相关论文: Population Genetics of Rare Variants and Complex D…

Human populations have undergone dramatic changes in population size in the past 100,000 years, including a severe bottleneck of non-African populations and recent explosive population growth. There is currently great interest in how these…

Population genetic studies have found evidence for dramatic population growth in recent human history. It is unclear how this recent population growth, combined with the effects of negative natural selection, has affected patterns of…

Some species exhibit very high levels of DNA sequence variability; there is also evidence for the existence of heritable epigenetic variants that experience state changes at a much higher rate than sequence variants. In both cases, the…

It is widely recognized nowadays that complex diseases are caused by, amongst the others, multiple genetic factors. The recent advent of genome-wide association study (GWA) has triggered a wave of research aimed at discovering genetic…

Human populations have experienced dramatic growth since the Neolithic revolution. Recent studies that sequenced a very large number of individuals observed an extreme excess of rare variants, and provided clear evidence of recent rapid…

In order to analyze data from cancer genome sequencing projects, we need to be able to distinguish causative, or "driver," mutations from "passenger" mutations that have no selective effect. Toward this end, we prove results concerning the…

Most non-synonymous mutations are thought to be deleterious because of their effect on protein sequence. These polymorphisms are expected to be removed or kept at low frequency by the action of natural selection, and rare deleterious…

Recent studies have shown that human populations have experienced a complex demographic history, including a recent epoch of rapid population growth that led to an excess in the proportion of rare genetic variants in humans today. This…

The selection pressures that have shaped the evolution of complex traits in humans remain largely unknown, and in some contexts highly contentious, perhaps above all where they concern mean trait differences among groups. To date, the…

Evolution has fascinated quantitative and physical scientists for decades: how can the random process of mutation, recombination, and duplication of genetic information generate the diversity of life? What determines the rate of evolution?…

Genetic association data from national biobanks and large-scale association studies have provided new prospects for understanding the genetic evolution of complex traits and diseases in humans. In turn, genomes from ancient human…

To learn about the past from a sample of genomic sequences, one needs to understand how evolutionary processes shape genetic diversity. Most population genetic inference is based on frameworks assuming adaptive evolution is rare. But if…

A major aim of evolutionary biology is to explain the respective roles of adaptive versus non-adaptive changes in the evolution of complexity. While selection is certainly responsible for the spread and maintenance of complex phenotypes,…

Identifying the complete set of functional elements within the human genome would be a windfall for multiple areas of biological research including medicine, molecular biology, and evolution. Complete knowledge of function would aid in the…

Genetic diversity is central to the process of evolution. Both natural selection and random genetic drift are influenced by the level of genetic diversity of a population; selection acts on diversity while drift samples from it. At a given…

Neutral evolution assumes that there are no selective forces distinguishing different variants in a population. Despite this striking assumption, many recent studies have sought to assess whether neutrality can provide a good description of…

The comparative genomics revolution of the past decade has enabled the discovery of functional elements in the human genome via sequence comparison. While that is so, an important class of elements, those specific to humans, is entirely…

We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher…

Recurrent mutations are a common phenomenon in population genetics. They may be at the origin of the fixation of a new genotype, if they give a phenotypic advantage to the carriers of the new mutation. In this paper, we are interested in…

Large populations may contain numerous simultaneously segregating polymorphisms subject to natural selection. Since selection acts on individuals whose fitness depends on many loci, different loci affect each other's dynamics. This leads to…