Joint estimation of gene conversion rates and mean conversion tract lengths from population SNP data

Motivation: Two known types of meiotic recombination are crossovers and gene conversions. Although they leave behind different footprints in the genome, it is a challenging task to tease apart their relative contributions to the observed genetic variation. In particular, for a given population SNP dataset, the joint estimation of the crossover rate, the gene conversion rate and the mean conversion tract length is widely viewed as a very difficult problem

Fine Scale Analysis of Crossover and Non-Crossover and Detection of Recombination Sequence Motifs in the Honeybee (Apis mellifera)

BACKGROUND: Meiotic exchanges are non-uniformly distributed across the genome of most studied organisms. This uneven distribution suggests that recombination is initiated by specific signals and/or regulations. Some of these signals were recently identified in humans and mice. However, it is unclear whether or not sequence signals are also involved in chromosomal recombination of insects. METHODOLOGY: We analyzed recombination frequencies in the honeybee, in which genome sequencing provided a large amount of SNPs spread over the entire set of chromosomes. As the genome sequences were obtained from a pool of haploid males, which were the progeny of a single queen, an oocyte method (study of recombination on haploid males that develop from unfertilized eggs and hence are the direct reflect of female gametes haplotypes) was developed to detect recombined pairs of SNP sites. Sequences were further compared between recombinant and non-recombinant fragments to detect recombination-specific motifs. CONCLUSIONS: Recombination events between adjacent SNP sites were detected at an average distance of 92 bp and revealed the existence of high rates of recombination events. This study also shows the presence of conversion without crossover (i. e. non-crossover) events, the number of which largely outnumbers that of crossover events. Furthermore the comparison of sequences that have undergone recombination with sequences that have not, led to the discovery of sequence motifs (CGCA, GCCGC, CCGCA), which may correspond to recombination signals

Joint estimation of gene conversion rates and mean conversion tract lengths from population SNP data.

MotivationTwo known types of meiotic recombination are crossovers and gene conversions. Although they leave behind different footprints in the genome, it is a challenging task to tease apart their relative contributions to the observed genetic variation. In particular, for a given population SNP dataset, the joint estimation of the crossover rate, the gene conversion rate and the mean conversion tract length is widely viewed as a very difficult problem.ResultsIn this article, we devise a likelihood-based method using an interleaved hidden Markov model (HMM) that can jointly estimate the aforementioned three parameters fundamental to recombination. Our method significantly improves upon a recently proposed method based on a factorial HMM. We show that modeling overlapping gene conversions is crucial for improving the joint estimation of the gene conversion rate and the mean conversion tract length. We test the performance of our method on simulated data. We then apply our method to analyze real biological data from the telomere of the X chromosome of Drosophila melanogaster, and show that the ratio of the gene conversion rate to the crossover rate for the region may not be nearly as high as previously claimed.AvailabilityA software implementation of the algorithms discussed in this article is available at http://www.cs.berkeley.edu/ approximately yss/software.html

Modeling the demographic history of Drosophila melanogaster using Approximate Bayesian Computation and Next Generation Sequencing Data

The main goal of this thesis was to develop demographic models of the fruit fly Drosophila melanogaster using Approximate Bayesian Computation and Next Generation Sequencing Data. These models were used to reconstruct the history of African, European, and North American populations. Chapter 1 deals with the demographic history of North American D. melanogaster. This project was motivated by the release of full-genome sequences of a North American population, which showed greater diversity than European D. melanogaster although the introduction of the fruit fly to North America dates back to only �200 years ago. Here, we tested di�erent demographic models involving populations of Zimbabwe, The Netherlands, and North Carolina (North America). Among the tested models we included variants with and without migration, as well as a model involving admixture between the population of Africa and Europe that generated the population of North America. We found that the admixture model �ts best the observed data and we estimated the proportion of European and African admixture in the North American population. This population has 85% European and 15% African ancestry. We also estimated other population parameters including population sizes (current and ancestral) and divergence times. Con�cerning previous studies we also estimated the divergence between African and European populations to be around 19,000 years ago. Chapter 2 deals with gene flow of D. melanogaster between African and European populations. Gene flow in D. melanogaster is well acknowledged but has not been quanti�ed using DNA sequence data. Previous studies from the late 80's based on allozymes found that the number of migrants per generation (Nm) was around 2 between several populations distributed worldwide. Here we used ABC methods and full-genome sequences to estimate the rate of migration between a population from Rwanda in Africa and a population from France. We found that Nm is around 10, which may imply there was a signi�cant increase of gene flow in the last few decades. Our estimates show that the migration rate between these two populations is not necessarily symmetrical, with migration from Europe to Africa being higher than the opposite, although the di�erence does not seem to be significant. The study of gene flow is relevant because it constitutes an important force in population genetics. Theoretical studies have shown that, under neutrality, it is enough to have one migrant per generation to stop two populations from diverging and speciating, and if migration is strong enough it can also overcome the e�ect of selection. Chapter 3 focuses on the sequencing of 130 full genomes of D. melanogaster from Africa and 9 from France. This project made use of haploid embryos, a new technique introduced in 2011 that allows the development of haploid D. melanogaster, which is then used for sequencing. The main goal of this project was to characterize these populations in terms of their diversity, admixture, and di�erentiation. We found that the most diverse population comes from Zambia, which is now thought to be much closer to D. melanogaster 's center of origin. We also found a signi�cant amount of non-cosmopolitan admixture in several African populations, meaning that there exists a signi�cant amount of back migration from Europe to Africa (corroborating the fi�ndings of chapter 2). In order to identify admixture tracts a new method was developed for this purpose, which uses a hidden Markov model to locate admixed regions along the genome. Admixed regions, as well as regions showing high levels of identity by descent were masked for downstream population genetics analyses. These full genomes constitute the second e�ort of the Drosophila Population Genomics Project (DPGP 2) and are now available for the scienti�c community