Genetics. 2013 May 11;

Authors: Kottler VA, Fadeev A, Weigel D, Dreyer C

Abstract
Males of the guppy (Poecilia reticulata) vary tremendously in their ornamental patterns, which are thought to have evolved in response to a complex interplay between natural and sexual selection. Although the selection pressures acting on the color patterns of the guppy have been extensively studied, little is known about the genes that control their ontogeny. Over 50 years ago, two autosomal color loci, blue and golden, have been described, which both play a decisive role in the formation of the guppy color pattern. Orange pigmentation is absent in the skin of guppies with a lesion in blue, suggesting a defect in xanthophore development. In golden mutants, the development of the melanophore pattern during embryogenesis and after birth is affected. Here, we show that blue and golden correspond to guppy orthologs of colony-stimulating factor 1 receptor a (csf1ra; previously called fms) and kita. Most excitingly, we found that both genes are required for the development of the black ornaments of guppy males, which in the case of csf1ra might be mediated by xanthophore-melanophore interactions. Furthermore, we provide evidence that two temporally and genetically distinct melanophore populations contribute to the adult camouflage pattern expressed in both sexes: one early-appearing and kita-dependent, and the other late-developing and kita-independent. The identification of csf1ra and kita mutants provides the first molecular insights into pigment pattern formation in this important model species for ecological and evolutionary genetics.

PMID: 23666934 [PubMed - as supplied by publisher]

Mol Biol Evol. 2013 May;30(5):1229-35

Authors: Hall BG

Abstract
Phylogenetic analysis is sometimes regarded as being an intimidating, complex process that requires expertise and years of experience. In fact, it is a fairly straightforward process that can be learned quickly and applied effectively. This Protocol describes the several steps required to produce a phylogenetic tree from molecular data for novices. In the example illustrated here, the program MEGA is used to implement all those steps, thereby eliminating the need to learn several programs, and to deal with multiple file formats from one step to another (Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 28:2731-2739). The first step, identification of a set of homologous sequences and downloading those sequences, is implemented by MEGA's own browser built on top of the Google Chrome toolkit. For the second step, alignment of those sequences, MEGA offers two different algorithms: ClustalW and MUSCLE. For the third step, construction of a phylogenetic tree from the aligned sequences, MEGA offers many different methods. Here we illustrate the maximum likelihood method, beginning with MEGA's Models feature, which permits selecting the most suitable substitution model. Finally, MEGA provides a powerful and flexible interface for the final step, actually drawing the tree for publication. Here a step-by-step protocol is presented in sufficient detail to allow a novice to start with a sequence of interest and to build a publication-quality tree illustrating the evolution of an appropriate set of homologs of that sequence. MEGA is available for use on PCs and Macs from www.megasoftware.net.

PMID: 23486614 [PubMed - in process]

Genetics. 2013 Apr;193(4):1197-208

Authors: Kousathanas A, Keightley PD

Abstract
Knowing the distribution of fitness effects (DFE) of new mutations is important for several topics in evolutionary genetics. Existing computational methods with which to infer the DFE based on DNA polymorphism data have frequently assumed that the DFE can be approximated by a unimodal distribution, such as a lognormal or a gamma distribution. However, if the true DFE departs substantially from the assumed distribution (e.g., if the DFE is multimodal), this could lead to misleading inferences about its properties. We conducted simulations to test the performance of parametric and nonparametric discretized distribution models to infer the properties of the DFE for cases in which the true DFE is unimodal, bimodal, or multimodal. We found that lognormal and gamma distribution models can perform poorly in recovering the properties of the distribution if the true DFE is bimodal or multimodal, whereas discretized distribution models perform better. If there is a sufficient amount of data, the discretized models can detect a multimodal DFE and can accurately infer the mean effect and the average fixation probability of a new deleterious mutation. We fitted several models for the DFE of amino acid-changing mutations using whole-genome polymorphism data from Drosophila melanogaster and the house mouse subspecies Mus musculus castaneus. A lognormal DFE best explains the data for D. melanogaster, whereas we find evidence for a bimodal DFE in M. m. castaneus.

