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Evolution of gene families: the multidrug resistance transporter genes in five related yeast species.

The available genomic sequences of five closely related hemiascomycetous yeast species (Kluyveromyces lactis, Kluyveromyces waltii, Candida glabrata, Ashbya (Eremothecium) gossypii with Saccharomyces cerevisiae as a reference) were analysed to identify multidrug resistance (MDR) transport proteins belonging to the ATP-binding cassette (ABC) and major facilitator superfamilies (MFS), respectively. The phylogenetic trees clearly demonstrate that a similar set of gene (sub)families already existed in the common ancestor of all five fungal species studied. However, striking differences exist between the two superfamilies with respect to the evolution of the various subfamilies. Within the ABC superfamily all six half-size transporters with six transmembrane-spanning domains (TMs) and most full-size transporters with 12 TMs have one and only one gene per genome. An exception is the PDR family, in which gene duplications and deletions have occurred independently in individual genomes. Among the MFS transporters, the DHA2 family (TC 2.A.1.3) is more variable between species than the DHA1 family (TC 2.A.1.2). Conserved gene order relationships allow to trace the evolution of most (sub)families, for which the Kluyveromyces lactis genome can serve as an optimal scaffold. Cross-species sequence alignment of orthologous upstream gene sequences led to the identification of conserved sequence motifs ("phylogenetic footprints"). Almost half of them match known sequence motifs for the MDR regulators described in S. cerevisiae. The biological significance of those and of the novel predicted motifs awaits to be confirmed experimentally.

ATP-Binding Cassette Transporters↗

Dosage, deletions and dominance: simple models of the evolution of gene expression.

Dominance of the wild-type allele over spontaneous null mutations, such as deletions, can be explained in terms of the effects of changes in enzyme dose on the flux of metabolic pathways. If ever increasing levels of enzyme activity have ever decreasing effects on the flux of the biochemical pathway, then halving of dosage will always have a lesser effect on flux than half the effect of complete removal of gene activity. Furthermore, if gene expression rates are high, then halving of dose can have a negligible effect on flux and dominance will be strong. Given that strong dominance appears to be common, this leaves open the issue of why enzyme activity levels are so high that a halving of expression rates is of minimal effect. Why produce so much surplus enzyme? One explanation, suggested by Haldane, is that selection favoured high expression levels as a defence against mutation. We model this scenario formally and show that protection from mutation is an extremely weak force determining expression levels. The selective coefficients are only of the order of the mutation rate. However, if we suppose a linear mapping of flux with fitness and a monotonic cost to increased gene expression, it follows simply that here exists an optimal level of gene expression. By contrast to the mutational model, doubling of gene expression rates when the system is distant from the optimum is associated with extremely high selective coefficients (orders of magnitude higher than the mutation rate). When the cost of gene expression is slight the optimal rate of expression is such that strong dominance will follow.

Animals↗

The Pem homeobox gene: rapid evolution of the homeodomain, X chromosomal localization, and expression in reproductive tissue.

A hallmark of homeobox genes is their high degree of sequence conservation in distantly related species. Here, we report the chromosomal localization, sequence, and expression pattern of an orphan homeobox gene, Pem, that encodes a homeodomain (HD) that has undergone a surprisingly high rate of evolutionary change. The N-terminal portion of the Pem HD, which includes the first two alpha-helices, exhibits only 44% sequence identity between rat Pem (r.Pem) and mouse Pem (m.Pem). This N-terminal subdomain exhibited an extremely high frequency of nonsynonymous substitutions, severalfold higher than other regions of the Pem protein. In contrast, the third helix, which is known to confer most of the base-specific contacts of HDs with DNA, was almost identical in r. Pem and m.Pem. Several lines of evidence suggested that the rat and mouse genes that we identified as Pem genes are true homologues: (1) the r.Pem and m.Pem genes both reside on the X chromosome; (2) they possess identical exon/intron splice junctions; (3) they both encode a distinctive motif upstream of the HD that is unique to Pem; and (4) the only m.Pem-like gene we were able to identify in the rat genome other than r.Pem was a pseudogene, r.Pem-ps, whose sequence and chromosomal localization indicated that it was derived by reverse transcription and reinsertion into the genome. The functional r.Pem gene is selectively expressed in placenta, testis, epididymis, and ovary. This expression pattern is of interest since other genes transcribed in reproductive tissue have also been shown to undergo high rates of sequence divergence. The high rate of amino acid substitutions in the N-terminal region of the Pem HD suggests the possibility of species-specific directional selection.

Alternative Splicing↗

Evolution of gene order conservation in prokaryotes.

