Horizontal gene transfer dynamics and distribution of fitness effects during microbial in silico evolution

<p>Abstract</p> <p>Background</p> <p>Horizontal gene transfer (HGT) is a process that facilitates the transfer of genetic material between organisms that are not directly related, and thus can affect both the rate of evolution and emergence of traits. Recent phylogenetic studies reveal HGT events are likely ubiquitous in the Tree of Life. However, our knowledge of HGT's role in evolution and biological organization is very limited, mainly due to the lack of ancestral evolutionary signatures and the difficulty to observe complex evolutionary dynamics in a laboratory setting. Here, we utilize a multi-scale microbial evolution model to comprehensively study the effect of HGT on the evolution of complex traits and organization of gene regulatory networks.</p> <p>Results</p> <p>Large-scale simulations reveal a distinct signature of the Distribution of Fitness Effect (DFE) for HGT events: during evolution, while mutation fitness effects become more negative and neutral, HGT events result in a balanced effect distribution. In either case, lethal events are significantly decreased during evolution (33.0% to 3.2%), a clear indication of mutational robustness. Interestingly, evolution was accelerated when populations were exposed to correlated environments of increasing complexity, especially in the presence of HGT, a phenomenon that warrants further investigation. High HGT rates were found to be disruptive, while the average transferred fragment size was linked to functional module size in the underlying biological network. Network analysis reveals that HGT results in larger regulatory networks, but with the same sparsity level as those evolved in its absence. Observed phenotypic variability and co-existing solutions were traced to individual gain/loss of function events, while subsequent re-wiring after fragment integration was necessary for complex traits to emerge.</p

Variable Mutation Rates as an Adaptive Strategy in Replicator Populations

For evolving populations of replicators, there is much evidence that the effect of mutations on fitness depends on the degree of adaptation to the selective pressures at play. In optimized populations, most mutations have deleterious effects, such that low mutation rates are favoured. In contrast to this, in populations thriving in changing environments a larger fraction of mutations have beneficial effects, providing the diversity necessary to adapt to new conditions. What is more, non-adapted populations occasionally benefit from an increase in the mutation rate. Therefore, there is no optimal universal value of the mutation rate and species attempt to adjust it to their momentary adaptive needs. In this work we have used stationary populations of RNA molecules evolving in silico to investigate the relationship between the degree of adaptation of an optimized population and the value of the mutation rate promoting maximal adaptation in a short time to a new selective pressure. Our results show that this value can significantly differ from the optimal value at mutation-selection equilibrium, being strongly influenced by the structure of the population when the adaptive process begins. In the short-term, highly optimized populations containing little variability respond better to environmental changes upon an increase of the mutation rate, whereas populations with a lower degree of optimization but higher variability benefit from reducing the mutation rate to adapt rapidly. These findings show a good agreement with the behaviour exhibited by actual organisms that replicate their genomes under broadly different mutation rates

Mutator dynamics in sexual and asexual experimental populations of yeast

<p>Abstract</p> <p>Background</p> <p>In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (<it>msh2</it>Δ) in sexual and asexual populations of <it>Saccharomyces cerevisiae</it>.</p> <p>Results</p> <p>Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually.</p> <p>Conclusions</p> <p>We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the <it>msh2Δ </it>mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that <it>msh2</it>Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.</p

Evolution of a New Function by Degenerative Mutation in Cephalochordate Steroid Receptors

Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models

Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populationsWe acknowledge the support by Uvigo Marine Research Centre funded by the “Excellence in Research (INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union through the ERDF Operational Programme Galicia 2014-2020. This work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a predoctoral (FPI) grant from Ministerio de Economía y Competitividad, SpainS