and other mammals as yet exist to know if the slow rate of 1 X 10(-9) reflects the rate of a conserved functional gene or primarily reflects a decelerated neutral rate of hominoid DNA evolution, conceivably from enhanced DNA repair and longer generation times in hominoids. The further possibility is raised that gene correction (repair of damaged DNA that prevents emergence of new alleles) and gene conversion both more often involve strand copying of conserved than of rapidly evolving DNA.     

Nme protein family evolutionary history, a vertebrate perspective

Background  

The Nme family, previously known as Nm23 or NDPK, is involved in various molecular processes including tumor metastasis and some members of the family, but not all, exhibit a Nucleoside Diphosphate Kinase (NDPK) activity. Ten genes are known in humans, in which some members have been extensively studied. In non-mammalian species, the Nme protein family has received, in contrast, far less attention. The picture of the vertebrate Nme family remains thus incomplete and orthology relationships with mammalian counterparts were only partially characterized. The present study therefore aimed at characterizing the Nme gene repertoire in vertebrates with special interest for teleosts, and providing a comprehensive overview of the Nme gene family evolutionary history in vertebrates.     

Genomic clues of the evolutionary history of Bos indicus cattle

Together with their sister subspecies Bos taurus, zebu cattle (Bos indicus) have contributed to important socioeconomic changes that have shaped modern civilizations. Zebu cattle were domesticated in the Indus Valley 8000 years before present (YBP). From the domestication site, they expanded to Africa, East Asia, southwestern Asia and Europe between 4000 and 1300 YBP, intercrossing with B. taurus to form clinal variations of zebu ancestry across the landmass of Afro‐Eurasia. In the past 150 years, zebu cattle reached the Americas and Oceania, where they have contributed to the prosperity of emerging economies. The zebu genome is characterized by two mitochondrial haplogroups (I1 and I2), one Y chromosome haplogroup (Y3) and three major autosomal ancestral groups (Indian‐Pakistani, African and Chinese). Phenotypically, zebu animals are recognized by their hump, large ears and excess skin. They are rustic, resilient to parasites and capable of bearing the hot and humid climates of the tropics. Many resources are available to study the zebu genome, including commercial arrays of SNP, reference assemblies and publicly available genotypes and whole‐genome sequences. Nevertheless, many of these resources were initially developed to support research and subsidize industrial applications in B. taurus, and therefore they can produce bias in data analysis. The combination of genomics with precision agriculture holds great promise for the identification of genetic variants affecting economically important traits such as tick resistance and heat tolerance, which were naturally selected for millennia and played a major role in the evolution of B. indicus cattle.     

The evolutionary history of human and chimpanzee Y-chromosome gene loss

Recent studies have suggested that gene gain and loss may contribute significantly to the divergence between humans and chimpanzees. Initial comparisons of the human and chimpanzee Y-chromosomes indicate that chimpanzees have a disproportionate loss of Y-chromosome genes, which may have implications for the adaptive evolution of sex-specific as well as reproductive traits, especially because one of the genes lost in chimpanzees is critically involved in spermatogenesis in humans. Here we have characterized Y-chromosome sequences in gorilla, bonobo, and several chimpanzee subspecies for 7 chimpanzee gene-disruptive mutations. Our analyses show that 6 of these gene-disruptive mutations predate chimpanzee-bonobo divergence at approximately 1.8 MYA, which indicates significant Y-chromosome change in the chimpanzee lineage relatively early in the evolutionary divergence of humans and chimpanzees.     

Highly clustered zein gene sequences reveal evolutionary history of the multigene family

We have determined the nucleotide sequences of zein cDNA clones ZG14, ZG15, and ZG35. The three clones have 95 to 98% homology to the previously published sequence of clone A20, and 84% homology to sequences of the zein subfamily A30. Comparison of all sequences of the A30 and A20 subfamilies highlights the following features: the 5' nontranslated regions are 68 and 57 nucleotides in length for the A20- and A30-like mRNAs, respectively, and contain at least three repeats of the consensus sequence ACGAACAAta/gG; the majority of these genes are highly clustered as judged from pulsed-field gel electrophoresis of high molecular weight maize DNA. Furthermore, we discuss a model for the evolution of the multigene family which stresses the special importance of unequal crossingover and gene conversion in this system.     

The human protein disulfide isomerase gene family

Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs). These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX). As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR). Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.     

Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1) gene family

Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin.     

Immunoglobulin CH gene family in hominoids and its evolutionary history.