BACKGROUND: As more complete genomes are sequenced, conservation of gene order between different organisms is emerging as an informative property of the genomes. Conservation of gene order has been used for predicting function and functional interactions of proteins, as well as for studying the evolutionary relationships between genomes. The reasons for the maintenance of gene order are still not well understood, as the organization of the prokaryote genome into operons and lateral gene transfer cannot possibly account for all the instances of conservation found. Comprehensive studies of gene order are one way of elucidating the nature of these maintaining forces. RESULTS: Gene order is extensively conserved between closely related species, but rapidly becomes less conserved among more distantly related organisms, probably in a cooperative fashion. This trend could be universal in prokaryotic genomes, as archaeal genomes are likely to behave similarly to bacterial genomes. Gene order conservation could therefore be used as a valid phylogenetic measure to study relationships between species. Even between very distant species, remnants of gene order conservation exist in the form of highly conserved clusters of genes. This suggests the existence of selective processes that maintain the organization of these regions. Because the clusters often span more than one operon, common regulation probably cannot be invoked as the cause of the maintenance of gene order. CONCLUSIONS: Gene order conservation is a genomic measure that can be useful for studying relationships between prokaryotes and the evolutionary forces shaping their genomes. Gene organization is extensively conserved in some genomic regions, and further studies are needed to elucidate the reason for this conservation.

Conserved Sequence↗

Epigenetic silencing may aid evolution by gene duplication.

Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function. However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones. Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence. We suggest that epigenetic silencing of duplicates might play this role in evolution. This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151-1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H. sapiens, M. musculus, and A. thaliana) than in organisms that do not have methylated genomes (S. cerevisiae, D. melanogaster, and C. elegans). We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly. We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner. This exposes each of the duplicates to negative selection, thus protecting from "pseudogenization." Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication-degeneration-complementation) process.

Animals↗

Two mouse early embryonic beta-globin gene sequences. Evolution of the nonadult beta-globins.

We have determined the complete nucleotide sequence of two early embryonic beta-globin genes of the BALB/c mouse: beta h0 and beta h1 X beta h1 codes for the embryonic z protein, while the beta h0 gene may be a minor early embryonic beta-globin gene. The general sequence organization of both genes is entirely analogous to other functional globin genes. There is, however, a 220-base pair insertion of unique sequence within the first intron of beta h0 X beta h0 and beta h1 are 96% homologous for 260 base pairs 5' to the AUG initiation codon, and 93% homologous throughout their coding regions. Analysis of the 5'-flanking sequence demonstrates that these genes are more nonadult-like than adult-like. The sequences show evidence for gene conversions among the mouse nonadult beta-globin genes that were limited to individual exons, presumably by the presence of non-homologous introns. We propose that this arrangement has the beneficial evolutionary effect of allowing gene conversion to act independently on regions of the protein with different structural or functional responsibilities. beta h0 and beta h1 are evolutionary homologs to the human fetal and rabbit beta 3 genes, while their manner of expression is similar to rabbit beta 3 and dissimilar to human fetal expression. The evolutionary history of the human beta-globin genes, therefore, includes the recruitment of an embryonic gene to fetal developmental control.

Animals↗

Broad-sense sexual selection, sex gene pool evolution, and speciation.

Studies of sexual selection have traditionally focused on explaining the extreme sexual dimorphism in male secondary sexual traits and elaborate mating behaviors displayed by males during courtship. In recent years, two aspects of sexual selection have received considerable attention in the literature: an extension of the sexual selection concept to other traits (i.e., postcopulatory behaviors, external and internal genital morphology, gametes, molecules), and alternative mechanistic explanations of the sexual selection process (i.e., coevolutionary runaway, good-genes, sexual conflicts). This article focuses on the need for an extension of sexual selection as a mechanism of change for courtship and (or) mating male characters (i.e., narrow-sense sexual selection) to all components of sexuality not necessarily related to courtship or mating (i.e., broad-sense sexual selection). We bring together evidence from a wide variety of organisms to show that sex-related genes evolve at a fast rate, and discuss the potential role of broad-sense sexual selection as an alternative to models that limit speciation to strict demographic conditions or treat it simply as an epiphenomenon of adaptive evolution.

Animals↗

Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family.

FK506-binding proteins (FKBPs) are peptidyl-prolyl cis/trans isomerases PPIases) that bind the immunosuppressive drug FK506. Of the many eukaryotic FKBPs that have been identified, FKBP65 is an endoplasmic reticulum-localized protein that associates with tropoelastin in the secretory pathway. Unlike any other FKBP characterized so far, FKBP65 is developmentally regulated and may be intimately involved in organogenesis. Here, we report the isolation, sequencing, and genomic organization of the mouse FKBP65 gene (Fkbp10) and provide a comparison with the human ortholog. Mouse Fkbp10 contains 10 exons and 9 introns encompassing 8.5 kb. The exon-intron organization of Fkbp10 displays a pattern of repetition that reflects the coding sequence of the four PPIase, or FK506-binding, domains present in the mature protein. The exon organization of the PPIase domains differs from that of the other FKBP family members. The evolution of the FKBP65 gene and other members of the FKBP multigene family were therefore investigated from a taxonomically diverse array of prokaryotic and eukaryotic taxa. These analyses suggest that the FKBP multigene family emerged early in the evolutionary history of eukaryotes, and during that time some members, including the FKBP65 gene, have experienced gene elongation by means of PPIase domain duplication.

