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.     

The connexin gene family in mammals

Unannotated mammalian genome databases (dog, cow, opossum) were searched for candidate connexin genes, using sequences from annotated genomes (man, mouse). All 18 'multi-species' connexin genes, i.e., orthologs of connexin26 , 29/31.3 (duplicated in opossum), 30, 30.2/31.9, 30.3, 31, 31.1, 32, 36, 37, 39/40.1, 40, 43, 45, 44/46, 47, 50, and 57/62 , were found in dog, cow and opossum. Connexin25 and 58 have been considered specific for man, but evident orthologs of connexin25 were found in dog, cow and opossum, and orthologs of connexin58 were found in dog and cow. Moreover, a connexin43 -like sequence (approx. 80% identical to connexin43 ) was found in man, chimpanzee, dog and cow. In the three former species, the sequences were located on the X chromosome. In man, chimpanzee and cow, there were stop codons in all reading frames; these sequences are therefore judged as pseudogenes, called here Cx43pX . In the dog, the sequence contained an open reading frame for a protein of 35.7 kDa (connexin35.7). We suggest that these sequences are orthologs of connexin33 , previously considered as a rodent-specific connexin gene. Thus, connexin25 , 33 and 58 are not species-specific genes. However, the opossum may possess a candidate, connexin39.2 , without obvious orthologs in other mammals. Furthermore, pseudogenes of primate connexin31.3 and opossum connexin35 (one of the two orthologs of primate connexin31.3) were detected. These results suggest that the structure of the mammalian connexin gene family should be revised, especially with regard to the so-called 'species-specific' connexins .     

A molecular and evolutionary study of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata

Beta-globin gene families in eutherians (placental mammals) consist of a set of four or more developmentally regulated genes which are closely linked and, in general, arranged in the order 5'-embryonic/fetal genes- adult genes-3'. This cluster of genes is proposed to have arisen by tandem duplication of ancestral beta-globin genes, with the first duplication occurring 200 to 155 MYBP just prior to a period in mammalian evolution when eutherians and marsupials diverged from a common ancestor. In this paper we trace the evolutionary history of the beta-globin gene family back to the origins of these mammals by molecular characterization of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata. Using Southern and restriction analysis of total genomic DNA and bacteriophage clones of beta-like globin genes, we provide evidence that just two functional beta-like globin genes exist in this marsupial, including one embryonic- expressed gene (S.c-epsilon) and one adult-expressed gene (S.c-beta), linked in the order 5'-epsilon-beta-3'. The entire DNA sequence of the adult beta-globin gene is reported and shown to be orthologous to the adult beta-globin genes of the North American marsupial Didelphis virginiana and eutherian mammals. These results, together with results from a phylogenetic analysis of mammalian beta-like globin genes, confirm the hypothesis that a two-gene cluster, containing an embryonic- and an adult-expressed beta-like globin gene, existed in the most recent common ancester of marsupials and eutherians. Northern analysis of total RNA isolated from embryos and neonatals indicates that a switch from embryonic to adult gene expression occurs at the time of birth, coinciding with the transfer of the marsupial from a uterus to a pouch environment.      

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 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.     

The evolution of the type I interferon gene family in mammals

A phylogenetic analysis of mammalian type I interferon (IFN) genes showed: (1) that the three main subfamilies of these genes in mammals (IFN-, IFN-, and IFN-) diverged after the divergence of birds and mammals but before radiation of the eutherian orders and (2) that IFN- diverged first. Although apparent cases of interlocus recombination among mouse IFN- genes were identified, the hypothesis that coding regions of IFN- genes have been homogenized within species by interlocus recombination was not supported. Flanking regions as well as coding regions of IFN- were more similar within human and mouse than between these species; and reconstruction of the pattern of nucleotide substitution in IFN- coding regions of four mammalian species by the maximum parsimony method suggested that parallel substitutions have occurred far more frequently between species than within species. Therefore, it seems likely that IFN- genes have duplicated independently within different eutherian orders. In general, type I IFN genes are subject to purifying selection, which in the case of IFN- and IFN- is strongest in the putative receptor-binding domains. However, analysis of the pattern of nucleotide substitution among IFN- genes suggested that positive Darwinian selection may have acted in some cases to diversify members of this subfamily at the amino acid level.     

Retroposed elements as archives for the evolutionary history of placental mammals

Reconstruction of the placental mammalian (eutherian) evolutionary tree has undergone diverse revisions, and numerous aspects remain hotly debated. Initial hierarchical divisions based on morphology contained many misgroupings due to features that evolved independently by similar selection processes. Molecular analyses corrected many of these misgroupings and the superordinal hierarchy of placental mammals was recently assembled into four clades. However, long or rapid evolutionary periods, as well as directional mutation pressure, can produce molecular homoplasies, similar characteristics lacking common ancestors. Retroposed elements, by contrast, integrate randomly into genomes with negligible probabilities of the same element integrating independently into orthologous positions in different species. Thus, presence/absence analyses of these elements are a superior strategy for molecular systematics. By computationally scanning more than 160,000 chromosomal loci and judiciously selecting from only phylogenetically informative retroposons for experimental high-throughput PCR applications, we recovered 28 clear, independent monophyly markers that conclusively verify the earliest divergences in placental mammalian evolution. Using tests that take into account ancestral polymorphisms, multiple long interspersed elements and long terminal repeat element insertions provide highly significant evidence for the monophyletic clades Boreotheria (synonymous with Boreoeutheria), Supraprimates (synonymous with Euarchontoglires), and Laurasiatheria. More importantly, two retropositions provide new support for a prior scenario of early mammalian evolution that places the basal placental divergence between Xenarthra and Epitheria, the latter comprising all remaining placentals. Due to its virtually homoplasy-free nature, the analysis of retroposon presence/absence patterns avoids the pitfalls of other molecular methodologies and provides a rapid, unequivocal means for revealing the evolutionary history of organisms.     

