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Molecular biology and evolution [journal]
- selscan: an efficient multi-threaded program to perform EHH-based scans for positive selection. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 10.
Haplotype-based scans to detect natural selection are useful to identify recent or ongoing positive selection in genomes. As both real and simulated genomic datasets grow larger, spanning thousands of samples and millions of markers, there is a need for a fast and efficient implementation of these scans for general use. Here we present selscan, an efficient multi-threaded application that implements Extended Haplotype Homozygosity (EHH), Integrated Haplotype Score (iHS), and Cross-population Extended Haplotype Homozygosity (XPEHH). selscan accepts phased genotypes in multiple formats, including TPED, and performs extremely well on both simulated and real data and over an order of magnitude faster than existing available implementations. It calculates iHS on chromosome 22 (22, 147 loci) across 204 CEU haplotypes in 353s on one thread (33s on 16 threads) and calculates XPEHH for the same data relative to 210 YRI haplotypes in 578s on one thread (52s on 16 threads). Source code and binaries (Windows, OSX and Linux) are available at https://github.com/szpiech/selscan.
- The Loss of Adipokine Genes in the Chicken Genome and Implications for Insulin Metabolism. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 10.
Gene loss is one of the main drivers in the evolution of genomes and species. The demonstration that a gene has been lost by pseudogenisation is truly complete when one finds the pseudogene in the orthologous genomic region with respect to active genes in other species. In some cases, the identification of such orthologous loci is not possible because of chromosomal rearrangements or if the gene of interest has not yet been sequenced. This question is particularly important in the case of birds because the genomes of avian species possess only about 15,000 predicted genes, in comparison with 20,000 in mammals. Yet, gene loss raises the question of which functions are affected by the changes in gene counts. We describe a systematic approach that makes it possible to demonstrate gene loss in the chicken genome even if a pseudogene has not been found. By using phylogenetic and synteny analysis in vertebrates, genome-wide comparisons between the chicken genome and ESTs, RNAseq data analysis, statistical analysis of the chicken genome, and Radiation Hybrid mapping, we show that resistin, TNFα and PAI-1 (SERPINE1), three genes encoding adipokines inhibiting insulin sensitivity, have been lost in chicken as well as zebra finch genomes. Moreover, omentin, a gene encoding an adipokine that enhances insulin sensitivity, has also been lost in the chicken genome. Overall, only one adipokine inhibiting insulin sensitivity, and five adipokines enhancing insulin sensitivity, are still present in the chicken genome. These genetic differences between mammals and chicken, given the functions of the genes in mammals, would have dramatic consequences on chicken endocrinology, leading to novel equilibriums especially in the regulation of energy metabolism, insulin sensitivity, as well as appetite and reproduction.
- Large-scale genetic survey provides insights into the captive management and reintroduction of giant pandas. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 10.
The captive genetic management of threatened species strives to preserve genetic diversity and avoid inbreeding to ensure populations remain available, healthy and viable for future reintroduction. Determining and responding to the genetic status of captive populations is therefore paramount to these programs. Here, we genotyped 19 microsatellite loci for 240 captive giant pandas (Ailuropoda melanoleuca) (~64% of the captive population) from four breeding centers, Wolong (WL), Chengdu (CD), Louguantai (LGT) and Beijing (BJ), and analyzed 655 base pairs of mitochondrial DNA control region sequence for 220 of these animals. High levels of genetic diversity and low levels of inbreeding were estimated in the breeding centers, indicating that the captive population is genetically healthy and deliberate further genetic input from wild animals is unnecessary. However, the LGT population faces a higher risk of inbreeding, and significant genetic structure was detected among breeding centers, with LGT-CD and WL-BJ clustering separately. Based on these findings, we highlight that: (i) the LGT population should be managed as an independent captive population to resemble the genetic distinctness of their Qinling Mountain origins; (ii) exchange between CD and WL should be encouraged because of similar wild founder sources; (iii) the selection of captive individuals for reintroduction should consider their geographic origin, genetic background and genetic contribution to wild populations; and (iv) combining our molecular genetic data with existing pedigree data will better guide giant panda breeding and further reduce inbreeding into the future.
- Evolution of Escherichia coli to 42°C and Subsequent Genetic Engineering Reveals Adaptive Mechanisms and Novel Mutations. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 10.
Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation to a desired environment. Here we performed ALE to 42°C of ten parallel populations of Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental conditions allowed selection based on exponential-phase growth rate, yielding strains that uniformly converged towards a similar phenotype along distinct genetic paths. Adapted strains possessed as few as 6 and as many as 55 mutations, and of the 144 genes that mutated in total, 14 arose independently across two or more strains. This mutational recurrence pointed to the key genetic targets underlying the evolved fitness increase. Genome engineering was used to introduce the novel ALE-acquired alleles in random combinations into the ancestral strain, and competition between these engineered strains reaffirmed the impact of the key mutations on the growth rate at 42°C. Interestingly, most of the identified key gene targets differed significantly from those found in similar temperature adaptation studies, highlighting the sensitivity of genetic evolution to experimental conditions and ancestral genotype. Additionally, transcriptomic analysis of the ancestral and evolved strains revealed a general trend for restoration of the global expression state back towards pre-heat stressed levels. This restorative effect was previously documented following evolution to metabolic perturbations, and thus may represent a general feature of ALE experiments. The widespread evolved expression shifts were enabled by a comparatively scant number of regulatory mutations, providing a net fitness benefit but causing suboptimal expression levels for certain genes, such as those governing flagellar formation, which then became targets for additional ameliorating mutations. Overall, the results of this study provide insight into the adaptation process and yield lessons important for the future implementation of ALE as a tool for scientific research and engineering.
- Cytonuclear evolution of rubisco in four allopolyploid lineages. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 10.
Allopolyploidization in plants entails the merger of two divergent nuclear genomes, typically with only one set (usually maternal) of parental plastidial and mitochondrial genomes and with an altered cytonuclear stoichiometry. Thus, we might expect cytonuclear coevolution to be an important dimension of allopolyploid evolution. Here we investigate cytonuclear coordination for the key chloroplast protein rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase), which is composed of nuclear-encoded, small subunits (SSUs) and plastid-encoded, large subunits (LSUs). By studying gene composition and diversity as well as gene expression in four model allopolyploid lineages, Arabidopsis, Arachis, Brassica, and Nicotiana, we demonstrate that paralogous nuclear-encoded rbcS genes within diploids are subject to homogenization via gene conversion, and that such concerted evolution via gene conversion characterizes duplicated genes (homoeologs) at the polyploid level. Many gene conversions in the polyploids are inter-genomic with respect to the diploid progenitor genomes, occur in functional domains of the homoeologous SSUs, and are directionally biased such that the maternal amino acid states are favored. This consistent preferential maternal-to-paternal gene conversion is mirrored at the transcriptional level, with a uniform transcriptional bias of the maternal-like rbcS homoeologs. These data, repeated among multiple diverse angiosperm genera for an important photosynthetic enzyme, suggest that cytonuclear coevolution may be mediated by inter-genomic gene conversion and altered transcription of duplicated, now homoeologous nuclear genes.
- Egg Yolk Protein Also Found to Play Key Role in Ant Socialization and Castes. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 3.
- Reduced representation genome sequencing suggests low diversity on the sex chromosomes of tonkean macaque monkeys. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 1.
In species with separate sexes, social systems can differ in the relative variances of male versus female reproductive success. Papion monkeys (macaques, mangabeys, mandrills, drills, baboons, geladas) exhibit hallmarks of a high variance in male reproductive success, including a female-biased adult sex ratio and prominent sexual dimorphism. To explore the potential genomic consequences of such sex differences, we used a reduced representation genome sequencing (RADseq) approach to quantifying polymorphism at sites on autosomes and sex chromosomes of the tonkean macaque (Macaca tonkeana), a species endemic to the Indonesian island of Sulawesi. The ratio of nucleotide diversity of the X chromosome to that of the autosomes was less than the value expected (0.75) with a 1:1 sex ratio and no sex differences in the variance in reproductive success. However, the significance of this difference was dependent on which outgroup was used to standardize diversity levels. Using a new model that includes the effects of varying population size, sex differences in mutation rate between the autosomes and X chromosome, and GC-biased gene conversion (gBGC) or selection on GC content, we found that the maximum likelihood estimate of the ratio of effective population size of the X chromosome to that of the autosomes was 0.68, which did not differ significantly from 0.75. We also found evidence for (a) a higher level of purifying selection on genic than non-genic regions, (b) gBGC or natural selection favoring increased GC content, (c) a dynamic demography characterized by population growth and contraction, (d) a higher mutation rate in males than females, and (e) a very low polymorphism level on the Y chromosome. These findings shed light on the population genomic consequences of sex differences in the variance in reproductive success, which appear to be modest in the tonkean macaque; they also suggest the occurrence of hitchhiking on the Y chromosome.
- Dependence of the sperm/oocyte decision on the Nucleosome Remodeling Factor Complex was acquired during recent C. briggsae evolution. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jul 1.
