From Many, One: Genetic Control of Prolificacy during Maize Domestication
David M. Wills, Clinton Whipple, Shohei Takuno, Lisa E. Kursel, Laura M. Shannon, Jeffrey Ross-Ibarra, John F. Doebley
(Submitted on 4 Mar 2013)
A reduction in number and an increase in size of inflorescences is a common aspect of plant domestication. When maize was domesticated from teosinte, the number and arrangement of ears changed dramatically. Teosinte has long lateral branches that bear multiple small ears at their nodes and tassels at their tips. Maize has much shorter lateral branches that are tipped by a single large ear with no additional ears at the branch nodes. To investigate the genetic basis of this difference in prolificacy (the number of ears on a plant), we performed a genome-wide QTL scan. A large effect QTL for prolificacy (prol1.1) was detected on the short arm of chromosome one in a location that has previously been shown to influence multiple domestication traits. We fine-mapped prol1.1 to a 2.7 kb interval or causative region upstream of the grassy tillers1 gene, which encodes a homeodomain leucine zipper transcription factor. Tissue in situ hybridizations reveal that the maize allele of prol1.1 is associated with up-regulation of gt1 expression in the nodal plexus. Given that maize does not initiate secondary ear buds, the expression of gt1 in the nodal plexus in maize may suppress their initiation. Population genetic analyses indicate positive selection on the maize allele of prol1.1, causing a partial sweep that fixed the maize allele throughout most of domesticated maize. This work shows how a subtle cis-regulatory change in tissue specific gene expression altered plant architecture in a way that improved the harvestability of maize.
Soft selective sweeps are the primary mode of recent adaptation in Drosophila melanogaster
Nandita R. Garud, Philipp W. Messer, Erkan O. Buzbas, Dmitri A. Petrov
(Submitted on 5 Mar 2013)
Adaptation is often thought to leave the signature of a hard selective sweep, in which a single haplotype bearing the beneficial allele reaches high population frequency. However, an alternative and often-overlooked scenario is that of a soft selective sweep, in which multiple adaptive haplotypes sweep through the population simultaneously. Soft selective sweeps are likely either when adaptation proceeds from standing genetic variation or in large populations where adaptation is not mutation-limited. Current statistical methods are not well designed to test for soft sweeps, and thus are likely to miss these possibly numerous adaptive events because they look for characteristic reductions in heterozygosity. Here, we developed a statistical test based on a haplotype statistic, H12, capable of detecting both hard and soft sweeps with similar power. We used H12 to identify multiple genomic regions that have undergone recent and strong adaptation using a population sample of fully sequenced Drosophila melanogaster strains (DGRP). We then developed a second statistical test based on a statistic H2/H1 | H12, to test whether a given selective sweep detected by H12 is hard or soft. Surprisingly, when applying the test based on H2/H1 | H12 to the top 50 most extreme H12 candidates in the DGRP data, we reject the hard sweep hypothesis in every case. In contrast, all 50 cases show strong support (Bayes Factor >10) for a soft sweep model. Our results suggest that recent adaptation in North American populations of D. melanogaster has led primarily to soft sweeps either because it utilized standing genetic variation or because the short-term effective population size in D. melanogaster is on the order of billions or larger.
Comprehensive Detection of Genes Causing a Phenotype using Phenotype Sequencing and Pathway Analysis
Marc Harper, Luisa Gronenberg, James Liao, Christopher Lee
(Submitted on 3 Mar 2013)
Discovering all the genetic causes of a phenotype is an important goal in functional genomics. In this paper we combine an experimental design for multiple independent detections of the genetic causes of a phenotype, with a high-throughput sequencing analysis that maximizes sensitivity for comprehensively identifying them. Testing this approach on a set of 24 mutant strains generated for a metabolic phenotype with many known genetic causes, we show that this pathway-based phenotype sequencing analysis greatly improves sensitivity of detection compared with previous methods, and reveals a wide range of pathways that can cause this phenotype. We demonstrate our approach on a metabolic re-engineering phenotype, the PEP/OAA metabolic node in E. coli, which is crucial to a substantial number of metabolic pathways and under renewed interest for biofuel research. Out of 2157 mutations in these strains, pathway-phenoseq discriminated just five gene groups (12 genes) as statistically significant causes of the phenotype. Experimentally, these five gene groups, and the next two high-scoring pathway-phenoseq groups, either have a clear connection to the PEP metabolite level or offer an alternative path of producing oxaloacetate (OAA), and thus clearly explain the phenotype. These high-scoring gene groups also show strong evidence of positive selection pressure, compared with strictly neutral selection in the rest of the genome.