The structure of the human beta-globin gene in beta-thalassaemia.

Twenty-one cases of beta 0 and beta +-thalassaemia have been analysed by restriction endonuclease mapping. In most cases no deletion in the regions surrounding the beta- and delta-globin genes could be detected. However, in a single Asian case of beta 0-thalassaemia, homozygous clinically, one of the homologous chromosomes contained a beta-globin gene with a deletion of 600 base pairs of DNA and comprising most or all of the 3' end of the structural gene including the EcoRI restriction site within the beta-globin coding sequence.     

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.     

Evolution of the interleukin-1 gene family in mammals

The phylogeny of interleukin-1 family genes shows that human interleukin-1 (IL-1) is more closely related to IL-1 of the bovine than to IL-1 of the mouse, whereas human interleukin-1 (IL-1) is more closely related to IL-1 of the mouse than to IL-1 of the bovine. The IL-1 receptor antagonist (IL-1) shows homology to the C-terminal region of both IL-1 and IL-1. In the C-terminal region, the IL-1 genes of human and mouse have diverged more from each other at nonsynonymous sites than have either IL-1 or IL-1; because the same pattern is not seen at synonymous sites, it must be due not to a difference in mutation rate but rather to a greater degree of functional constraint on this region in the IL-1 and IL-1 proteins than in the IL-1 protein. But synonymous sites in IL-1 of mouse have evolved more rapidly than in IL-1 of human, indicating a higher rate of mutation in the former gene. In the N-terminal region of the protein, nonsynonymous sites have evolved at similar rates in IL-1 and IL-1. The first exon of the IL-1 gene, which encodes the leader peptide, shows evidence of homology with the first exon of IL-1, which is not translated. Thus, it seems likely that IL-1 evolved by duplication of an IL-1 gene and loss of expression of exons 2–4. Correspondence to: A.L. Hughes     

Cabbage family affairs: the evolutionary history of Brassicaceae

Life without the mustard family (Brassicaceae) would be a world without many crop species and the model organism Arabidopsis (Arabidopsis thaliana) that has revolutionized our knowledge in almost every field of modern plant biology. Despite this importance, research breakthroughs in understanding family-wide evolutionary patterns and processes within this flowering plant family were not achieved until the past few years. In this review, we examine recent outcomes from diverse botanical disciplines (taxonomy, systematics, genomics, paleobotany and other fields) to synthesize for the first time a holistic view on the evolutionary history of the mustard family.     

Life history patterns in birds and mammals and their evolutionary interpretation

Summary It is argued that allometric principles account for most of the observed variation in the life history patterns amongst birds. To test this contention it is shown that traits such as incubation time, growth rates, age at first reproduction, lifespan, clutch weight and egg weight all scale to body weight with exponents similar to those found for analogous traits in mammals. It is then shown that most of the variation amongst bird taxa and between birds and mammals based on body weight allometry can be explained by variations in brain size, body temperature and metabolic rate, consistent with theories of growth and ageing derived from mammalian studies. Finally, it is suggested that the evidence for life histostory allometry is sufficiently strong that it argues for a more epigenetic view of life history patterns and their evolution than is generally conceded in most adaptation theories.     

Evolution of the interferon alpha gene family in eutherian mammals

Interferon alpha (IFNA) genes code for proteins with important signaling roles during the innate immune response. Phylogenetically, IFNA family members in eutherians (placental mammals) cluster together in a species-specific manner except for closely related species (i.e. Homo sapiens and Pan troglodytes) where gene-specific clustering is evident. Previous research has been unable to clarify whether gene conversion or recent gene duplication accounts for gene-specific clustering, partly because the similarity of members of the IFNA family within species has made it historically difficult to identify the exact composition of IFNA gene families. IFNA gene families were fully characterized in recently available genomes from Canis familiaris, Macaca mulatta, P. troglodytes and Rattus norvegicus, and combined with previously characterized IFNA gene families from H. sapiens and Mus musculus, for the analysis of both whole and partial gene conversion events using a variety of statistical methods. Gene conversion was inferred in every eutherian species analyzed and comparison of the IFNA gene family locus between primate species revealed independent gene duplication in M. mulatta. Thus, both gene conversion and gene duplication have shaped the evolution of the IFNA gene family in eutherian species. Scenarios may be envisaged whereby the increased production of a specific IFN-alpha protein would be beneficial against a particular pathogenic infection. Gene conversion, similar to duplication, provides a mechanism by which the protein product of a specific IFNA gene can be increased.