An HMM-based Comparative Genomic Framework for Detecting Introgression in Eukaryotes

An HMM-based Comparative Genomic Framework for Detecting Introgression in Eukaryotes
Kevin J. Liu, Jingxuan Dai, Kathy Truong, Ying Song, Michael H. Kohn, Luay Nakhleh
(Submitted on 30 Oct 2013)

One outcome of interspecific hybridization and subsequent effects of evolutionary forces is introgression, which is the integration of genetic material from one species into the genome of an individual in another species. The evolution of several groups of eukaryotic species has involved hybridization, and cases of adaptation through introgression have been already established. In this work, we report on a new comparative genomic framework for detecting introgression in genomes, called PhyloNet-HMM, which combines phylogenetic networks, that capture reticulate evolutionary relationships among genomes, with hidden Markov models (HMMs), that capture dependencies within genomes. A novel aspect of our work is that it also accounts for incomplete lineage sorting and dependence across loci.
Application of our model to variation data from chromosome 7 in the mouse (Mus musculus domesticus) genome detects a recently reported adaptive introgression event involving the rodent poison resistance gene Vkorc1, in addition to other newly detected introgression regions. Based on our analysis, it is estimated that about 12% of all sites withinchromosome 7 are of introgressive origin (these cover about 18 Mbp of chromosome 7, and over 300 genes). Further, our model detects no introgression in two negative control data sets. Our work provides a powerful framework for systematic analysis of introgression while simultaneously accounting for dependence across sites, point mutations, recombination, and ancestral polymorphism.


Global patterns of sex-biased migrations in humans

Global patterns of sex-biased migrations in humans
Chuan-Chao Wang, Li Jin, Hui Li
(Submitted on 29 Oct 2013)

A series of studies have revealed the among-population components of genetic variation are higher for the paternal Y chromosome than for the maternal mitochondrial DNA (mtDNA), which indicates sex-biased migrations in human populations. However, this phenomenon might be also an ascertainment bias due to nonrandom sampling of SNPs. To eliminate the possible bias, we used the whole Y chromosome and mtDNA sequence data of 491 individuals from the 1000 Genomes Project Phase I to address the sex-biased migration dispute. We found that genetic differentiation between populations was higher for Y chromosome than for the mtDNA at global scales. The migration rate of female might be three times higher than that of male, assuming the effective population size is the same for male and female.

Can we predict the mutation rate at the single nucleotide scale in the human genome?

Can we predict the mutation rate at the single nucleotide scale in the human genome?
Adam Eyre-Walker, Ying Chen
(Submitted on 29 Oct 2013)

It has been recently claimed that it is possible to predict the rate of de novo mutation of each site in the human genome with almost perfect accuracy (Michaelson et al. (2012) Cell, 151, 1431-1442). We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show that there could be substantial unexplained variance in the mutation rate. We also demonstrate that the model of Michaelson et al. fails to capture a major component of the variation in the mutation rate, that which is local but not associated with simple context.

Speciation and introgression between Mimulus nasutus and Mimulus guttatus

Speciation and introgression between Mimulus nasutus and Mimulus guttatus
Yaniv Brandvain, Amanda M. Kenney, Lex Flagel, Graham Coop, Andrea L Sweigart
(Submitted on 26 Oct 2013)

Mimulus guttatus and M. nasutus are an evolutionary and ecological model sister species pair differentiated by ecology, mating system, and partial reproductive isolation. Despite extensive research on this system, the history of divergence and differentiation in this sister pair is unclear. We present and analyze a novel population genomic data set which shows that M. nasutus “budded” off of a central Californian M. guttatus population within the last 200 to 500 thousand years. In this time, the M. nasutus genome has accrued numerous genomic signatures of the transition to predominant selfing. Despite clear biological differentiation, we document ongoing, bidirectional introgression. We observe a negative relationship between the recombination rate and divergence between M. nasutus and sympatric M. guttatus samples, suggesting that selection acts against M. nasutus ancestry in M. guttatus.

Fighting network space: it is time for an SQL-type language to filter phylogenetic networks

Fighting network space: it is time for an SQL-type language to filter phylogenetic networks
Steven Kelk, Simone Linz, David A. Morrison
(Submitted on 25 Oct 2013)

The search space of rooted phylogenetic trees is vast and a major research focus of recent decades has been the development of algorithms to effectively navigate this space. However this space is tiny when compared with the space of rooted phylogenetic networks, and navigating this enlarged space remains a poorly understood problem. This, and the difficulty of biologically interpreting such networks, obstructs adoption of networks as tools for modelling reticulation. Here, we argue that the superimposition of biologically motivated constraints, via an SQL-style language, can both stimulate use of network software by biologists and potentially significantly prune the search space.

Discovery of Phylogenetic Relevant Y-chromosome Variants in 1000 Genomes Project Data

Discovery of Phylogenetic Relevant Y-chromosome Variants in 1000 Genomes Project Data
Chuan-Chao Wang, Hui Li
(Submitted on 24 Oct 2013)

Current Y chromosome research is limited in the poor resolution of Y chromosome phylogenetic tree. Entirely sequenced Y chromosomes in numerous human individuals have only recently become available by the advent of next-generation sequencing technology. The 1000 Genomes Project has sequenced Y chromosomes from more than 1000 males. Here, we analyzed 1000 Genomes Project Y chromosome data of 1269 individuals and discovered about 25,000 phylogenetic relevant SNPs. Those new markers are useful in the phylogeny of Y chromosome and will lead to an increased phylogenetic resolution for many Y chromosome studies.

