Relative contributions of structural designability and functional diversity in molecular evolution of duplicates

Analysis of increasingly saturated sequence databases have shown that gene family sizes are highly skewed with many families being small and few containing many, far-diverged homologs. Additionally, recently published results have identified a structural determinant of mutational plasticity: designability that correlates strongly with gene family size. In this paper, we explore the possible links between the two observations, exploring the possible effect of designability on duplication and divergence. We show that designability has an inverse of expected relationship with strength of selection. More designable domains that should have more mutational plasticity evolve slower. However, we also present evidence that recently duplicated genes have variable probability of locus fixation correlated with strength of selection. As expected, paralogs under stronger evolutionary pressure have a lower failure rate. Finally, we show that probability of pseudogene formation from gene duplication can be directly tied to designability and functional flexibility of the family. We present evidence that gene families with higher designability have diverged farther because of lower probability of pseudogenization. Additionally, mutational plasticity may play an integral role by influencing pseudogenization rate. Either way, we show that considering the failure rate of duplications is integral in understanding the determinants and dynamics of molecular evolution.     

Evolutionary rates for tuf genes in endosymbionts of aphids

The gene encoding elongation factor Tu (tuf) in aphid endosymbionts (genus Buchnera) evolves at rates of 1.3 x 10(-10) to 2.5 x 10(-10) nonsynonymous substitutions and 3.9 x 10(-9) to 8.0 x 10(-9) synonymous substitutions per position per year. These rates, which are at present among the most reliable substitution rates for protein-coding genes of bacteria, have been obtained by calibrating the nodes in the phylogenetic tree produced from the Buchnera EF-Tu sequences using divergence times for the corresponding ancestral aphid hosts. We also present data suggesting that the rates of nonsynonymous substitutions are significantly higher in the endosymbiont lineages than in the closely related free-living bacteria Escherichia coli and Salmonella typhimurium. Synonymous substitution rates for Buchnera approximate estimated mutation rates for E. coli and S. typhimurium, as expected if synonymous changes act as neutral mutations in Buchnera. We relate the observed differences in substitution frequencies to the absence of selective codon preferences in Buchnera and to the influence of Muller's ratchet on small asexual populations.      

Comparative analysis of FUR regulons in gamma-proteobacteria

Iron is an essential element for the survival and pathogenesis of bacteria. The strict control of iron homeostasis is mediated by the FUR repressor, which is highly conserved among various bacterial species. Here we apply the comparative genomics approach to analyze candidate Fur-binding sites in the genomes of Escherichia coli (K12 and O157:H7), Salmonella typhi, Yersinia pestis and Vibrio cholerae. We describe a number of new loci encoding siderophore biosynthesis and transport proteins. A new regulator of iron-acquisition systems was found in S.typhi. We predict FUR regulation for several virulence systems. We also predict FUR regulation for the chemotaxis system of V.cholerae that is probably involved in the process of pathogenesis.     

Purine regulon of gamma-proteobacteria: a detailed description

The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhi, Yersinia pestis, Haemophilus influenzae, Pasteurella multocida, Actinobacillus actinomycetemcomitans, and Vibrio cholerae. The palindromic binding site of the purine repressor (consensus ACGCAAACGTTTGCGT) is fairly well retained of genes encoding enzymes that participate in the synthesis of inosinemonophosphate from phosphoribozylpyrophosphate and in transfer of unicarbon groups, and also upstream of some transport protein genes. These genes may be regarded as the main part of the purine regulon. In terms of physiology, the regulation of the purC and gcvTHP/folD genes seems to be especially important, because the PurR site was found upstream of nonorthologous but functionally replaceable genes. However, the PurR site is poorly retained in front of orthologs of some genes belonging to the E. coli purine regulon, such as genes involved in general nitrogen metabolism, biosynthesis of pyrimidines, and synthesis of AMP and GMP from IMP, and also upstream of the purine repressor gene. It is predicted that purine regulons of the examined bacteria include the following genes: upp participating in synthesis of pyrimidines; uraA encoding an uracil transporter gene; serA involved in serine biosynthesis; folD responsible for the conversion of N5,N10-methenyl tetrahydrofolate into N10-formyltetrahydrofolate; rpiA involved in ribose metabolism; and protein genes with an unknown function (yhhQ and ydiK). The PurR site was shown to have different structure in different genomes. Thus, the tendency for a decline of the conservatism of site positions 2 and 15 was observed in genomes of bacteria belonging to the Pasteurellaceae and Vibrionaceae groups.     

