Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build- up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation

Composite likelihood estimation of demographic parameters

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Most existing likelihood-based methods for fitting historical demographic models to DNA sequence polymorphism data to do not scale feasibly up to the level of whole-genome data sets. Computational economies can be achieved by incorporating two forms of pseudo-likelihood: composite and approximate likelihood methods. Composite likelihood enables scaling up to large data sets because it takes the product of marginal likelihoods as an estimator of the likelihood of the complete data set. This approach is especially useful when a large number of genomic regions constitutes the data set. Additionally, approximate likelihood methods can reduce the dimensionality of the data by summarizing the information in the original data by either a sufficient statistic, or a set of statistics. Both composite and approximate likelihood methods hold promise for analyzing large data sets or for use in situations where the underlying demographic model is complex and has many parameters. This paper considers a simple demographic model of allopatric divergence between two populations, in which one of the population is hypothesized to have experienced a founder event, or population bottleneck. A large resequencing data set from human populations is summarized by the joint frequency spectrum, which is a matrix of the genomic frequency spectrum of derived base frequencies in two populations. A Bayesia

High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch ()

Background Two subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system. Results Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies. Conclusions Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences

Methods for estimating demography and detecting between-locus differences in the effective population size and mutation rate

It is known that the effective population size (Ne) and the mutation rate (u) vary across the genome. Here we show that ignoring this heterogeneity may lead to biased estimates of past demography. To solve the problem, we develop new methods for jointly inferring past changes in population size and detecting variation in Ne and u between loci. These methods rely on either polymorphism data alone or both polymorphism and divergence data. In addition to inferring demography, we can use the methods to study a variety of questions: (1) comparing sex chromosomes to autosomes (for finding evidence for male-driven evolution, an unequal sex ratio, or sex-biased demographic changes); (2) analysing multi-locus data from within autosomes or sex chromosomes (for studying determinants of variability in Ne and u). Simulations suggest that the methods can provide accurate parameter estimates and have substantial statistical power for detecting difference in Ne and u. As an example, we use the methods to analyse a polymorphism dataset from Drosophila simulans. We find clear evidence for rapid population expansion. The results also indicate that the autosomes have a higher mutation rate than the X chromosome, and that the sex ratio is probably female-biased. The new methods have been implemented in a user-friendly package

Efficient Test Case Generation for AUTOSAR Basic Software Code Generators

In the contemporary automotive industry, the complexity of software architectures for electronic control units (ECUs) has increased drastically. Aiming to improve the complexity management of these architectures, a worldwide partnership of car manufacturers and suppliers has created a standardized approach called AUTOSAR (AUTomotive Open System ARchitecture) (AUTOSAR Basics, 2012). At the highest abstraction level, the architecture of AUTOSAR contains three software layers which run on a Microcontroller. These three layers are Application Layer, Runtime Environment (RTE) and Basic Software (BSW) (AUTOSAR Layered software architecture, 2011). The BSW layer is further divided into multiple software modules which provide basic services such as memory management and bus communication (Mecel, 2013). These software modules can be configured to satisfy the needs of the customer. Testing these configurations requires a large amount of effort and time, especially since they are manually generated. This thesis deals with the automatic generation of these test cases, the configurations of the BSW modules. Two test case generation approaches were developed and compared. The first is random generation where elements to be added to the test case are chosen in a random manner. The second is pairwise generation where elements are added to the test case based on satisfying all pairs of element values. The experiments conducted to compare the two generation techniques ran the configurations created for three BSW modules through their SCGs (Source Code Generators) and showed that both techniques have the ability to uncover problems within a SCG. This thesis was conducted as a case study at Mecel AB in Gothenburg