Stochastic dynamics of adaptive trait and neutral marker driven by eco-evolutionary feedbacks

Stochastic dynamics of adaptive trait and neutral marker driven by eco-evolutionary feedbacks
Sylvain Billiard (GEPV), Regis Ferriere (CNRS UMR 7625,), Sylvie Méléard (CMAP), Viet Chi Tran (LPP)
(Submitted on 23 Oct 2013)

How the neutral diversity is affected by selection and adaptation is investigated in an eco-evolutionary framework. In our model, we study a finite population in continuous time, where each individual is characterized by a trait under selection and a completely linked neutral marker. Population dynamics are driven by births and deaths, mutations at birth, and competition between individuals. Trait values influence ecological processes (demographic events, competition), and competition generates selection on trait variation, thus closing the eco-evolutionary feedback loop. The demographic effects of the trait are also expected to influence the generation and maintenance of neutral variation. We consider a large population limit with rare mutation, under the assumption that the neutral marker mutates faster than the trait under selection. We prove the convergence of the stochastic individual-based process to a new measure-valued diffusive process with jumps that we call Substitution Fleming-Viot Process (SFVP). When restricted to the trait space this process is the Trait Substitution Sequence first introduced by Metz et al. (1996). During the invasion of a favorable mutation, a genetical bottleneck occurs and the marker associated with this favorable mutant is hitchhiked. By rigorously analysing the hitchhiking effect and how the neutral diversity is restored afterwards, we obtain the condition for a time-scale separation; under this condition, we show that the marker distribution is approximated by a Fleming-Viot distribution between two trait substitutions. We discuss the implications of the SFVP for our understanding of the dynamics of neutral variation under eco-evolutionary feedbacks and illustrate the main phenomena with simulations. Our results highlight the joint importance of mutations, ecological parameters, and trait values in the restoration of neutral diversity after a selective sweep.

Cryptic Genetic Variation Can Make Irreducible Complexity a Common Mode of Adaptation

Cryptic Genetic Variation Can Make Irreducible Complexity a Common Mode of Adaptation
Meredith V. Trotter, Daniel B. Weissman, Grant I. Peterson, Kayla M. Peck, Joanna Masel
(Submitted on 22 Oct 2013)

The existence of complex (multiple-step) genetic adaptations that are “irreducible” (i.e., all partial combinations are less fit than the original genotype) is one of the longest standing problems in evolutionary biology. In standard genetics parlance, these adaptations require the crossing of a wide adaptive valley of deleterious intermediate stages. Here we demonstrate, using a simple model, that evolution can cross wide valleys to produce “irreducibly complex” adaptations by making use of previously cryptic mutations. When revealed by an evolutionary capacitor, previously cryptic mutants have higher initial frequencies than do new mutations, bringing them closer to a valley-crossing saddle in allele frequency space. Moreover, simple combinatorics imply an enormous number of candidate combinations exist within available cryptic genetic variation. We model the dynamics of crossing of a wide adaptive valley after a capacitance event using both numerical simulations and analytical approximations. Although individual valley crossing events become less likely as valleys widen, by taking the combinatorics of genotype space into account, we see that revealing cryptic variation can cause the frequent evolution of complex adaptations. This finding also effectively dismantles “irreducible complexity” as an argument against evolution by providing a general mechanism for crossing wide adaptive valleys.

Natural selection on human Y chromosomes

Natural selection on human Y chromosomes
Chuan-Chao Wang, Li Jin, Hui Li
(Submitted on 22 Oct 2013)

The paternally inherited Y chromosome has been widely used in population genetic studies to understand relationships among human populations. Our interpretation of Y chromosomal evidence about population history and genetics has rested on the assumption that all the Y chromosomal markers in the male-specific region (MSY) are selectively neutral. However, the very low diversity of Y chromosome has drawn a long debate about whether natural selection has affected this chromosome or not. In recent several years, the progress in Y chromosome sequencing has helped to address this dispute. Purifying selection has been detected in the X-degenerate genes of human Y chromosomes and positive selection might also have an influence in the evolution of testis-related genes in the ampliconic regions. Those new findings remind us to take the effect of natural selection into account when we use Y chromosome in population genetic studies.

Discriminative Measures for Comparison of Phylogenetic Trees

Discriminative Measures for Comparison of Phylogenetic Trees
Omur Arslan, Dan P. Guralnik, Daniel E. Koditschek
(Submitted on 19 Oct 2013)

Efficient and informative comparison of trees is a common essential interest of both computational biology and pattern classification. In this paper, we introduce a novel dissimilarity measure on non-degenerate hierarchies (rooted binary trees), called the NNI navigation distance, that counts the steps along the trajectory of a discrete dynamical system defined over the Nearest Neighbor Interchange(NNI) graph of binary hierarchies. The NNI navigation distance has a unique unifying nature of combining both edge comparison methods and edit operations for comparison of trees and is an efficient approximation to the (NP-hard) NNI distance. It is given by a closed form expression which simply generalizes to nondegenerate hierarchies as well. A relaxation on the closed form of the NNI navigation distance results a simpler dissimilarity measure on all trees, named the crossing dissimilarity, counts pairwise cluster incompatibilities of trees. Both of our dissimilarity measures on nondegenerate hierarchies are positive definite (vanishes only between identical trees) and symmetric but are not a true metric because they do not satisfy the triangle inequality. Although they are not true metrics, they are both linearly bounded below by the widely used Robinson-Foulds metric and above by a new tree metric, called the cluster-cardinality distance — the pullback metric of a matrix norm along an embedding of hierarchies into the space of matrices. All of these proposed tree measures can be efficiently computed in time O(n^2) in the number of leaves, n.