Gene duplication, the evolution of novel gene functions, and detecting functional divergence of duplicates in silico

Duplication of genes increases the amount of genetic material on which evolution can work and has been considered of major importance for the development of biological novelties or to explain important transitions that have occurred during biological evolution. Recently, much research has been devoted to the study of the evolutionary and functional divergence of duplicated genes. Since the majority of genes are part of gene families, there is considerable interest in predicting differences in function between duplicates and assessing the functional redundancy of genes within gene families. In this review, we discuss the strengths and limitations of both older and novel approaches to investigate the evolution of duplicated genes in silico.     

Two tuf genes in the cyanobacterium Spirulina platensis.

Probes derived from the tufA gene of Escherichia coli have been utilized to detect homologous sequences on Spirulina platensis DNA. A 6-kilobase-pair fragment of S. platensis DNA appears to contain two sequences homologous to the E. coli gene. Thus, as reported for gram-negative bacteria, the cyanobacterium presumably contains two tuf genes.     

Insights into the molecular correlates modulating functional compensation between monogenic and polygenic disease gene duplicates in human

Functional redundancy by gene duplication appears to be a common phenomenon in biological system and hence understanding its underlying mechanism deserves much attention. Here, we investigated the differences between functional compensation of monogenic and polygenic disease genes which are unexplored till date. We found that the competence of functional buffering varies in the order of non-disease genes>monogenic disease genes>polygenic disease genes. This fact has been explained by the sequence identity, expression profile similarity, shared interaction partners and cellular locations between duplicated pairs. Moreover, we observed an inverse relationship between backup capacity and the non-synonymous substitution rate of disease and non-disease genes while the opposite trend is found for their corresponding paralogs. Logistic regression analysis among sequence identity, sharing of expression profile, interaction partners and cellular locations with backup capacity between duplicated pairs demonstrated that the sharing of expression profile is the most dominant regulator of backup capacity.     

Identification of duplicates for the optimization of carrot collection management

Molecular markers have proved their efficiency for the identification of duplicate accessions in genetic resources collections. Partners of the GENRES Carrot project decided to evaluate the use of molecular markers for the identification of carrot accession duplicates. As a model analysis, 21 presumed duplicate accessions of Jaune du Doubs were selected. Only accessions that were not distinguished on a morphological basis were subjected to molecular analysis. The crucial question was to determine the threshold required to declare whether accessions were duplicates or not. We used a strategy based on the comparison between intravarietal and intervarietal genetic distances. DNA extractions were made on 4–8 bulks of five individuals per accession, and the bulks were analysed using 75 AFLP markers. An additional set of 7 bulks was extracted from one accession to provide true control replicates. With the exception of the true duplicates, all the accessions were clearly differentiated. Based on these results, a general strategy for the identification of carrot duplicates is proposed.     

A diffusion model for the fate of tandem gene duplicates in diploids

Suppose one chromosome in one member of a population somehow acquires a duplicate copy of the gene, fully linked to the original gene's locus. Preservation is the event that eventually every chromosome in the population is a descendant of the one which initially carried the duplicate. For a haploid population in which the absence of all copies of the gene is lethal, the probability of preservation has recently been estimated via a diffusion approximation. That approximation is shown to carry over to the case of diploids and arbitrary strong selection against the absence of the gene. The techniques used lead to some new results. In the large population limit, it is shown that the relative probability that descendants of a small number of individuals carrying multiple copies of the gene fix in the population is proportional to the number of copies carried. The probability of preservation is approximated when chromosomes carrying two copies of the gene are subject to additional, fully non-functionalizing mutations, thereby modelling either an additional cost of replicating a longer genome, or a partial duplication of the gene. In the latter case the preservation probability depends only on the mutation rate to null for the duplicated portion of the gene.     

