Biased gene conversion: implications for genome and sex evolution

Classical genetic studies show that gene conversion can favour some alleles over others. Molecular experiments suggest that gene conversion could favour GC over AT basepairs, leading to the concept of biased gene conversion towards GC (BGC(GC)). The expected consequence of such a process is the GC-enrichment of DNA sequences under gene conversion. Recent genomic work suggests that BGC(GC) affects the base composition of yeast, invertebrate and mammalian genomes. Hypotheses for the mechanisms and evolutionary origin of such a strange phenomenon have been proposed. Most BGC(GC) events probably occur during meiosis, which has implications for our understanding of the evolution of sex and recombination.     

Protein structure and neutral theory of evolution

The neutral theory of evolution is extended to the origin of protein molecules. Arguments are presented which suggest that the amino acid sequences of many globular proteins mainly represent "memorized" random sequences while biological evolution reduces to the "editing" these random sequences. Physical requirements for a functional globular protein are formulated and it is shown that many of these requirement do not involve strategical selection of amino acid sequences during biological evolution but are inherent also for typical random sequences. In particular, it is shown that random sequences of polar and amino acid residues can form alpha-helices and beta-strand with lengths and arrangement along the chain similar to those in real globular proteins. These alpha- and beta-regions in random sequences can form three-dimensional folding patterns also similar to those in proteins. The arguments are presented suggesting that even the tight packing of side groups inside protein core do not require very strong biological selection of amino acid sequences either. Thus many structural features of real proteins can exist also in random sequences and the biological selection is needed mainly for the creation of active site of protein and for their stability under physiological conditions.     

Induction of repetitive nucleotide sequences. The probable mechanisms of genome evolution and gene conversion

In the preselected site of pBR322 plasmid DNA related to the Tcr gene mutations were induced by the complementary single-stranded DNA restricts carrying alkylating groups. The alterations of the DNA primary structure in the mutagenized site were studied. It was found and that in the majority of mutants with the impaired Tcr gene function, the tandem direct repeats appeared. The repeats of 7-8 base pairs were localized in a fixed site of the Tcr gene, downstream of the palindrome. It is suggested that tandem repeats appear as a result of D-loops formation when single-stranded DNA forms a hairpin structure, due to the presence of palindromes. In the light of this notion, the tentative schemes of gene conversion and genome evolution are discussed.     

Molecular and cellular evidence for biased mitotic gene conversion in hybrid scallop

Background  

Concerted evolution has been believed to account for homogenization of genes within multigene families. However, the exact mechanisms involved in the homogenization have been under debate. Use of interspecific hybrid system allows detection of greater level of sequence variation, and therefore, provide advantage for tracing the sequence changes. In this work, we have used an interspecific hybrid system of scallop to study the sequence homogenization processes of rRNA genes.     

Transmembrane electron transport and the neutral theory of evolution

Based on the concept of "pairs of basic functional states" the evolution of the first chemiosmotic mechanism of energy conversion is discussed in terms of point mutations, gene duplications and of the neutral theory of evolution. A model for estimating the overall probability of the evolutionary step in question is presented, both for the "selectionist" and "neutralist" position. It is concluded that, concerning the present stage of knowledge, the evolution of transmembrane electron transport is an unsolved problem in evolutionary biology.     

Transmembrane electron transport and the neutral theory of evolution

Based on the concept of pairs of basic functional states the evolution of the first chemiosmotic mechanism of energy conversion is discussed in terms of point mutations, gene duplications and of the neutral theory of evolution. A model for estimating the overall probability of the evolutionary step in question is presented, both for the selectionist and neutralist position. It is concluded that, concerning the present stage of knowledge, the evolution of transmembrane electron transport is an unsolved problem in evolutionary biology.     

Horizontal gene transfer in microbial genome evolution

Horizontal gene transfer is the collective name for processes that permit the exchange of DNA among organisms of different species. Only recently has it been recognized as a significant contribution to inter-organismal gene exchange. Traditionally, it was thought that microorganisms evolved clonally, passing genes from mother to daughter cells with little or no exchange of DNA among diverse species. Studies of microbial genomes, however, have shown that genomes contain genes that are closely related to a number of different prokaryotes, sometimes to phylogenetically very distantly related ones. (Doolittle et al., 1990, J. Mol. Evol. 31, 383-388; Karlin et al., 1997, J. Bacteriol. 179, 3899-3913; Karlin et al., 1998, Annu. Rev. Genet. 32, 185-225; Lawrence and Ochman, 1998, Proc. Natl. Acad. Sci. USA 95, 9413-9417; Rivera et al., 1998, Proc. Natl. Acad. Sci. USA 95, 6239-6244; Campbell, 2000, Theor. Popul. Biol. 57 71-77; Doolittle, 2000, Sci. Am. 282, 90-95; Ochman and Jones, 2000, Embo. J. 19, 6637-6643; Boucher et al. 2001, Curr. Opin., Microbiol. 4, 285-289; Wang et al., 2001, Mol. Biol. Evol. 18, 792-800). Whereas prokaryotic and eukaryotic evolution was once reconstructed from a single 16S ribosomal RNA (rRNA) gene, the analysis of complete genomes is beginning to yield a different picture of microbial evolution, one that is wrought with the lateral movement of genes across vast phylogenetic distances. (Lane et al., 1988, Methods Enzymol. 167, 138-144; Lake and Rivera, 1996, Proc. Natl. Acad. Sci. USA 91, 2880-2881; Lake et al., 1999, Science 283, 2027-2028).     