The organization of the human immunoglobulin CH gene suggests that a gene duplication involving the C gamma-C gamma-C epsilon-C alpha region has occurred during evolution. We previously showed that both chimpanzee and gorilla have two 5'-C epsilon-C alpha-3', as in human, and that orangutan, gibbon, and Old World monkeys have one C epsilon gene and one, two, and one C alpha gene(s), respectively. In addition to these clustered CH genes, there is one processed C epsilon pseudogene in each species. The present study revealed that orangutan and crab-eating macaque (an Old World monkey) both have one 5'-C epsilon-C alpha-3' and that gibbon has two 5'-C epsilon-C alpha-3', one C epsilon gene of which is completely deleted. By Southern analysis, the number of C gamma genes in all the nonhuman hominoids was estimated to be four to five, as in human, in comparison with two for crab-eating macaque. The C mu and C delta genes were estimated to be present as single copies in both hominoids and crab-eating macaque. Furthermore, it was proved that there are two copies of the C epsilon 5'-flanking region in both the orangutan and the gibbon genomes. These results show that gene duplication including the C gamma-C gamma-C epsilon-C alpha genes occurred in the common ancestor of hominoids and that subsequent deletion of the C epsilon gene (in orangutan, including one of the C alpha genes) occurred independently in each hominoid species.     

Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family

Background  

Chitinases (EC.3.2.1.14) hydrolyze the β-1,4-linkages in chitin, an abundant N-acetyl-β-D-glucosamine polysaccharide that is a structural component of protective biological matrices such as insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 (GH18) family of chitinases is an ancient gene family widely expressed in archea, prokaryotes and eukaryotes. Mammals are not known to synthesize chitin or metabolize it as a nutrient, yet the human genome encodes eight GH18 family members. Some GH18 proteins lack an essential catalytic glutamic acid and are likely to act as lectins rather than as enzymes. This study used comparative genomic analysis to address the evolutionary history of the GH18 multiprotein family, from early eukaryotes to mammals, in an effort to understand the forces that shaped the human genome content of chitinase related proteins.     

Plant resistome profiling in evolutionary old bog vegetation provides new clues to understand emergence of multi-resistance

The expanding antibiotic resistance crisis calls for a more in depth understanding of the importance of antimicrobial resistance genes (ARGs) in pristine environments. We, therefore, studied the microbiome associated with Sphagnum moss forming the main vegetation in undomesticated, evolutionary old bog ecosystems. In our complementary analysis of culture collections, metagenomic data and a fosmid library from different geographic sites in Europe, we identified a low abundant but highly diverse pool of resistance determinants, which targets an unexpectedly broad range of 29 antibiotics including natural and synthetic compounds. This derives both, from the extraordinarily high abundance of efflux pumps (up to 96%), and the unexpectedly versatile set of ARGs underlying all major resistance mechanisms. Multi-resistance was frequently observed among bacterial isolates, e.g. in Serratia, Rouxiella, Pandoraea, Paraburkholderia and Pseudomonas. In a search for novel ARGs, we identified the new class A β-lactamase Mm3. The native Sphagnum resistome comprising a highly diversified and partially novel set of ARGs contributes to the bog ecosystem´s plasticity. Our results reinforce the ecological link between natural and clinically relevant resistomes and thereby shed light onto this link from the aspect of pristine plants. Moreover, they underline that diverse resistomes are an intrinsic characteristic of plant-associated microbial communities, they naturally harbour many resistances including genes with potential clinical relevance.Subject terms: Environmental microbiology, Metagenomics, Microbial ecology     

The evolutionary history of human chromosome 7

We report on a comparative molecular cytogenetic and in silico study on evolutionary changes in human chromosome 7 homologs in all major primate lineages. The ancestral mammalian homologs comprise two chromosomes (7a and 7b/16p) and are conserved in carnivores. The subchromosomal organization of the ancestral primate segment 7a shared by a lemur and higher Old World monkeys is the result of a paracentric inversion. The ancestral higher primate chromosome form was then derived by a fission of 7b/16p, followed by a centric fusion of 7a/7b as observed in the orangutan. In hominoids two further inversions with four distinct breakpoints were described in detail: the pericentric inversion in the human/African ape ancestor and the paracentric inversion in the common ancestor of human and chimpanzee. FISH analysis employing BAC probes confined the 7p22.1 breakpoint of the pericentric inversion to 6.8 Mb on the human reference sequence map and the 7q22.1 breakpoint to 97.1 Mb. For the paracentric inversion the breakpoints were found in 7q11.23 between 76.1 and 76.3 Mb and in 7q22.1 at 101.9 Mb. All four breakpoints were flanked by large segmental duplications. Hybridization patterns of breakpoint-flanking BACs and the distribution of duplicons suggest their presence before the origin of both inversions. We propose a scenario by which segmental duplications may have been the cause rather than the result of these chromosome rearrangements.     

