Dataset Information

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.

ABSTRACT: The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.

SUBMITTER: Albert FW

PROVIDER: S-EPMC3183948 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.

Albert F W FW Hodges E E Jensen J D JD Besnier F F Xuan Z Z Rooks M M Bhattacharjee A A Brizuela L L Good J M JM Green R E RE Burbano H A HA Plyusnina I Z IZ Trut L L Andersson L L Schöneberg T T Carlborg O O Hannon G J GJ Pääbo S S

Heredity 20110209 3

The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founde ...[more]

PMID: 21304545

Similar Datasets

Project description:BackgroundNumerous genome-wide scans conducted by genotyping previously ascertained single-nucleotide polymorphisms (SNPs) have provided candidate signatures for positive selection in various regions of the human genome, including in genes involved in pigmentation traits. However, it is unclear how well the signatures discovered by such haplotype-based test statistics can be reproduced in tests based on full resequencing data. Four genes (oculocutaneous albinism II (OCA2), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT), and KIT ligand (KITLG)) implicated in human skin-color variation, have shown evidence for positive selection in Europeans and East Asians in previous SNP-scan data. In the current study, we resequenced 4.7 to 6.7 kb of DNA from each of these genes in Africans, Europeans, East Asians, and South Asians.ResultsApplying all commonly used neutrality-test statistics for allele frequency distribution to the newly generated sequence data provided conflicting results regarding evidence for positive selection. Previous haplotype-based findings could not be clearly confirmed. Although some tests were marginally significant for some populations and genes, none of them were significant after multiple-testing correction. Combined P values for each gene-population pair did not improve these results. Application of Approximate Bayesian Computation Markov chain Monte Carlo based to these sequence data using a simple forward simulator revealed broad posterior distributions of the selective parameters for all four genes, providing no support for positive selection. However, when we applied this approach to published sequence data on SLC45A2, another human pigmentation candidate gene, we could readily confirm evidence for positive selection, as previously detected with sequence-based and some haplotype-based tests.ConclusionsOverall, our data indicate that even genes that are strong biological candidates for positive selection and show reproducible signatures of positive selection in SNP scans do not always show the same replicability of selection signals in other tests, which should be considered in future studies on detecting positive selection in genetic data.

Project description:Natural selection of beneficial genetic variants played a critical role in human adaptation to a wide range of environmental conditions. Northern Eurasia, despite its severe climate, is home to lots of ethnically diverse populations. The genetic variants associated with the survival of these populations have hardly been analyzed. We searched for the genomic signatures of positive selection in (1) the genome-wide microarray data of 432 people from eight different northern Russian populations and (2) the whole-genome sequences of 250 people from Northern Eurasia from a public repository through testing the extended haplotype homozigosity (EHH) and direct comparison of allele frequency, respectively. The 20 loci with the strongest selection signals were characterized in detail. Among the top EHH hits were the NRG3 and NBEA genes, which are involved in the development and functioning of the neural system, the PTPRM gene, which mediates cell-cell interactions and adhesion, and a region on chromosome 4 (chr4:28.7-28.9 Mb) that contained several loci affiliated with different classes of non-coding RNAs (RN7SL101P, MIR4275, MESTP3, and LINC02364). NBEA and the region on chromosome 4 were novel selection targets that were identified for the first time in Western Siberian populations. Cross-population comparisons of EHH profiles suggested a particular role for the chr4:28.7-28.9 Mb region in the local adaptation of Western Siberians. The strongest selection signal identified in Siberian sequenced genomes was formed by six SNPs on chromosome 11 (chr11:124.9-125.2 Mb). This region included well-known genes SLC37A2 and PKNOX2. SLC37A2 is most-highly expressed in the gut. Its expression is regulated by vitamin D, which is often deficient in northern regions. The PKNOX2 gene is a transcription factor of the homeobox family that is expressed in the brain and many other tissues. This gene is associated with alcohol addiction, which is widespread in many Northern Eurasian populations.

Project description:Comparative genomics studies investigating the signals of positive selection among groups of closely related species are still rare and limited in taxonomic breadth. Such studies show great promise in advancing our knowledge about the proportion and the identity of genes experiencing diversifying selection. However, methodological challenges have led to high levels of false positives in past studies. Here, we use the well-annotated genome of the purple sea urchin, Strongylocentrotus purpuratus, as a reference to investigate the signals of positive selection at 6520 single-copy orthologs from nine sea urchin species belonging to the family Strongylocentrotidae paying careful attention to minimizing false positives.We identified 1008 (15.5%) candidate positive selection genes (PSGs). Tests for positive selection along the nine terminal branches of the phylogeny identified 824 genes that showed lineage-specific adaptive diversification (1.67% of branch-sites tests performed). Positively selected codons were not enriched at exon borders or near regions containing missing data, suggesting a limited contribution of false positives caused by alignment or annotation errors. Alignments were validated at 10 loci with re-sequencing using Sanger methods. No differences were observed in the rates of synonymous substitution (d S), GC content, and codon bias between the candidate PSGs and those not showing positive selection. However, the candidate PSGs had 68% higher rates of nonsynonymous substitution (d N) and 33% lower levels of heterozygosity, consistent with selective sweeps and opposite to that expected by a relaxation of selective constraint. Although positive selection was identified at reproductive proteins and innate immunity genes, the strongest signals of adaptive diversification were observed at extracellular matrix proteins, cell adhesion molecules, membrane receptors, and ion channels. Many candidate PSGs have been widely implicated as targets of pathogen binding, inactivation, mimicry, or exploitation in other groups (notably mammals).Our study confirmed the widespread action of positive selection across sea urchin genomes and allowed us to reject the possibility that annotation and alignment errors (including paralogs) were responsible for creating false signals of adaptive molecular divergence. The candidate PSGs identified in our study represent promising targets for future research into the selective agents responsible for their adaptive diversification and their contribution to speciation.

Dataset Information

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.

Publications

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets