GARD: a genetic algorithm for recombination detection.

Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
Bioinformatics (Impact Factor: 4.62). 01/2007; 22(24):3096-8. DOI: 10.1093/bioinformatics/btl474
Source: PubMed

ABSTRACT Phylogenetic and evolutionary inference can be severely misled if recombination is not accounted for, hence screening for it should be an essential component of nearly every comparative study. The evolution of recombinant sequences can not be properly explained by a single phylogenetic tree, but several phylogenies may be used to correctly model the evolution of non-recombinant fragments.
We developed a likelihood-based model selection procedure that uses a genetic algorithm to search multiple sequence alignments for evidence of recombination breakpoints and identify putative recombinant sequences. GARD is an extensible and intuitive method that can be run efficiently in parallel. Extensive simulation studies show that the method nearly always outperforms other available tools, both in terms of power and accuracy and that the use of GARD to screen sequences for recombination ensures good statistical properties for methods aimed at detecting positive selection.
Freely available


Available from: Simon D W Frost, May 31, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Quantifying intraspecific genetic variation in functionally important genes, such as those of the major histocompatibility complex (MHC), is important in the establishment of conservation plans for endangered species. The MHC genes play a crucial role in the vertebrate immune system and generally show high levels of diversity, which is likely due to pathogen-driven balancing selection. The endangered Blakiston's fish owl (Bubo blakistoni) has suffered marked population declines on Hokkaido Island, Japan, during the past several decades due to human-induced habitat loss and fragmentation. We investigated the spatial and temporal patterns of genetic diversity in MHC class IIβ genes in Blakiston's fish owl, using massively parallel pyrosequencing. Results: We found that the Blakiston's fish owl genome contains at least eight MHC class IIβ loci, indicating recent gene duplications. An analysis of sequence polymorphism provided evidence that balancing selection acted in the past. The level of MHC variation, however, was low in the current fish owl populations in Hokkaido: only 19 alleles were identified from 174 individuals. We detected considerable spatial differences in MHC diversity among the geographically isolated populations. We also detected a decline of MHC diversity in some local populations during the past decades. Conclusions: Our study demonstrated that the current spatial patterns of MHC variation in Blakiston's fish owl populations have been shaped by loss of variation due to the decline and fragmentation of populations, and that the short-term effects of genetic drift have counteracted the long-term effects of balancing selection.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RHDV (rabbit hemorrhagic disease virus), a virulent calicivirus, causes high mortalities in European rabbit populations (Oryctolagus cuniculus). It uses α1,2fucosylated glycans, histo-blood group antigens (HBGAs), as attachment factors, with their absence or low expression generating resistance to the disease. Synthesis of these glycans requires an α1,2fucosyltransferase. In mammals, there are three closely located α1,2fucosyltransferase genes rSec1, rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not suffer gross alterations, although we previously observed that rabbit Sec1 variants present either low or no activity. Still, a low activity rSec1 allele correlated with survival to an RHDV outbreak. We now confirm the association between the α1,2fucosyltransferase loci and survival. In addition, we show that rabbits express homogenous rFut1 and rFut2 levels in the small intestine. Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1 variants detected in wild animals were equally active. Interestingly, rSec1 RNA levels were highly variable between individuals and high expression was associated with low binding of RHDV strains to the mucosa. Co-transfection of rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites, indicating that in rabbits, the catalytically inactive rSec1 protein acts as a dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in leporids, gene conversion analysis showed extensive homogenization between Sec1 and Fut2 in leporids, at variance with its limited degree in other mammals. Gene conversion additionally involving Fut1 was also observed at the C-terminus. Thus, in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a new function with a dominant-negative effect on rFut1, contributing to fucosylated glycan diversity, and allowing herd protection from pathogens such as RHDV.
    PLoS Pathogens 04/2015; 11(4):e1004759. DOI:10.1371/journal.ppat.1004759 · 8.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bats are an ideal mammalian group for exploring adaptations to fasting due to their large variety of diets and because fasting is a regular part of their life cycle. Mammals fed on a carbohydrate-rich diet experience a rapid decrease in blood glucose levels during a fast, thus, the development of mechanisms to resist the consequences of regular fasts, experienced on a daily basis, must have been crucial in the evolution of frugivorous bats. Phosphoenolpyruvate carboxykinase 1 (PEPCK1, encoded by the Pck1 gene) is the rate-limiting enzyme in gluconeogenesis and is largely responsible for the maintenance of glucose homeostasis during fasting in fruit-eating bats. To test whether Pck1 has experienced adaptive evolution in frugivorous bats, we obtained Pck1 coding sequence from 20 species of bats, including five Old World fruit bats (OWFBs) (Pteropodidae) and two New World fruit bats (NWFBs) (Phyllostomidae). Our molecular evolutionary analyses of these sequences revealed that Pck1 was under purifying selection in both Old World and New World fruit bats with no evidence of positive selection detected in either ancestral branch leading to fruit bats. Interestingly, however, six specific amino acid substitutions were detected on the ancestral lineage of OWFBs. In addition, we found considerable evidence for parallel evolution, at the amino acid level, between the PEPCK1 sequences of Old World fruit bats and New World fruit bats. Test for parallel evolution showed that four parallel substitutions (Q276R, R503H, I558V and Q593R) were driven by natural selection. Our study provides evidence that Pck1 underwent parallel evolution between Old World and New World fruit bats, two lineages of mammals that feed on a carbohydrate-rich diet and experience regular periods of fasting as part of their life cycle.
    PLoS ONE 01/2015; 10(3):e0118666. DOI:10.1371/journal.pone.0118666 · 3.53 Impact Factor