Amino Acid Sequence↗

Transposable elements and the evolution of gene expression.

Most plant genomes are populated with enormous quantities of transposable elements (TEs) or sequences derived from TEs. The impact of TEs on their host has been addressed by characterizing mutations of the maize waxy and R genes caused by TE insertions. Association between a new class of TEs (called MITEs) and normal plant genes is also reviewed. The notion that different classes of TEs have found their respective niches in the maize genome is discussed.

DNA Transposable Elements↗

Characterization of the zebrafish tbx16 gene and evolution of the vertebrate T-box family.

We report on a new zebrafish T-box-containing gene, tbx16. It encodes a message that is first detected throughout the blastoderm soon after the initiation of zygotic gene expression. Following gastrulation, expression becomes restricted to paraxial mesoderm and later primarily to the developing tail bud. To gain an evolutionary prospective on the potential function of this gene, we have analyzed its phylogenetic relationships to known T-box genes from other species. Zebrafish tbx16 is likely orthologous to the chicken Tbx6L and Xenopus Xombi/Antipodean/Brat/VegT genes. Our analysis also shows that zebrafish tbx6 and mouse Tbx6 genes are paralogous to zebrafish tbx16. We present evidence which argues, that despite the same name and similar expression, zebrafish tbx6 and mouse Tbx6 genes are not orthologous to each other but instead represent relatively distant paralogs. The expression patterns of all genes are discussed in the light of their evolutionary relationships.

Amino Acid Sequence↗

Duplication and relocation of the functional DPY19L2 gene within low copy repeats.

BACKGROUND: Low copy repeats (LCRs) are thought to play an important role in recent gene evolution, especially when they facilitate gene duplications. Duplicate genes are fundamental to adaptive evolution, providing substrates for the development of new or shared gene functions. Moreover, silencing of duplicate genes can have an indirect effect on adaptive evolution by causing genomic relocation of functional genes. These changes are theorized to have been a major factor in speciation. RESULTS: Here we present a novel example showing functional gene relocation within a LCR. We characterize the genomic structure and gene content of eight related LCRs on human Chromosomes 7 and 12. Two members of a novel transmembrane gene family, DPY19L, were identified in these regions, along with six transcribed pseudogenes. One of these genes, DPY19L2, is found on Chromosome 12 and is not syntenic with its mouse orthologue. Instead, the human locus syntenic to mouse Dpy19l2 contains a pseudogene, DPY19L2P1. This indicates that the ancestral copy of this gene has been silenced, while the descendant copy has remained active. Thus, the functional copy of this gene has been relocated to a new genomic locus. We then describe the expansion and evolution of the DPY19L gene family from a single gene found in invertebrate animals. Ancient duplications have led to multiple homologues in different lineages, with three in fish, frogs and birds and four in mammals. CONCLUSION: Our results show that the DPY19L family has expanded throughout the vertebrate lineage and has undergone recent primate-specific evolution within LCRs.

Amino Acid Sequence↗

Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution.

The sequence of the entire RNA genome of the type flavivirus, yellow fever virus, has been obtained. Inspection of this sequence reveals a single long open reading frame of 10,233 nucleotides, which could encode a polypeptide of 3411 amino acids. The structural proteins are found within the amino-terminal 780 residues of this polyprotein; the remainder of the open reading frame consists of nonstructural viral polypeptides. This genome organization implies that mature viral proteins are produced by posttranslational cleavage of a polyprotein precursor and has implications for flavivirus RNA replication and for the evolutionary relation of this virus family to other RNA viruses.

Base Sequence↗

Rapid evolution of genes coding for variant surface glycoproteins in trypanosomes.

We have used cloned DNA complementary to the messenger RNAs (mRNAs) for different variant surface glycoproteins (VSGs) of Trypanosoma brucei, stock 427, to study the degree of conservation of the corresponding nuclear genes in related trypanosome stocks. Conservation of restriction endonuclease cleavage sites in and around these genes were assessed by hybridization of the complementary DNA (cDNA) probes to nuclear DNA blots of these stocks. One of the genes (117) was found essentially unaltered in 11 out of 12 stocks. A second gene (118) was absent in five stocks. In the seven stocks that contained it, four forms of this 118 gene could be distinguished that differ by loss/gain of several restriction sites. A third gene (221) was only present in T. brucei 427 and in none of 11 other stocks. We conclude that a sub-set of the genes for the variant antigens evolves at a very high rate and we favour the hypothesis that this is due to local hypermutagenesis.

Animals↗