Understanding population genetics
Population genetics provides the sharpest analytical tool in biological research. It has a strict mathematical foundation and its results are used in all parts of biology, from simple evolutionary explanations to complex bioinformatics programs for genome analyses.
We are writing a book that introduces the formal side of population genetics by a derivation of ten important results. Working through proofs is an often under-used method to obtain a deeper understanding of an interesting intellectual field. Proof analysis can be made at different levels of ambition – we have tried to present the derivations so that the successive steps can be carefully followed or just glanced over, depending on the needs and interests of the reader. All assumptions that underlie the derivations have been made explicit, so that the reader will know under what conditions the results are applicable and how they can be modified. The ten topics have been chosen to cover a broad range of population genetics using examples of direct biological relevance.
Population genetics of CNV
Copy number variants (CNV), among which are included deletions, insertions and other forms of structural mutations, have received much less attention in genetic analysis than single nucleotide exchanges. Our project aims at detecting and characterizing such mutations in gene families. Several methods are used for their detection, including qPCR and long range PCR. Detected variants are further analyzed with respect to population frequency, number of origins, and age of mutations. At present we are investigating the KLK, WAP and chemokine gene families.
Evolution of genetic systems
Genetics consists of a number of highly integrated and interacting systems. There are systems for keeping down the mutation rate, for organizing recombination, for sex-determination, and so on. All these systems are outcomes of long evolutionary processes. During the last fifty years methods have been developed by which genetic systems can be analyzed according to Darwinian principles. At present most of our interest concerns two questions:
Positive but deteriorating mutations
In elementary population genetics the condition for there to be a balance between mutations and selection is well known. We want to extend the standard results by looking at what happens if the newly induced mutations are positive at first but deteriorate over time. Examples of such mutations are spontaneously generated polyploids, asexual clones, biochemical opportunists that slowly deteriorate their own cellular welfare, mutations causing trinucleotide repeat expansion, and so on. The analyses are done analytically and with computer simulations,
Genomes with optimal size and structure
An organism that incorporates a new gene that gives it an additional biochemical function normally increases its fitness. However, at the same time its genome has become more prone to mutation and various kinds of damage. We are interested in modelling the evolution of genomes when both their expressive functions and material properties are taken into account.
The social history of genetics
Genetics has during the last hundred years strongly affected what we eat, what diseases we can cure, and how we think about ourselves as human beings. Society has, at the same time, had strong effects on what research topics have been genetically investigated. Among various questions concerning the relationship between genetics and society, two will be more deeply researched and their results presented in English.
Origin of the Mendelian Society in Lund
The Mendelian Society in Lund was founded in December 1910 and is thereby perhaps the first genetic society in the world. Its role in the development of Swedish genetics from 1920 to 1960 has been well described, but its start is worth a deeper analysis. This involves, among other aspects, to re-track the lives of its starting members – a fascinating task since they were a most unusual group of people.
Darwin explains Mendel
In the “Modern Evolutionary Synthesis” understanding about evolution was gained by bringing its basic functioning back to simple genetic principles. But where did these simple facts of genetics come from? R. A. Fisher was probably the first who seriously tried to explain a genetic phenomenon (in his case dominance) from Darwinian premises. Such explanations became more common in the 1960s and 1970s, and today all aspects of genetics and genomics are open for Darwinian-based explanations. The intellectual history of how genetics became an object for evolutionary study is worth a serious description.
Mutations in human disease
In cooperation with Christer Halldén, Christina Lind-Hallden, both at HKR, and Stefan Lethagen at Novo-Nordisk/Rigshospitalet Köpenhamn with coworkers, we are involved in an analysis of inherited coagulation disorders. We have identified a series of deletion relating to Protein S deficiency and recently analyzed a Swedish cohort of patients with Type 1 von Willebrand’s Disease. At present we are working on the last disease with a larger sample of patients from all over Europe.