PMID: 23341416 [PubMed - in process]

Genome Res. 2013 May;23(5):826-32

Authors: Kirkness EF, Grindberg RV, Yee-Greenbaum J, Marshall CR, Scherer SW, Lasken RS, Venter JC

Abstract
There is increasing evidence that the phenotypic effects of genomic sequence variants are best understood in terms of variant haplotypes rather than as isolated polymorphisms. Haplotype analysis is also critically important for uncovering population histories and for the study of evolutionary genetics. Although the sequencing of individual human genomes to reveal personal collections of sequence variants is now well established, there has been slower progress in the phasing of these variants into pairs of haplotypes along each pair of chromosomes. Here, we have developed a distinct approach to haplotyping that can yield chromosome-length haplotypes, including the vast majority of heterozygous single-nucleotide polymorphisms (SNPs) in an individual human genome. This approach exploits the haploid nature of sperm cells and employs a combination of genotyping and low-coverage sequencing on a short-read platform. In addition to generating chromosome-length haplotypes, the approach can directly identify recombination events (averaging 1.1 per chromosome) with a median resolution of <100 kb.

PMID: 23282328 [PubMed - in process]

Genetics. 2013 Feb;193(2):501-13

Authors: Andrés JA, Larson EL, Bogdanowicz SM, Harrison RG

Abstract
One of the central questions in evolutionary genetics is how much of the genome is involved in the early stages of divergence between populations, causing them to be reproductively isolated. In this article, we investigate genomic differentiation in a pair of closely related field crickets (Gryllus firmus and G. pennsylvanicus). These two species are the result of allopatric divergence and now interact along an extensive hybrid zone in eastern North America. Genes encoding seminal fluid proteins (SFPs) are often divergent between species, and it has been hypothesized that these proteins may play a key role in the origin and maintenance of reproductive isolation between diverging lineages. Hence, we chose to scan the accessory gland transcriptome to enable direct comparisons of differentiation for genes known to encode SFPs with differentiation in a much larger set of genes expressed in the same tissue. We have characterized differences in allele frequency between two populations for >6000 SNPs and >26,000 contigs. About 10% of all SNPs showed nearly fixed differences between the two species. Genes encoding SFPs did not have significantly elevated numbers of fixed SNPs per contig, nor did they seem to show larger differences than expected in their average allele frequencies. The distribution of allele frequency differences across the transcriptome is distinctly bimodal, but the relatively high proportion of fixed SNPs does not necessarily imply "ancient" divergence between these two lineages. Further studies of linkage disequilibrium and introgression across the hybrid zone are needed to direct our attention to those genome regions that are important for reproductive isolation.

PMID: 23172857 [PubMed - in process]

Genetics. 2012 Sep;192(1):33-53

Authors: Larracuente AM, Presgraves DC

Abstract
Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD(+) spermatids so that SD/SD(+) males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci--the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)--and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.

PMID: 22964836 [PubMed - indexed for MEDLINE]

Mol Biol Evol. 2012 Dec;29(12):3921-32

Authors: Gloria-Soria A, Moreno MA, Yund PO, Lakkis FG, Dellaporta SL, Buss LW

Abstract
We surveyed genetic variation in alr2, an allodeterminant of the colonial hydroid Hydractinia symbiolongicarpus. We generated cDNA from a sample of 239 Hydractinia colonies collected at Lighthouse Point, Connecticut, and identified 473 alr2 alleles, 198 of which were unique. Rarefaction analysis suggested that the sample was near saturation. Most alleles were rare, with 86% occurring at frequencies of 1% or less. Alleles were highly variable, diverging on average by 18% of the amino acids in a predicted extracellular domain of the molecule. Analysis of 152 full-length alleles confirmed the existence of two structural types, defined by exons 4-8 of the gene. Several residues of the predicted immunoglobulin superfamily-like domains display signatures of positive selection. We also identified 77 unique alr2 pseudogene sequences from 85 colonies. Twenty-seven of these sequences matched expressed alr2 sequences from other colonies. This observation is consistent with pseudogenes contributing to alr2 diversification through sequence donation. A more limited collection of animals was made from a distant, relict population of H. symbiolongicarpus. Sixty percent of the unique sequences identified in this sample were found to match sequences from the Lighthouse Point population. The large number of alr2 alleles, their degree of divergence, the predominance of rare alleles in the population, their persistence over broad spatial and temporal scales, and the signatures of positive selection in multiple residues of the putative recognition domain paint a consistent picture of negative-frequency-dependent selection operating in this system. The genetic diversity observed at alr2 is comparable to that of the most highly polymorphic genetic systems known to date.

