A Map of Recent Positive Selection in the Human Genome

Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
PLoS Biology (Impact Factor: 11.77). 04/2006; 4(3):e72. DOI: 10.1371/journal.pbio.0040072
Source: PubMed

ABSTRACT The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

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    ABSTRACT: Background A number of methods are available to scan a genome for selection signatures by evaluating patterns of diversity within and between breeds. Among these, “extended haplotype homozygosity” (EHH) is a reliable approach to detect genome regions under recent selective pressure. The objective of this study was to use this approach to identify regions that are under recent positive selection and shared by the most representative Italian dairy and beef cattle breeds. Results A total of 3220 animals from Italian Holstein (2179), Italian Brown (775), Simmental (493), Marchigiana (485) and Piedmontese (379) breeds were genotyped with the Illumina BovineSNP50 BeadChip v.1. After standard quality control procedures, genotypes were phased and core haplotypes were identified. The decay of linkage disequilibrium (LD) for each core haplotype was assessed by measuring the EHH. Since accurate estimates of local recombination rates were not available, relative EHH (rEHH) was calculated for each core haplotype. Genomic regions that carry frequent core haplotypes and with significant rEHH values were considered as candidates for recent positive selection. Candidate regions were aligned across to identify signals shared by dairy or beef cattle breeds. Overall, 82 and 87 common regions were detected among dairy and beef cattle breeds, respectively. Bioinformatic analysis identified 244 and 232 genes in these common genomic regions. Gene annotation and pathway analysis showed that these genes are involved in molecular functions that are biologically related to milk or meat production. Conclusions Our results suggest that a multi-breed approach can lead to the identification of genomic signatures in breeds of cattle that are selected for the same production goal and thus to the localisation of genomic regions of interest in dairy and beef production.
    Genetics Selection Evolution 04/2015; 47:25. DOI:10.1186/s12711-015-0113-9 · 3.75 Impact Factor
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    ABSTRACT: Adaptation can be described as an evolutionary process that leads to an adjustment of the phenotypes of a population to their environment. In the classical view, new mutations can introduce novel phenotypic features into a population that leave footprints in the genome after fixation, such as selective sweeps. Alternatively, existing genetic variants may become beneficial after an environmental change and increase in frequency. Although they may not reach fixation, they may cause a shift of the optimum of a phenotypic trait controlled by multiple loci. With the availability of polymorphism data from various organisms, including humans and chimpanzees, it has become possible to detect molecular evidence of adaptation and to estimate the strength and target of positive selection. In this review, we discuss the two competing models of adaptation and suitable approaches for detecting the footprints of positive selection on the molecular level.
    01/2015; 6:5. DOI:10.1186/s13323-015-0023-1
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    ABSTRACT: Genes involved in testicular differentiation, spermatogenesis, proliferation and apoptosis of germ cells have been shown to evolve rapidly and display rapid DNA changes. These genes are therefore good candidates for explaining impairments in spermatogenesis. Initial studies of some of these genes appear to confirm this hypothesis. The RHOXF2 candidate gene belongs to the RHOX family clustered in Xq24 and is specifically expressed in the testis. It contains four exons and codes for a 288 amino acid (aa) transcription factor. It has a high degree of homology (>99.9%) with its paralogue RHOXF2B, which is also preferentially expressed in the testis. To sequence RHOXF2 and RHOXF2B in intracytoplasmic sperm injection (ICSI) patients and identify any single-nucleotide polymorphisms (SNPs) associated with impaired spermatogenesis. A cohort of 327 patients in ICSI programmes at Poissy and Bichat hospitals. All patients gave their written, informed consent to participation. One hundred patients had unaffected spermatogenesis and 227 displayed impaired spermatogenesis. The four exons in each of RHOXF2 and RHOXF2B were sequenced in 47 patients with oligospermia or non-obstructive azoospermia. Given that exons 2 and 3 were found to harbour most of the SNPs, only these two exons were sequenced in the remaining 280 subjects. Due to the extremely high degree of sequence identity between RHOXF2 and RHOXF2B, we were not able to distinguish between the sequences of these two genes. Although 9 SNPs were identified, there were no significant frequency differences between ICSI patients with normal vs. impaired spermatogenesis. Two insertions were identified: a 21-nucleotide insertion was retrieved in both groups and a guanine insertion (inducing a premature stop codon) only found in two patients with impaired spermatogenesis. RHOXF2 is a good candidate for rapid evolution by positive selection. Analysis of the polymorphism frequency in exons 2 and 3 did not allow us to correlate the identified SNPs with male infertility. However, a single nucleotide insertion was identified only in men with impaired spermatogenesis. Further work will be needed to establish whether genetic changes in RHOXF2 can give rise to defects in spermatogenesis.
    Andrologie 02/2014; 24:3. DOI:10.1186/2051-4190-24-3

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