Ola Hössjer

In this paper we study genetic variation at a highly polymorphic locus of a monoecious or dioecious population whose census and effective sizes differ and possibly vary independently over time. More specifically, we develop a general framework for the allele frequency spectrum (AFS) at this locus, and functions of the AFS. Examples of such functions are number of alleles, number of common and rare alleles, allelic diversity, gene diversity, higher order gene diversity and Hill numbers. We develop exact recursions for the expected AFS, and its functionals, with particular interest in populations that experience a rapid (a few generations) bottleneck followed by approaching a new equilibrium between mutation and drift. A grid-based numerical algorithm is developed, which is exact for small populations and approximate for large populations. This algorithm is exemplified with exact calculations for small populations that undergo a bottleneck, and approximate calculations for a moderately large population that rapidly decreases in size.

Current genetics studies often refer to notions from information science. The purpose of this paper is to summarize and structure the different notions of information used in biology, as a step towards developing a taxonomy of information. Within this framework we propose an extension of Floridi’s conceptual model of information. We also make use of the concept of specified information and show that functional information and many other notions of information are either special cases of, or are closely related to, specified information. Since functionality of the proteins that genes code serves as an external and independent specification, this makes it possible to define genetic information in a way that includes semantic aspects. In particular, we discuss how to understand the qualitative aspects of genetic information, how to measure its quantitative aspects, and how variants of Shannon’s information measure can be applied to molecular sequence data of protein families. While a mathematical framework may not be able to incorporate all that is included within biological information, some aspects of it allow for statistical modelling. This is especially true if we restrict our focus on the discipline of genetics. The concept of genetic information is still disputed because it attributes semantic traits to what seems to be regular biochemical entities. Some researchers maintain that the use of information in biology is just metaphorical and may even be misleading. We argue that the foundation of the metaphorical view is relatively weak given the current findings in bioinformatics and show that the present understanding of genetics fits well into the context of the modern philosophy of information. The paper concludes that informational concepts have robust scientific applications at the level of genes.

The variance effective population size (NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document}) is frequently used to quantify the expected rate at which a population’s allele frequencies change over time. The purpose of this paper is to find expressions for the global NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document} of a spatially structured population that are of interest for conservation of species. Since NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document} depends on allele frequency change, we start by dividing the cause of allele frequency change into genetic drift within subpopulations (I) and a second component mainly due to migration between subpopulations (II). We investigate in detail how these two components depend on the way in which subpopulations are weighted as well as their dependence on parameters of the model such a migration rates, and local effective and census sizes. It is shown that under certain conditions the impact of II is eliminated, and NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document} of the metapopulation is maximized, when subpopulations are weighted proportionally to their long term reproductive contributions. This maximal NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document} is the sought for global effective size, since it approximates the gene diversity effective size NeGD\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eGD}$$\end{document}, a quantifier of the rate of loss of genetic diversity that is relevant for conservation of species and populations. We also propose two novel versions of NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document}, one of which (the backward version of NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document}) is most stable, exists for most populations, and is closer to NeGD\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eGD}$$\end{document} than the classical notion of NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document}. Expressions for the optimal length of the time interval for measuring genetic change are developed, that make it possible to estimate any version of NeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$N_{eV}$$\end{document} with maximal accuracy.

Recently Díaz, Hössjer and Marks (DHM) presented a Bayesian framework to measure cosmological tuning (either fine or coarse) that uses maximum entropy (maxent) distributions on unbounded sample spaces as priors for the parameters of the physical models (https://doi.org/10.1088/1475-7516/2021/07/020). The DHM framework stands in contrast to previous attempts to measure tuning that rely on a uniform prior assumption. However, since the parameters of the models often take values in spaces of infinite size, the uniformity assumption is unwarranted. This is known as the normalization problem. In this paper we explain why and how the DHM framework not only evades the normalization problem but also circumvents other objections to the tuning measurement like the so called weak anthropic principle, the selection of a single maxent distribution and, importantly, the lack of invariance of maxent distributions with respect to data transformations. We also propose to treat fine-tuning as an emergence problem to avoid infinite loops in the prior distribution of hyperparameters (common to all Bayesian analysis), and explain that previous attempts to measure tuning using uniform priors are particular cases of the DHM framework. Finally, we prove a theorem, explaining when tuning is fine or coarse for different families of distributions. The theorem is summarized in a table for ease of reference, and the tuning of three physical parameters is analyzed using the conclusions of the theorem.

Unmeasured confounding is an important threat to the validity of observational studies. A common way to deal with unmeasured confounding is to compute bounds for the causal effect of interest, that is, a range of values that is guaranteed to include the true effect, given the observed data. Recently, bounds have been proposed that are based on sensitivity parameters, which quantify the degree of unmeasured confounding on the risk ratio scale. These bounds can be used to compute an E-value, that is, the degree of confounding required to explain away an observed association, on the risk ratio scale. We complement and extend this previous work by deriving analogous bounds, based on sensitivity parameters on the risk difference scale. We show that our bounds can also be used to compute an E-value, on the risk difference scale. We compare our novel bounds with previous bounds through a real data example and a simulation study.