Hybrid-Lambda: simulation of multiple merger and Kingman gene genealogies in species networks and species trees
Sha Zhu, James H Degnan, Bjarki Eldon
(Submitted on 4 Mar 2013)
Hybrid-Lambda is a software package that simulates gene trees under Kingman or two Lambda-coalescent processes within species networks or species trees. It is written in C++, and re- leased under GNU General Public License (GPL) version 3. Users can modify and make new dis- tribution under the terms of this license. For details of this license, visit this http URL. Hybrid Lambda is available at this https URL.
Deleterious synonymous mutations hitchhike to high frequency in HIV-1 env evolution
Fabio Zanini, Richard A. Neher
(Submitted on 4 Mar 2013)
Intrapatient HIV-1 evolution is dominated by selection on the protein level in the arms race with the adaptive immune system. When cytotoxic CD8+ T-cells or neutralizing antibodies target a new epitope, the virus often escapes via nonsynonymous mutations that impair recognition. Synonymous mutations do not affect this interplay and are often assumed to be neutral. We analyze longitudinal intrapatient data from the C2-V5 part of the envelope gene (env) and observe that synonymous derived alleles rarely fix even though they often reach high frequencies in the viral population. We find that synonymous mutations that disrupt base pairs in RNA stems flanking the variable loops of gp120 are more likely to be lost than other synonymous changes, hinting at a direct fitness effect of these stem-loop structures in the HIV-1 RNA. Computational modeling indicates that these synonymous mutations have a (Malthusian) selection coefficient of the order of -0.002 and that they are brought up to high frequency by hitchhiking on neighboring beneficial nonsynonymous alleles. The patterns of fixation of nonsynonymous mutations estimated from the longitudinal data and comparisons with computer models suggest that escape mutations in C2-V5 are only transiently beneficial, either because the immune system is catching up or because of competition between equivalent escapes.
Gene expression in early Drosophila embryos is highly conserved despite extensive divergence of transcription factor binding
Mathilde Paris, Tommy Kaplan, Xiao Yong Li, Jacqueline E. Villalta, Susan E. Lott, Michael B. Eisen
(Submitted on 1 Mar 2013)
To better characterize how variation in regulatory sequences drives divergence in gene expression, we undertook a systematic study of transcription factor binding and gene expression in the blastoderm embryos of four species that sample much of the diversity in the 60 million-year old genus Drosophila: D. melanogaster, D. yakuba, D. pseudoobscura and D. virilis. We compared gene expression, as measured by mRNA-seq to the genome-wide binding of four transcription factors involved in early development, as measured by ChIP-seq (Bicoid, Giant, Hunchback and Kr\”uppel). Surprisingly, we found that mRNA levels are much better conserved than individual binding events. We looked at binding characteristics that may explain such evolutionary disparity. As expected, we found that binding divergence increases with phylogenetic distance. Interestingly, binding events in non-coding regions that were bound strongly by single factors, or bound by multiple factors, were more likely to be conserved. As this class of sites are most likely to be involved in gene regulation, the divergence of other bound regions may simply reflect their lack of function. We used a model of quantitative trait evolution to compare the changes of gene expression with nearby regulatory TF binding. We found that changes in gene expression were poorly explained by changes in associated TF binding. These results suggest that some of the differences in sequence and binding have limited effect on gene expression or act in a compensatory manner to maintain the overall expression levels of regulated genes.
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