The major families of chromatin remodelers have been conserved throughout eukaryotic evolution. Because they play broad, pleiotropic roles in gene regulation, it was not known if their functions could change rapidly. Here we show that major alterations in the use of chromatin remodelers are possible, since the Nucleosome Remodeling Factor (NURF) Complex has acquired a unique role in the sperm/oocyte decision of the nematode C. briggsae. First, lowering the activity of C. briggsae NURF-1 or ISW-1, the core components of the NURF complex, causes germ cells to become oocytes rather than sperm. This observation is based on the analysis of weak alleles and null mutations that were induced with TALENs, and on RNA interference. Second, qRT-PCR data show that the C. briggsae NURF complex promotes the expression of Cbr-fog-1 and Cbr-fog-3, two genes that control the sperm/oocyte decision. This regulation occurs in the third larval stage, and affects the expression of later spermatogenesis genes. Third, double mutants reveal that the NURF complex and the transcription factor TRA-1 act independently on Cbr-fog-1 and Cbr-fog-3. TRA-1 binds both promoters and computer analyses predict that these binding sites are buried in nucleosomes, so we suggest that the NURF complex alters chromatin structure to allow TRA-1 access to Cbr-fog-1 and Cbr-fog-3. Finally, lowering NURF activity by mutation or RNA interference does not affect this trait in other nematodes, including the sister species C. nigoni, so it must have evolved recently. We conclude that altered chromatin remodeling could play an important role in evolutionary change.
- 350 million years of mitochondrial genome stasis in mosses, an early land plant lineage. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jun 30.
Among land plants, angiosperms have the structurally most labile mitochondrial genomes. By contrast, the so-called early land plants (e.g., mosses) seem to have completely static mitochondrial chromosomes. We assembled the complete mitochondrial genomes from 12 mosses spanning the moss tree of life, to assess a) the phylogenetic depth of the conserved mitochondrial gene content and order and b) the correlation between scattered sequence repeats and gene order lability in land plants. The mitochondrial genome of most mosses is approximately 100 kb in size, and thereby the smallest among land plants. Based on divergence time estimates, moss mitochondrial genome structure has remained virtually frozen for 350 million years, with only two independent gene losses and a single gene relocation detected across the macroevolutionary tree. This is the longest period of mitochondrial genome stasis demonstrated to date in a plant lineage. The complete lack of intergenic repeat sequences, considered to be essential for intragenomic recombinations, likely accounts for the evolutionary stability of moss mitochondrial genomes.
- The Coevolutionary Period of Wolbachia pipientis Infecting Drosophila ananassae and its Impact on the Evolution of the Host Germline Stem Cell Regulating Genes. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Jun 28.
The endosymbiotic bacteria Wolbachia pipientis is known to infect a wide range of arthropod species yet less is known about the coevolutionary history it has with its hosts. Evidence of highly identical W. pipientis strains in evolutionary divergent hosts suggests horizontal transfer between hosts. For example, Drosophila ananassae is infected with a W. pipientis strain that is nearly identical in sequence to a strain that infects both D. simulans and D. suzukii, suggesting recent horizontal transfer among these three species. However, it is unknown whether the W. pipientis strain had recently invaded all three species or a more complex infectious dynamic underlies the horizontal transfers. Here we have examined the coevolutionary history of D. ananassae and its resident W. pipientis to infer its period of infection. Phylogenetic analysis of D. ananassae mitochondrial DNA and W. pipientis DNA sequence diversity revealed the current W. pipientis infection is not recent. In addition, we examined the population genetics and molecular evolution of several Germline Stem Cell (GSC) regulating genes of D. ananassae. These studies reveal significant evidence of recent and long-term positive selection at stonewall in D. ananassae, while pumillio showed patterns of variation consistent with only recent positive selection. Previous studies had found evidence for adaptive evolution of two key germline differentiation genes, bag of marbles (bam) and benign gonial cell neoplasm (bgcn), in D. melanogaster and D. simulans and proposed that the adaptive evolution at these two genes was driven by arms race between the host GSC and W. pipientis. However, we did not find any statistical departures from a neutral model of evolution for bam and bgcn in D. ananassae despite our new evidence that this species has been infected with W. pipientis for a period longer than the most recent infection in D. melanogaster. In the end analyzing the GSC regulating genes individually showed two out of the seven genes to have evidence of selection. However, combining the dataset and fitting a specific population genetic model significant proportion of the nonsynonymous sites across the GSC regulating genes were driven to fixation by positive selection. Clearly the GSC system is under rapid evolution and potentially multiple drivers are causing the rapid evolution.