Phylogenetic Mapping of Recombination Hotspots in Human Immunodeficiency Virus via Spatially Smoothed Change-Point Processes

Abstract

We present a Bayesian framework for inferring spatial preferences of recombination from multiple putative recombinant nucleotide sequences. Phylogenetic recombination detection has been an active area of research for the last 15 years. However, only recently attempts to summarize information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination breakpoint locations and spatial variation in recombination frequency. The dual multiple change-point model for phylogenetic recombination detection resides at the lowest level of our hierarchy under the umbrella of a common prior on breakpoint locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual data sets. To overcome the sparseness of breakpoint data, dictated by the modest number of available recombinant sequences, we a priori impose a biologically relevant correlation structure on recombination location log odds via a Gaussian Markov random field hyperprior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of breakpoint locations. We then proceed with the analysis of 42 human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a putative recombination hotspot.

Recombination in viruses: Mechanisms, methods of study, and evolutionary consequences

“…The identification of recombination breakpoints in viruses is useful to detect circulating recombinant forms (Minin et al, 2007;Archer et al, 2008), to study adaptive recombination (Monjane et al, 2011), to analyze recombinant data (Kosakovsky Pond et al, 2006a;Arenas and Posada, 2010c;Arenas, 2013b), and to infer the underlying mechanisms of recombination. Recombination is generally non-homogeneous along genomes (Minin et al, 2007;Monjane et al, 2011). A number of programs exist to detect recombination breakpoints (Martin et al, 2011a,b), but some of them are more commonly used because of their high accuracy and user-friendly environment.…”

Ecosystem simplification, biodiversity loss and plant virus emergence

“…Little is known about the selective forces that drive viral evolution in natural ecosystems, which contrasts with the more detailed population genetics studies in crop plants that have revealed the importance of mutation rates [36,37], recombination [38][39][40], genetic drift [1 ], and, to a lesser extent, migration in virus evolution. In recent years, the methodology of phylogenetic inference, relying on maximum likelihood, Bayesian and other quantitative frameworks, has made great strides and started to unravel life histories of viruses with a sensitivity not attainable previously [36,[41][42][43][44][45][46]. Approaches based on the coalescent theory and other statistical models have been developed [47][48][49], allowing investigators to quantify the effects of the individual evolutionary factors, including particularly revealing results on positive vs. purifying selection, interhost vs. intrahost evolution patterns, etc.…”

Quantitative Trait Loci (QTL) Analysis For Rice Grain Width and Fine Mapping of an Identified QTL Allele gw-5 in a Recombination Hotspot Region on Chromosome 5

“…This novel finding creates an opportunity, as well as poses a challenge, for molecular geneticists in the further exploration of the relationship between fine structure and crossover frequency of rice chromosomes by dissecting the mechanism of high recombination frequencies in the four regions surrounding the gw-5 gene between the two parents (Asominori and CSSL28). Similarly, linkage mapping strategies have been used to investigate the recombination hotspots on chromosomes of a wide variety of organisms, e.g., wheat (Faris et al 2000), neurospora (Yeadon et al 2004), mouse (Kelmenson et al 2005), and human (Minin et al 2007). …”