Faculty of 1000 evaluation for Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome.

The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication.

Download Full-text

Background selection as baseline for nucleotide variation across the Drosophila genome

10.1101/005017 ◽

2014 ◽

Author(s):

Josep M Comeron

Keyword(s):

Balancing Selection ◽

Genetic Maps ◽

Drosophila Genome ◽

Background Selection ◽

Deleterious Mutations ◽

Entire Genome ◽

Genome Wide ◽

Intergenic Regions ◽

Selection Parameters ◽

Genomic Regions

The constant removal of deleterious mutations by natural selection causes a reduction in neutral diversity and efficacy of selection at genetically linked sites (a process called Background Selection, BGS). Population genetic studies, however, often ignore BGS effects when investigating demographic events or the presence of other types of selection. To obtain a more realistic evolutionary expectation that incorporates the unavoidable consequences of deleterious mutations, we generated high-resolution landscapes of variation across the Drosophila melanogaster genome under a BGS scenario independent of polymorphism data. We find that BGS plays a significant role in shaping levels of variation across the entire genome, including long introns and intergenic regions distant from annotated genes. We also find that a very large percentage of the observed variation in diversity across autosomes can be explained by BGS alone, up to 70% across individual chromosome arms, thus indicating that BGS predictions can be used as baseline to infer additional types of selection and demographic events. This approach allows detecting several outlier regions with signal of recent adaptive events and selective sweeps. The use of a BGS baseline, however, is particularly appropriate to investigate the presence of balancing selection and our study exposes numerous genomic regions with the predicted signature of higher polymorphism than expected when a BGS context is taken into account. Importantly, we show that these conclusions are robust to the mutation and selection parameters of the BGS model. Finally, analyses of protein evolution together with previous comparisons of genetic maps between Drosophila species, suggest temporally variable recombination landscapes and thus, local BGS effects that may differ between extant and past phases. Because genome-wide BGS and temporal changes in linkage effects can skew approaches to estimate demographic and selective events, future analyses should incorporate BGS predictions and capture local recombination variation across genomes and along lineages.

Download Full-text

Faculty Opinions recommendation of Drosophila genome-scale screen for PAN GU kinase substrates identifies Mat89Bb as a cell cycle regulator.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1025034.294776 ◽

2005 ◽

Author(s):

Prasad Jallepalli

Keyword(s):

Cell Cycle ◽

Drosophila Genome ◽

Cell Cycle Regulator ◽

A Cell ◽

Kinase Substrates ◽

Genome Scale

Download Full-text

Balancing Selection on Electrophoretic Variation of Phosphoglucose Isomerase in Two Species of Field Cricket: Gryllus veletis and G. pennsylvanicus

Genetics ◽

10.1093/genetics/147.2.609 ◽

1997 ◽

Vol 147 (2) ◽

pp. 609-621

Author(s):

Laura A Katz ◽

Richard G Harrison

Keyword(s):

Balancing Selection ◽

Emergent Property ◽

Phosphoglucose Isomerase ◽

Field Cricket ◽

Nucleotide Variation ◽

Eastern United States ◽

Electrophoretic Variation ◽

Sympatric Populations ◽

Field Crickets ◽

Gryllus Veletis

Two species of crickets, Gryllus veletis and G. pennsylvanicus, share six electrophoretic mobility classes for the enzyme phosphoglucose isomerase (PGI), despite evidence from other genetic markers that the two species are not closely related within eastern North American field crickets. Moreover, the frequencies of the two most common PGI electrophoretic classes (PGI-100 and PGI-65) covary in sympatric populations of these species in the eastern United States, suggesting that PGI may be subject to trans-specific balancing selection. To determine the molecular basis of the electrophoretic variation, we characterized the DNA sequence of the Pgi gene from 29 crickets (15 G. veletis and 14 G. pennsylvanicus). Amino acid substitutions that distinguish the electrophoretic classes are not the same in the two species, and there is no evidence that specific replacement substitutions represent trans-specific polymorphism. In particular, the amino acids that diagnose the PGI-65 allele relative to the PGI-100 allele differ both between G. veletis and G. pennsylvanicus and within G. pennsylvanicus. The heterogeneity among electrophoretic classes that covary in sympatric populations coupled with analysis of patterns of nucleotide variation suggest that Pgi is not evolving neutrally. Instead, the data are consistent with balancing selection operating on an emergent property of the PGI protein.