The evolutionary history of the amylase multigene family in Drosophila pseudoobscura

In Drosophila pseudoobscura, the amylase (Amy) multigene family is contained within a series of inversions, or gene arrangements, on the third chromosome. The Standard (ST), Santa Cruz (SC), and Tree Line (TL) inversions are central to the phylogeny of arrangements, and have clusters of other arrangements derived from them. The gene arrangements belonging to each of these three clusters have a characteristic number of Amy genes, ranging from three in ST to two in SC to one in TL. This distribution pattern can reflect a history of either duplications or deletions, although the data available in the past did not permit a decision between these alternatives. We provide unambiguous evidence that three Amy genes were present before the divergence of the ST, SC, and TL arrangements. Thus, the current status of the Amy multigene family is the result of deletions in the TL and SC arrangements, which created three new pseudogenes: TL Amy2-psi, TL Amy3-psi, and SC Amy3- psi. Analysis of pseudogene sequences revealed that, in the SC and ST arrangements, pseudogene evolution has been retarded, most likely due to the homogenization effect of gene conversion. Finally, by determining the original copy number, we have reconstructed the evolutionary history of the Amy multigene family and linked it with the evolution of the central gene arrangements.      

Early diversification and complex evolutionary history of the p53 tumor suppressor gene family

The p53 tumor suppressor plays the leading role in malignancy and in maintaining the genome's integrity and stability. p53 belongs to a gene family that in vertebrates includes two additional members, p63 and p73. Although similar in sequence, gene structure, and expression potential, the three p53 members differ in domain organization (in addition to the transactivation, DNA-binding, and tetramerization domains, p63 and p73 encode a sterile alpha motif, SAM, domain) and functional roles (with p63 and p73 assuming additional key roles in development). It is interesting to note that outside vertebrates, p53-like sequences have only been found as single genes, of either the p53 or the p63/p73 type (i.e., without or with a SAM domain, respectively). In this paper, we report that the diversification of this family is not restricted to the vertebrate lineage, as both a p53- and a p63/p73-type sequence are present in the unicellular choanoflagellate, Monosiga brevicollis. Furthermore, multiple independent duplication events involving p53-type sequences took place in several other animal lineages (cnidarians, flat worms, insects). These findings argue that selective factors other than those associated with the evolution of vertebrates are also relevant to the diversification of this family. Understanding the selective pressures associated with the multiple independent duplication events that took place in the p53 family and the roles of p53-like proteins outside vertebrates will provide further insight into the evolution of this very important family. In addition, the presence of both a p53 and a p63/73 copy in the unicellular M. brevicollis argues for its suitability as a model system for elucidating the functions of the p53 members and the mechanisms associated with their functional diversification.     

Molecular evolutionary analyses of the Arabidopsis L7 ribosomal protein gene family

Cytoplasmic ribosomal protein (r-protein) genes in Arabidopsis thaliana are encoded by 80 multigene families that contain between two and seven members. Gene family members are typically similar at the protein sequence level, with the most divergent members of any gene family retaining 94% identity, on average. However, three Arabidopsis r-protein families - S15a, L7 and P2 - contain highly divergent family members. Here, we investigated the organization, structure, expression and molecular evolution of the L7 r-protein family. Phylogenetic analyses showed that L7 r-protein gene family members constitute two distinct phylogenetic groups. The first group including RPL7B, RPL7C and RPL7D has homologs in plants, animals and fungi. The second group represented by RPL7A is found in plants but has no orthologs from other fully-sequenced eukaryotic genomes. These two groups may have derived from a duplication event prior to the divergence of animals and plants. All four L7 r-protein genes are expressed and all exhibit a differential expression in inflorescence and flowers. RPL7A and RPL7B are less expressed than the other genes in all tissues analyzed. Molecular characterization of nucleic and protein sequences of L7 r-protein genes and analysis of their codon usage did not indicate any functional divergence. The probable evolution of an extra-ribosomal function of group 2 genes is discussed.