Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Genetics and analysis of quantitative traits

I. the origin of species by means of natural selection

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

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Evolution of genes and genomes on the Drosophila phylogeny.

Next-generation sequencing technologies are revolutionizing human genomics, promising to yield draft genomes cheaply and quickly. One such technology has now been used to analyse much of the genetic code of a single individual — who happens to be James D. Watson. The procedure, which involves no cloning of the genomic DNA, makes use of the latest 454 parallel sequencing instrument. The sequence cost less than US$1 million (and a mere two months) to produce, compared to the approximately US$100 million reported for sequencing Craig Venter's genome by traditional methods. Still a major undertaking, but another step towards the goal of 'personalized genomes' and 'personalized medicine'. The DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels is reported. The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of ‘genomic medicine’. However, the formidable size of the diploid human genome1, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2–40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual2 by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of ‘personalized genome sequencing’.

/pdf/the-complete-genome-of-an-individual-by-massively-parallel-ayaq15s3pj.pdf

The complete genome of an individual by massively parallel DNA sequencing

Comparisons of chemosensory gene repertoires in human and non-human feeding Anopheles mosquitoes link olfactory genes to anthropophily

Abstract Genomic selection is a promising breeding technique for tree crops to accelerate the development of new cultivars. However, factors such as genetic structure can create spurious associations between genotype and phenotype due to the shared history between populations with different trait values. Genetic structure can therefore reduce the accuracy of the genotype to phenotype map, a fundamental requirement of genomic selection models. Here, we employed 272 single nucleotide polymorphisms from 208 Mangifera indica accessions to explore whether the genetic structure of the Australian mango gene pool explained variation in trunk circumference, fruit blush colour and intensity. Multiple population genetic analyses indicate the presence of four genetic clusters and show that the most genetically differentiated cluster contains accessions imported from Southeast Asia (mainly those from Thailand). We find that genetic structure was strongly associated with three traits: trunk circumference, fruit blush colour and intensity in M. indica . This suggests that the history of these accessions could drive spurious associations between loci and key mango phenotypes in the Australian mango gene pool. Incorporating such genetic structure in associations between genotype and phenotype can improve the accuracy of genomic selection, which can assist the future development of new cultivars. 

/pdf/the-influence-of-genetic-structure-on-phenotypic-diversity-30jdk1hr.pdf

The influence of genetic structure on phenotypic diversity in the Australian mango (Mangifera indica) gene pool

Storing and manipulating Next Generation Sequencing (NGS) file formats is an essential but difficult task in biological data analysis. The easyfm (easy file manipulation) toolkit (https://github.com/TaekAndBrendan/easyfm) makes manipulating commonly used NGS files more accessible to biologists. It enables them to perform end-to-end reproducible data analyses using a free standalone desktop application (available on Windows, Mac and Linux). Unlike existing tools (e.g. Galaxy), the Graphical User Interface (GUI)-based easyfm is not dependent on any high-performance computing (HPC) system and can be operated without an internet connection. This specific benefit allow easyfm to seamlessly integrate visual and interactive representations of NGS files, supporting a wider scope of bioinformatics applications in the life sciences. Author summary The analysis and manipulation of NGS data for understanding biological phenomena is an increasingly important aspect in the life sciences. Yet, most methods for analysing, storing and manipulating NGS data require complex command-line tools in HPC or web-based servers and have not yet been implemented in comprehensive, easy-to-use software. This is a major hurdle preventing more general application in the field of NGS data analysis and file manipulation. Here we present easyfm, a free standalone Graphical User Interface (GUI) software with Python support that can be used to facilitate the rapid discovery of target sequences (or user’s interest) in NGS datasets for novice users. For user-friendliness and convenience, easyfm was developed with four work modules and a secondary GUI window (herein secondary window), covering different aspects of NGS data analysis (mainly focusing on FASTA files), including post-processing, filtering, format conversion, generating results, real-time log, and help. In combination with the executable tools (BLAST+ and BLAT) and Python, easyfm allows the user to set analysis parameters, select/extract regions of interest, examine the input and output results, and convert to a wide range of file formats. To help augment the functionality of existing web-based and command-line tools, easyfm, a self-contained program, comes with extensive documentation (hosted at https://github.com/TaekAndBrendan/easyfm) including a comprehensive step-by-step guide.

/pdf/easyfm-an-easy-software-suite-for-file-manipulation-of-next-4cghjp3asi.pdf

easyfm: An easy software suite for file manipulation of Next Generation Sequencing data on desktops

Reinforcement occurs when natural selection strengthens behavioral discrimination to prevent costly interpopulation matings, such as when matings produce sterile hybrids. This evolutionary process can complete speciation, thereby providing a direct link between Darwin’s theory of natural selection and the origin of new species. My dissertation presents the first study on the genetics of reinforcement. This study is framed in a conceptual body that explains how genomic architecture, selection and recombination, interact to facilitate divergence in the presence of gene flow. In addition, in my dissertation I produced a dense recombination map for D. pseudoobscura, which together with the genome sequence opens many possibilities for classic population genetic and genomic analyses in this system. I examine a case of speciation by reinforcement in Drosophila. I present the first high-resolution genetic study of variation within species for female mating discrimination that is enhanced by natural selection. I show that reinforced mating discrimination is inherited as a dominant trait, exhibits variability within species, and may be influenced by a known set of candidate genes involved in olfaction. My results show that the genetics of reinforced mating discrimination is different from the genetics of mating discrimination between species, suggesting that overall mating discrimination might be a composite phenomenon, which in Drosophila could involve both auditory and olfactory cues. Examining the genetics of reinforcement provides a unique opportunity for both understanding the origin of new species in the face of gene flow and identifying the genetic basis of adaptive female species preferences, two major gaps in our understanding of speciation. 

Daniel Ortiz-Barrientos

Papers

Comparisons of chemosensory gene repertoires in human and non-human feeding Anopheles mosquitoes link olfactory genes to anthropophily

The influence of genetic structure on phenotypic diversity in the Australian mango (Mangifera indica) gene pool

easyfm: An easy software suite for file manipulation of Next Generation Sequencing data on desktops

The genetics of speciation by reinforcement