Download Full-text

Interactions Between Natural Selection, Recombination and Gene Density in the Genes of Drosophila

Genetics ◽

10.1093/genetics/160.2.595 ◽

2002 ◽

Vol 160 (2) ◽

pp. 595-608 ◽

Cited By ~ 17

Author(s):

Jody Hey ◽

Richard M Kliman

Keyword(s):

Gene Expression ◽

Natural Selection ◽

Recombination Rate ◽

Codon Bias ◽

Gene Density ◽

Drosophila Genome ◽

Functional Variation ◽

Subtle Effect ◽

Efficiency Of Selection ◽

The Impact

AbstractIn Drosophila, as in many organisms, natural selection leads to high levels of codon bias in genes that are highly expressed. Thus codon bias is an indicator of the intensity of one kind of selection that is experienced by genes and can be used to assess the impact of other genomic factors on natural selection. Among 13,000 genes in the Drosophila genome, codon bias has a slight positive, and strongly significant, association with recombination—as expected if recombination allows natural selection to act more efficiently when multiple linked sites segregate functional variation. The same reasoning leads to the expectation that the efficiency of selection, and thus average codon bias, should decline with gene density. However, this prediction is not confirmed. Levels of codon bias and gene expression are highest for those genes in an intermediate range of gene density, a pattern that may be the result of a tradeoff between the advantages for gene expression of close gene spacing and disadvantages arising from regulatory conflicts among tightly packed genes. These factors appear to overlay the more subtle effect of linkage among selected sites that gives rise to the association between recombination rate and codon bias.

Download Full-text

Genetic and Molecular Analysis of Region 88E9;88F2 in Drosophila melanogaster, Including the ear Gene Related to Human Factors Involved in Lineage-Specific Leukemias

Genetics ◽

10.1093/genetics/160.3.1051 ◽

2002 ◽

Vol 160 (3) ◽

pp. 1051-1065

Author(s):

Claudia B Zraly ◽

Yun Feng ◽

Andrew K Dingwall

Keyword(s):

Large Scale ◽

Drosophila Genome ◽

Embryonic Cells ◽

Ems Mutagenesis ◽

Recessive Lethal ◽

Protein Levels ◽

Late Embryogenesis ◽

Complementation Groups ◽

Mammalian Genes ◽

Map Location

Abstract We identified and characterized the Drosophila gene ear (ENL/AF9-related), which is closely related to mammalian genes that have been implicated in the onset of acute lymphoblastic and myelogenous leukemias when their products are fused as chimeras with those of human HRX, a homolog of Drosophila trithorax. The ear gene product is present in all early embryonic cells, but becomes restricted to specific tissues in late embryogenesis. We mapped the ear gene to cytological region 88E11-13, near easter, and showed that it is deleted by Df(3R)ea5022rx1, a small, cytologically invisible deletion. Annotation of the completed Drosophila genome sequence suggests that this region might contain as many as 26 genes, most of which, including ear, are not represented by mutant alleles. We carried out a large-scale noncom-plementation screen using Df(3R)ea5022rx1 and chemical (EMS) mutagenesis from which we identified sevenc novel multi-allele recessive lethal complementation groups in this region. An overlapping deficiency, Df(3R)Po4, allowed us to map several of these groups to either the proximal or the distal regions of Df(3R)ea5022rx1. One of these complementation groups likely corresponds to the ear gene as judged by map location, terminal phenotype, and reduction of EAR protein levels.

Download Full-text

Sensitive analysis of single nucleotide variation by Cas13d orthologs, EsCas13d and RspCas13d

Biotechnology and Bioengineering ◽

10.1002/bit.27813 ◽

2021 ◽

Author(s):

Xin Qiao ◽

Yanmin Gao ◽

Jiaojiao Li ◽

Zhaoguan Wang ◽

Hongyan Qiao ◽

...

Keyword(s):

Nucleotide Variation ◽

Single Nucleotide Variation ◽

Single Nucleotide ◽

Sensitive Analysis

Download Full-text

Large-Scale Adaptive Hitchhiking Upon High Recombination inDrosophila simulans

Genetics ◽

10.1093/genetics/165.2.895 ◽

2003 ◽

Vol 165 (2) ◽

pp. 895-900 ◽

Cited By ~ 10

Author(s):

Humberto Quesada ◽

Ursula E M Ramírez ◽

Julio Rozas ◽

Montserrat Aguadé

Keyword(s):

Genetic Linkage ◽

Large Scale ◽

Intermediate Frequency ◽

Core Region ◽

Adaptive Mutation ◽

Nucleotide Variation ◽

Extended Haplotype ◽

Major Haplotype ◽

Pattern Of Variation

AbstractNatural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining ∼88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the ∼88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.

Download Full-text