Role of gene duplication in evolution

It is now known that many multigene and supergene families exist in eukaryote genomes: multigene families with uniform copy members like genes for ribosomal RNA, those with variable members like immunoglobulin genes, and supergene families such as those for various growth factor and hormone receptors. Many such examples indicate that gene duplication and subsequent differentiation are extremely important for organismal evolution. In particular, gene duplication could well have been the primary mechanism for the evolution of complexity in higher organisms. Population genetic models for the origin of gene families with diverse functions are presented, in which natural selection favors those genomes with more useful mutants in duplicated genes. Since any gene has a certain probability of degenerating by mutation, success versus failure in acquiring a new gene by duplication may be expressed as the ratio of probabilities of spreading of useful versus detrimental mutations in redundant gene copies. Also examined are the effects of gene duplication on evolution by compensatory advantageous mutations. Results of the analyses show that both natural selection and random drift are important for the origin of gene families. In addition, interaction between molecular mechanisms such as unequal crossing-over and gene conversion, and selection or drift is found to have a large effect on evolution by gene duplication.     

Both selective and neutral processes drive GC content evolution in the human genome

Background  

Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait.     

Detecting positive selection within genomes: the problem of biased gene conversion

The identification of loci influenced by positive selection is a major goal of evolutionary genetics. A popular approach is to perform scans of alignments on a genome-wide scale in order to find regions evolving at accelerated rates on a particular branch of a phylogenetic tree. However, positive selection is not the only process that can lead to accelerated evolution. Notably, GC-biased gene conversion (gBGC) is a recombination-associated process that results in the biased fixation of G and C nucleotides. This process can potentially generate bursts of nucleotide substitutions within hotspots of meiotic recombination. Here, we analyse the results of a scan for positive selection on genes on branches across the primate phylogeny. We show that genes identified as targets of positive selection have a significant tendency to exhibit the genomic signature of gBGC. Using a maximum-likelihood framework, we estimate that more than 20 per cent of cases of significantly elevated non-synonymous to synonymous substitution rates ratio (d_N/d_S), particularly in shorter branches, could be due to gBGC. We demonstrate that in some cases, gBGC can lead to very high d_N/d_S (more than 2). Our results indicate that gBGC significantly affects the evolution of coding sequences in primates, often leading to patterns of evolution that can be mistaken for positive selection.     

Horizontal gene transfer accelerates genome innovation and evolution

Horizontal gene transfer (HGT) spreads genetic diversity by moving genes across species boundaries. By rapidly introducing newly evolved genes into existing genomes, HGT circumvents the slow step of ab initio gene creation and accelerates genome innovation. However, HGT can only affect organisms that readily exchange genes (exchange communities). In order to define exchange communities and understand the internal and external environmental factors that regulate HGT, we analyzed approximately 20,000 genes contained in eight free-living prokaryotic genomes. These analyses indicate that HGT occurs among organisms that share similar factors. The most significant are genome size, genome G/C composition, carbon utilization, and oxygen tolerance.     

Poxvirus genome evolution by gene gain and loss

The poxviruses (Poxviridae) are a family of viruses with double-stranded DNA genomes and substantial numbers (often >200) of genes per genome. We studied the patterns of gene gain and loss over the evolutionary history of 17 poxvirus complete genomes. A phylogeny based on gene family presence/absence showed good agreement with families based on concatenated amino acid sequences of conserved single-copy genes. Gene duplications in poxviruses were often lineage specific, and the most extensively duplicated viral gene families were found in only a few of the genomes analyzed. A total of 34 gene families were found to include a member in at least one of the poxvirus genomes analyzed and at least one animal genome; in 16 (47%) of these families, there was evidence of recent horizontal gene transfer (HGT) from host to virus. Gene families with evidence of HGT included several involved in host immune defense mechanisms (the MHC class I, interleukin-10, interleukin-24, interleukin-18, the interferon gamma receptor, and tumor necrosis factor receptor II) and others (glutaredoxin and glutathione peroxidase) involved in resistance of cells to oxidative stress. Thus "capture" of host genes by HGT has been a recurrent feature of poxvirus evolution and has played an important role in adapting the virus to survive host antiviral defense mechanisms.     

Horizontal gene transfer, genome innovation and evolution

To what extent is the tree of life the best representation of the evolutionary history of microorganisms? Recent work has shown that, among sets of prokaryotic genomes in which most homologous genes show extremely low sequence divergence, gene content can vary enormously, implying that those genes that are variably present or absent are frequently horizontally transferred. Traditionally, successful horizontal gene transfer was assumed to provide a selective advantage to either the host or the gene itself, but could horizontally transferred genes be neutral or nearly neutral? We suggest that for many prokaryotes, the boundaries between species are fuzzy, and therefore the principles of population genetics must be broadened so that they can be applied to higher taxonomic categories.     

Horizontal gene transfer and gene conversion drive evolution of modular polyketide synthases

Soil bacteria live in a very competitive environment and produce many secondary metabolites; there appears to be strong selective pressure for evolution of new compounds. Secondary metabolites are the most important source of chemical structures for the pharmaceutical industry and an understanding of the evolutionary process should help in finding novel chemical entities. Modular polyketide synthases are a particularly interesting case for evolutionary studies, because much of the chemical structure can be predicted from DNA sequence. Previous evolutionary studies have concentrated on individual modules or domains and were not able to study the evolution of orthologues. This study overcame this problem by considering complete clusters as "organisms", so that orthologous modules and domains could be identified and used to characterise evolutionary pathways. Seventeen modular polyketide synthase clusters were identified that fell into six classes. Gene conversion within clusters was very common (affecting about 15?% of domains) and was detected by discordance in phylogenetic trees. An evolutionary model is proposed in which a single cross over between two different clusters (i.e. horizontal gene transfer) would generate a cluster of very different architecture with radically different chemical products; subsequent gene conversion and deletions would explore chemical variants. Two probable examples of such recombination were found. This model suggests strategies for detecting horizontal gene transfer in cluster evolution.