POPBAM: Tools for Evolutionary Analysis of Short Read Sequence Alignments

Background While many bioinformatics tools currently exist for assembling and discovering variants from next-generation sequence data, there are very few tools available for performing evolutionary analyses from these data. Evolutionary and population genomics studies hold great promise for providing valuable insights into natural selection, the effect of mutations on phenotypes, and the origin of species. Thus, there is a need for an extensible and flexible computational tool that can function into a growing number of evolutionary bioinformatics pipelines. Results This paper describes the POPBAM software, which is a comprehensive set of computational tools for evolutionary analysis of whole-genome alignments consisting of multiple individuals, from multiple populations or species. POPBAM works directly from BAM-formatted assembly files, calls variant sites, and calculates a variety of commonly used evolutionary sequence statistics. POPBAM is designed primarily to perform analyses in sliding windows across chromosomes or scaffolds. POPBAM accurately measures nucleotide diversity, population divergence, linkage disequilibrium, and the frequency spectrum of mutations from two or more populations. POPBAM can also produce phylogenetic trees of all samples in a BAM file. Finally, I demonstrate that the implementation of POPBAM is both fast and memory-efficient, and also can feasibly scale to the analysis of large BAM files with many individuals and populations. Software The POPBAM program is written in C/C++ and is available from http://dgarriga.github.io/POPBAM . The program has few dependencies and can be built on a variety of Linux platforms. The program is open-source and users are encouraged to participate in the development of this resource

Population Genomics of Secondary Contact

One common form of reticulate evolution arises as a consequence of secondary contact between previously allopatric populations. Using extensive coalescent simulations, we describe the conditions for, and extent of, the introgression of genetic material into the genome of a colonizing population from an endemic population. The simulated coalescent histories are sampled from models that describe the evolution of entire chromosomes, thereby allowing the expected length of introgressed haplotypes to be estimated. The results indicate that our ability to identify reticulate evolution from genetic data is highly variable and depends critically upon the duration of the period of allopatry, the timing of the secondary contact event, as well as the sizes of the populations at the time of contact. One particularly interesting result arises when secondary contact occurs close to the time of a severe founder event, in this case, genetic introgression can be substantially more difficult to detect. However, if secondary contact occurs after such a founding event, when the range of the colonizing population increases, introgression is more readily detectable across the genome. This result may have important implications for our ability to detect introgression between ancestrally bottlenecked modern human populations and archaic hominin species, such as Neanderthals

Evolutionary genomics of piRNA mediated transposon silencing in Drosophila

Thesis (Ph. D.)--University of Rochester. Department of Biology, 2016.Transposable elements (TEs) are abundant throughout the genomes of most living organisms. A recently identified piwi-interacting RNA (piRNA) pathway has been shown to defend against TEs in the Drosophila germline. This dissertation research is an evolutionary genomic analysis of the piRNA pathway in closely related Drosophila species. In Chapter 1, we characterize the rate of evolution for proteins affecting 26 RNAi knockdown phenotypes, which include three phenotypes related to regulation of transposon integration. When RNAi phenotypes are grouped into categories according to cellular function, we find that genes involved in the greatest number of phenotypic categories are also significantly more likely to have a history of rapid protein evolution. Defining pleiotropy using phenotypic categories yields different results than studies that define pleiotropy based on physical interactions. In Chapter 2, we characterize the expression diversity of several families of TEs using piRNAs. Comparative genomic analysis of piRNA expression finds dynamic changes in expression levels of several families of TEs in D. melanogaster and the D. simulans clade. Measuring ping-pong activity— a signature of piRNA amplification finds higher mean piRNA amplification in D. simulans and D. mauritiana, suggesting increased activity of several TEs in these species compared to D. melanogaster. Furthermore, McDonald-Kreitman tests identify three genes in the piRNA pathway as having experienced recent positive selection in D. simulans, and one gene each in D. melanogaster and D. mauritiana. All four genes are components of nuage, which is a macromolecular complex that mediate protein-protein and protein-RNA interactions. Our results are consistent with a model of antagonistic co-evolution between TEs and the piRNA pathway. In Chapter 3, we use single-molecule sequencing to perform a detailed comparative analysis of the flamenco piRNA cluster in both D. melanogaster and D. mauritiana. Our analysis reveals that there is very little sequence homology of flamenco between the two species, indicating rapid turnover of TE sequence. Furthermore, spatial heterogeneity in piRNA abundance in the flamenco region identifies two putative piRNA clusters adjacent to flamenco that may be functionally distinct. This study is the first practical demonstration of re-constructing the genome sequence of highly repetitive piRNA clusters in closely related Drosophila species