Mutational dynamics of murine angiogenin duplicates

Background  

Angiogenin (Ang) is a protein involved in angiogenesis by inducing the formation of blood vessels. The biomedical importance of this protein has come from findings linking mutations in Ang to cancer progression and neurodegenerative diseases. These findings highlight the evolutionary constrain on Ang amino acid sequence. However, previous studies comparing human Angiogenin with homologs from other phylogenetically related organisms have led to the conclusion that Ang presents a striking variability. Whether this variability has an adaptive value per se remains elusive. Understanding why many functional Ang paralogs have been preserved in mouse and rat and identifying functional divergence mutations at these copies may explain the relationship between mutations and function. In spite of the importance of testing this hypothesis from the evolutionarily and biomedical perspectives, this remains yet unaccomplished. Here we test the main mutational dynamics driving the evolution and function of Ang paralogs in mammals.     

The altered evolutionary trajectories of gene duplicates

Gene duplication is widely regarded as the predominant mechanism by which genes with new functions and associated phenotypic novelties arise. However, the mutational events and population-genetic mechanisms that lead to the short-term preservation of duplicate genes are not necessarily the same as those exhibited by well-established paralogs en route to the origin of new beneficial features. Thus, although recent genome-wide analyses have revealed striking patterns of protein-sequence divergence among the members of surviving paralogous gene families, the mechanisms responsible for the historical development of these patterns remain unclear.     

Retention of enzyme gene duplicates by subfunctionalization

Duplication-degeneration-complementation (DDC) describes a process by which evolving duplicates of a pleiotropic ancestral gene divide up the multiple functions of the ancestor between them (i.e. subfunctionalize), and this ultimately frustrates the rate of pseudogene formation. Focusing explicitly on enzyme-like pleiotropic function, we model DDC driven by sequence divergence between duplicates. The model incorporates an idealized sequence-function mapping in which enzyme-substrate binding affinity is related to hydrophobic versus polar (HP) amino-acid composition of tertiary structure about the binding pocket. In this sense, a transparent coupling between physical-chemical function of an enzyme and sequence evolution is presented.     

The fates of zebrafish Hox gene duplicates

In his 1970 book, Susumu Ohno stressed the importance of gene duplication in the evolution of the vertebrate genome and body plan. He elaborated the idea that duplication events provide novel genetic material on which evolution may act. Data are accumulating to show that extensive duplication events, perhaps incorporating the duplication of entire genomes, occurred in the lineage leading to teleost fishes. These duplications may have been pivotal in the explosive radiation of this highly successful vertebrate group. Thus, the teleosts provide us with an ideal opportunity to investigate the fates and functions of duplicated genes. A convenient system for these studies is the zebrafish, Danio rerio, which has become a popular genetic and embryological model.     

Models for loosely linked gene duplicates suggest lengthy persistence of both copies

Consider the appearance of a duplicate copy of a gene at a locus linked loosely, if at all, to the locus at which the gene is usually found. If all copies of the gene are subject to non-functionalizing mutations, then two fates are possible: loss of functional copies at the duplicate locus (loss of duplicate expression), or loss of functional copies at the original locus (map change). This paper proposes a simple model to address the probability of map change, the time taken for a map change and/or loss of duplicate expression, and considers where in the spectrum between loss of duplicate expression and map change such a duplicate complex is likely to be found. The findings are: the probability of map change is always half the reciprocal of the population size N, the time for a map change to occur is order NlogN generations, and that there is a marked tendency for duplicates to remain near equi-frequency with the gene at the original locus for a large portion of that time. This is in excellent agreement with simulations.     

Comparative analysis indicates regulatory neofunctionalization of yeast duplicates

Background  

Gene duplication provides raw material for the generation of new functions, but most duplicates are rapidly lost due to the initial redundancy in gene function. How gene function diversifies following duplication is largely unclear. Previous studies analyzed the diversification of duplicates by characterizing their coding sequence divergence. However, functional divergence can also be attributed to changes in regulatory properties, such as protein localization or expression, which require only minor changes in gene sequence.     

Artificial and natural duplicates in pyrosequencing reads of metagenomic data

Background  

Artificial duplicates from pyrosequencing reads may lead to incorrect interpretation of the abundance of species and genes in metagenomic studies. Duplicated reads were filtered out in many metagenomic projects. However, since the duplicated reads observed in a pyrosequencing run also include natural (non-artificial) duplicates, simply removing all duplicates may also cause underestimation of abundance associated with natural duplicates.