PMID: 22855537 [PubMed - indexed for MEDLINE]

Proc Natl Acad Sci U S A. 2012 May 29;109(22):8629-34

Authors: Tian CF, Zhou YJ, Zhang YM, Li QQ, Zhang YZ, Li DF, Wang S, Wang J, Gilbert LB, Li YR, Chen WX

Abstract
The rhizobium-legume symbiosis has been widely studied as the model of mutualistic evolution and the essential component of sustainable agriculture. Extensive genetic and recent genomic studies have led to the hypothesis that many distinct strategies, regardless of rhizobial phylogeny, contributed to the varied rhizobium-legume symbiosis. We sequenced 26 genomes of Sinorhizobium and Bradyrhizobium nodulating soybean to test this hypothesis. The Bradyrhizobium core genome is disproportionally enriched in lipid and secondary metabolism, whereas several gene clusters known to be involved in osmoprotection and adaptation to alkaline pH are specific to the Sinorhizobium core genome. These features are consistent with biogeographic patterns of these bacteria. Surprisingly, no genes are specifically shared by these soybean microsymbionts compared with other legume microsymbionts. On the other hand, phyletic patterns of 561 known symbiosis genes of rhizobia reflected the species phylogeny of these soybean microsymbionts and other rhizobia. Similar analyses with 887 known functional genes or the whole pan genome of rhizobia revealed that only the phyletic distribution of functional genes was consistent with the species tree of rhizobia. Further evolutionary genetics revealed that recombination dominated the evolution of core genome. Taken together, our results suggested that faithfully vertical genes were rare compared with those with history of recombination including lateral gene transfer, although rhizobial adaptations to symbiotic interactions and other environmental conditions extensively recruited lineage-specific shell genes under direct or indirect control through the speciation process.

PMID: 22586130 [PubMed - indexed for MEDLINE]

Genetics. 2012 Jul;191(3):895-906

Authors: Peischl S, Kirkpatrick M

Abstract
Understanding adaptation in changing environments is an important topic in evolutionary genetics, especially in the light of climatic and environmental change. In this work, we study one of the most fundamental aspects of the genetics of adaptation in changing environments: the establishment of new beneficial mutations. We use the framework of time-dependent branching processes to derive simple approximations for the establishment probability of new mutations assuming that temporal changes in the offspring distribution are small. This approach allows us to generalize Haldane's classic result for the fixation probability in a constant environment to arbitrary patterns of temporal change in selection coefficients. Under weak selection, the only aspect of temporal variation that enters the probability of establishment is a weighted average of selection coefficients. These weights quantify how much earlier generations contribute to determining the establishment probability compared to later generations. We apply our results to several biologically interesting cases such as selection coefficients that change in consistent, periodic, and random ways and to changing population sizes. Comparison with exact results shows that the approximation is very accurate.

