A Wright-Fisher graph model and the impact of directional selection on genetic variation

We introduce a multi-allele Wright-Fisher model with non-recurrent, reversible mutation and directional selection. In this setting, the allele frequencies at a single locus track the path of a hybrid jump-diffusion process with state space given by the vertex and edge set of a graph. Vertices represent monomorphic population states and edge-positions mark the biallelic proportions of ancestral and derived alleles during polymorphic segments. We derive the stationary distribution in mutation-selection-drift equilibrium and obtain the expected allele frequency spectrum under large population size scaling. For the extended model with multiple independent loci we derive rigorous upper bounds for a wide class of associated measures of genetic variation. Within this framework we present mathematically precise arguments to conclude that the presence of directional selection reduces the magnitude of genetic variation, as constrained by the bounds for neutral evolution

Tunkeutumisenesto ja havainnointi käytönvalvontajärjestelmissä

Tässä insinöörityössä tutkittiin tunkeutumisenesto- ja havainnointijärjestelmien soveltuvuutta nykyaikaisiin käytönvalvontajärjestelmiin. Työ tehtiin Helsingin Energialle, joka on merkittävä energiapalveluita tarjoava yritys Suomessa. Työssä perehdyttiin ensin teoreettisella tasolla käytönvalvontajärjestelmien arkkitehtuuriin, komponentteihin ja tietoturvavaatimuksiin. Lisäksi tutustuttiin yleisimpiin käytössä oleviin käytönvalvontaprotokolliin ja niiden rakenteisiin. Tämän jälkeen työssä selvitettiin tunkeutumisenesto- ja havainnointitekniikoiden toimintaa sekä suunnittelun perusteita. Tämä insinöörityö tuotti myös käytönvalvontajärjestelmiin suunnitellun tunkeutumisenesto- ja havainnointijärjestelmän vaatimusmäärittelyn ja toteutussuunnitelman. Työn tuloksena todettiin tunkeutumisenesto- ja havainnointijärjestelmien protokollakuvauksien tarjonnan olevan niukkaa Pohjoismaissa käytetyille käytönvalvontaprotokollille. Lisäksi kuvausten käyttöönottoon tulee suhtautua varauksella järjestelmien kriittisyyden vuoksi. IDPS-järjestelmien todettiin kuitenkin nostavan käytönvalvontajärjestelmien tieto-turvatasoa muilla ominaisuuksillaan. Työssä painotettiin lisäksi tunkeutumisenesto- ja havainnointijärjestelmän integroinnin tärkeyttä ylläpito- ja hallintaprosesseihin, sekä elinkaaresta huolehtimista.The purpose of this study was to research possibilities for implementing intrusion prevention and detection systems into modern SCADA networks. This study was carried out for Helsinki Energy, a significant energy service provider in Finland. The first part discusses the architecture of SCADA networks, its components and data security requirements on a theoretical level, as well as the most common SCADA protocols and structures. The second part studies the function of intrusion prevention and detection and the basis for its design. This study also defined the requirements as well as laid out an implementation plan for intrusion prevention and detection in SCADA networks. The results of this study show that the supply of intrusion prevention and detection protocol filters is insufficient for SCADA networks used in the Nordic countries. Furthermore, the implementation of protocol filters must be viewed critically. Nevertheless, the IDPS systems still seem to raise the data security level of SCADA networks. It was concluded that the integration of intrusion prevention and detection into maintenance and management practice is as important as the lifecycle. This study was successful in defining the requirements as well as in creating an implementation plan for intrusion prevention and detection in SCADA networks

Covariation in levels of nucleotide diversity in homologous regions of the avian genome long after completion of lineage sorting

Closely related species may show similar levels of genetic diversity in homologous regions of the genome owing to shared ancestral variation still segregating in the extant species. However, after completion of lineage sorting, such covariation is not necessarily expected. On the other hand, if the processes that govern genetic diversity are conserved, diversity may potentially covary even among distantly related species. We mapped regions of conserved synteny between the genomes of two divergent bird speciescollared flycatcher and hooded crow-and identified more than 600 Mb of homologous regions (66% of the genome). From analyses of whole-genome resequencing data in large population samples of both species we found nucleotide diversity in 200 kb windows to be well correlated (Spearman's rho = 0.407). The correlation remained highly similar after excluding coding sequences. To explain this covariation, we suggest that a stable avian karyotype and a conserved landscape of recombination rate variation render the diversity-reducing effects of linked selection similar in divergent bird lineages. Principal component regression analysis of several potential explanatory variables driving heterogeneity in flycatcher diversity levels revealed the strongest effects from recombination rate variation and density of coding sequence targets for selection, consistent with linked selection. It is also possible that a stable karyotype is associated with a conserved genomic mutation environment contributing to covariation in diversity levels between lineages. Our observations imply that genetic diversity is to some extent predictable

Molecular evolution of genes in avian genomes

Nam K, Mugal C, Nabholz B, et al. Molecular evolution of genes in avian genomes. Genome Biology. 2010;11(6): R68.Background: Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species. Results: We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an overrepresentation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton. Conclusions: Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between ω and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes

Nucleotide Substitution Patterns in Vertebrate Genomes

The rates and patterns at which nucleotide substitutions occur vary significantly across the genome sequence of vertebrates. A prominent example is the difference in the rate of evolution of functional sequences versus nonfunctional (neutrally evolving) sequences, which is explained by the influence of natural selection on functional sequences. However, even within neutrally evolving sequences there is striking variation in the rates and patterns of nucleotide substitutions. Unraveling the underlying processes that induce this variation is necessary to understand the basic principles of variation in neutral substitution profiles, which in turn is crucial for the identification of regions in the genome where natural selection acts. This research question builds the main focus of the present thesis. I have studied the causes and consequences of variation in different patterns of nucleotide substitutions. In particular, I have investigated substitutional strand asymmetries in mammalian genes and could show that they result from the asymmetric nature of DNA replication and transcription. Comparative analysis of substitutional asymmetries then suggested that the organization of DNA replication and the level of transcription are conserved among mammals. Further, I have examined the variation in CpG mutation rate among human genes and could show that beside DNA methylation also GC content plays a decisive role in CpG mutability. In addition, I have studied the signatures of GC-biased gene conversion and its impact on the evolution of the GC isochore structure in chicken. By comparison of the results in chicken to previous results in human I found evidence that karyotype stability is critical for the evolution of GC isochores. Finally, beside the empirical studies, I have performed theoretical investigations of substitution rates in functional sequences. More precisely, I have explored the temporal dynamics of estimates of the ratio of non-synonymous to synonymous substitution rates dN/dS in a phylogentic-population genetic framework.

Nucleotide Substitution Patterns in Vertebrate Genomes

The rates and patterns at which nucleotide substitutions occur vary significantly across the genome sequence of vertebrates. A prominent example is the difference in the rate of evolution of functional sequences versus nonfunctional (neutrally evolving) sequences, which is explained by the influence of natural selection on functional sequences. However, even within neutrally evolving sequences there is striking variation in the rates and patterns of nucleotide substitutions. Unraveling the underlying processes that induce this variation is necessary to understand the basic principles of variation in neutral substitution profiles, which in turn is crucial for the identification of regions in the genome where natural selection acts. This research question builds the main focus of the present thesis. I have studied the causes and consequences of variation in different patterns of nucleotide substitutions. In particular, I have investigated substitutional strand asymmetries in mammalian genes and could show that they result from the asymmetric nature of DNA replication and transcription. Comparative analysis of substitutional asymmetries then suggested that the organization of DNA replication and the level of transcription are conserved among mammals. Further, I have examined the variation in CpG mutation rate among human genes and could show that beside DNA methylation also GC content plays a decisive role in CpG mutability. In addition, I have studied the signatures of GC-biased gene conversion and its impact on the evolution of the GC isochore structure in chicken. By comparison of the results in chicken to previous results in human I found evidence that karyotype stability is critical for the evolution of GC isochores. Finally, beside the empirical studies, I have performed theoretical investigations of substitution rates in functional sequences. More precisely, I have explored the temporal dynamics of estimates of the ratio of non-synonymous to synonymous substitution rates dN/dS in a phylogentic-population genetic framework.

A systematic approach to the study of GC-biased gene conversion in mammals

A recommendation – based on reviews by Fanny Pouyet, David Castellano and one anonymous reviewer – of the article: Galtier N (2021) Fine-scale quantification of GC-biased gene conversion intensity in mammals. bioRxiv, 2021.05.05.442789, ver. 5 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2021.05.05.44278

Nucleotide Substitution Patterns in Vertebrate Genomes

The rates and patterns at which nucleotide substitutions occur vary significantly across the genome sequence of vertebrates. A prominent example is the difference in the rate of evolution of functional sequences versus nonfunctional (neutrally evolving) sequences, which is explained by the influence of natural selection on functional sequences. However, even within neutrally evolving sequences there is striking variation in the rates and patterns of nucleotide substitutions. Unraveling the underlying processes that induce this variation is necessary to understand the basic principles of variation in neutral substitution profiles, which in turn is crucial for the identification of regions in the genome where natural selection acts. This research question builds the main focus of the present thesis. I have studied the causes and consequences of variation in different patterns of nucleotide substitutions. In particular, I have investigated substitutional strand asymmetries in mammalian genes and could show that they result from the asymmetric nature of DNA replication and transcription. Comparative analysis of substitutional asymmetries then suggested that the organization of DNA replication and the level of transcription are conserved among mammals. Further, I have examined the variation in CpG mutation rate among human genes and could show that beside DNA methylation also GC content plays a decisive role in CpG mutability. In addition, I have studied the signatures of GC-biased gene conversion and its impact on the evolution of the GC isochore structure in chicken. By comparison of the results in chicken to previous results in human I found evidence that karyotype stability is critical for the evolution of GC isochores. Finally, beside the empirical studies, I have performed theoretical investigations of substitution rates in functional sequences. More precisely, I have explored the temporal dynamics of estimates of the ratio of non-synonymous to synonymous substitution rates dN/dS in a phylogentic-population genetic framework.