PMID: 22542964 [PubMed - indexed for MEDLINE]

Genome Res. 2012 Aug;22(8):1558-66

Authors: King EG, Merkes CM, McNeil CL, Hoofer SR, Sen S, Broman KW, Long AD, Macdonald SJ

Abstract
Genetic dissection of complex, polygenic trait variation is a key goal of medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, and an inability to identify variants that cumulatively explain the bulk of standing genetic variation in genome-wide association studies (GWAS). Thus, much of the heritability remains unexplained for most complex traits. Here we describe a novel, freely available resource for the Drosophila community consisting of two sets of recombinant inbred lines (RILs), each derived from an advanced generation cross between a different set of eight highly inbred, completely resequenced founders. The Drosophila Synthetic Population Resource (DSPR) has been designed to combine the high mapping resolution offered by multiple generations of recombination, with the high statistical power afforded by a linkage-based design. Here, we detail the properties of the mapping panel of >1600 genotyped RILs, and provide an empirical demonstration of the utility of the approach by genetically dissecting alcohol dehydrogenase (ADH) enzyme activity. We confirm that a large fraction of the variation in this classic quantitative trait is due to allelic variation at the Adh locus, and additionally identify several previously unknown modest-effect trans-acting QTL (quantitative trait loci). Using a unique property of multiparental linkage mapping designs, for each QTL we highlight a relatively small set of candidate causative variants for follow-up work. The DSPR represents an important step toward the ultimate goal of a complete understanding of the genetics of complex traits in the Drosophila model system.

PMID: 22496517 [PubMed - indexed for MEDLINE]

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2966-71

Authors: Huang R, Hippauf F, Rohrbeck D, Haustein M, Wenke K, Feike J, Sorrelle N, Piechulla B, Barkman TJ

Abstract
In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities.

PMID: 22315396 [PubMed - indexed for MEDLINE]

Genome Biol Evol. 2011;3:1039-52

Authors: Nevo E

Abstract
Environmental stress has played a major role in the evolution of living organisms (Hoffman AA, Parsons PA. 1991. Evolutionary genetics and environmental stress. Oxford: Oxford University Press; Parsons PA. 2005. Environments and evolution: interactions between stress, resource inadequacy, and energetic efficiency. Biol Rev Camb Philos Soc. 80:589-610). This is reflected by the massive and background extinctions in evolutionary time (Nevo E. 1995a. Evolution and extinction. Encyclopedia of Environmental Biology. New York: Academic Press, Inc. 1:717-745). The interaction between organism and environment is central in evolution. Extinction ensues when organisms fail to change and adapt to the constantly altering abiotic and biotic stressful environmental changes as documented in the fossil record. Extreme environmental stress causes extinction but also leads to evolutionary change and the origination of new species adapted to new environments. I will discuss a few of these global, regional, and local stresses based primarily on my own research programs. These examples will include the 1) global regional and local experiment of subterranean mammals; 2) regional experiment of fungal life in the Dead Sea; 3) evolution of wild cereals; 4) "Evolution Canyon"; 5) human brain evolution, and 6) global warming.

PMID: 21979157 [PubMed - indexed for MEDLINE]

Genetics. 2011 Dec;189(4):1427-37

Authors: Schneider A, Charlesworth B, Eyre-Walker A, Keightley PD

Abstract
The distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary genetics. Recently, methods have been developed for inferring the DFE that use information from the allele frequency distributions of putatively neutral and selected nucleotide polymorphic variants in a population sample. Here, we extend an existing maximum-likelihood method that estimates the DFE under the assumption that mutational effects are unconditionally deleterious, by including a fraction of positively selected mutations. We allow one or more classes of positive selection coefficients in the model and estimate both the fraction of mutations that are advantageous and the strength of selection acting on them. We show by simulations that the method is capable of recovering the parameters of the DFE under a range of conditions. We apply the method to two data sets on multiple protein-coding genes from African populations of Drosophila melanogaster. We use a probabilistic reconstruction of the ancestral states of the polymorphic sites to distinguish between derived and ancestral states at polymorphic nucleotide sites. In both data sets, we see a significant improvement in the fit when a category of positively selected amino acid mutations is included, but no further improvement if additional categories are added. We estimate that between 1% and 2% of new nonsynonymous mutations in D. melanogaster are positively selected, with a scaled selection coefficient representing the product of the effective population size, N(e), and the strength of selection on heterozygous carriers of ~2.5.

PMID: 21954160 [PubMed - indexed for MEDLINE]