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"Selection (Genetics)"
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The selfish gene
Dawkins articulates a gene's eye view of evolution--a view giving center stage to these persistent units of information, and in which organisms can be seen as vehicles for their replication. This work not only brought the insights of Neo-Darwinism to a wide audience, but galvanized the biology community, generating much debate and stimulating new areas of research. Forty years later, its insights remain as relevant today as on the day it was published.
Book
A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response
Fine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large (
n
= 21,546) HLA reference panel spanning five global populations based on whole-genome sequences. Despite population-specific long-range haplotypes, we demonstrated accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT) populations). Applying HLA imputation to genome-wide association study data for HIV-1 viral load in three populations (EUR, AA and LAT), we obviated effects of previously reported associations from population-specific HIV studies and discovered a novel association at position 156 in HLA-B. We pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide-binding groove, explaining 12.9% of trait variance.
A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of
HLA
alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.
Journal Article
Climbing Mount Improbable
Arguing that the perfection of the human body is the result of improbable mutation, a prominent Darwinian uses the metaphor of climbing a mountain to illustrate how natural perfection is due to the unending journey of DNA through time.
Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage
The International Stem Cell Initiative compares 125 ethnically diverse human embryonic stem cell lines at early and late passage. Data on karotype, single-nucleotide polymorphisms and methylation shed light on how the cells adapt to long-term culture.
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells,
ID1
,
BCL2L1 and HM13
, occurred in >20% of the lines. Of these genes,
BCL2L1
is a strong candidate for driving culture adaptation of ES cells.
Journal Article
Dense sampling of bird diversity increases power of comparative genomics
Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1–4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families—including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confdently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specifc variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will ofer new perspectives on evolutionary processes in cross-species comparative analyses and assist in eforts to conserve species.
Journal Article
Inside the human genome : a case for non-intelligent design
How do you explain flaw in a world engineered by God? Avise extends this age-old question to the most basic aspect of humanity's physical evidence-- our genes-- and provides the evolutionary answers.
Book
Genetic Diversity and the Efficacy of Purifying Selection across Plant and Animal Species
A central question in evolutionary biology is why some species have more genetic diversity than others and a no less important question is why selection efficacy varies among species. Although these questions have started to be tackled in animals, they have not been addressed to the same extent in plants. Here, we estimated nucleotide diversity at synonymous, πS, and nonsynonymous sites, πN, and a measure of the efficacy of selection, the ratio πN/πS, in 34 animal and 28 plant species using full genome data. We then evaluated the relationship of nucleotide diversity and selection efficacy with effective population size, the distribution of fitness effect and life history traits. In animals, our data confirm that longevity and propagule size are the variables that best explain the variation in πS among species. In plants longevity also plays a major role as well as mating system. As predicted by the nearly neutral theory of molecular evolution, the log of πN/πS decreased linearly with the log of πS but the slope was weaker in plants than in animals. This appears to be due to a higher mutation rate in long lived plants, and the difference disappears when πS is rescaled by the mutation rate. Differences in the distribution of fitness effect of new mutations also contributed to variation in πN/πS among species.
Journal Article
Evolutionary dynamics of neoantigens in growing tumors
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of neoantigens in a growing cancer by constructing a mathematical model of neoantigen evolution. The model predicts that, without immune escape, tumor neoantigens are either clonal or at low frequency; hypermutated tumors can only establish after the evolution of immune escape. Moreover, the site frequency spectrum of somatic variants under negative selection appears more neutral as the strength of negative selection increases, which is consistent with classical neutral theory. These predictions are corroborated by the analysis of neoantigen frequencies and immune escape in exome and RNA sequencing data from 879 colon, stomach and endometrial cancers.
Mathematical modeling of evolutionary dynamics of neoantigens and immune escape in growing tumors shows that strong negative selection for neoantigens inhibits tumor growth but also provides a strong selective pressure for the evolution of immune escape.
Journal Article
Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans
Background
The 2’-5’ oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations; yet, strong evidence of positive selection in the OAS region is still lacking.
Results
Here we used a broad array of selection tests in concert with neutral coalescent simulations to demonstrate a signal of adaptive introgression at the OAS locus. Furthermore, we characterized the functional consequences of the Neandertal haplotype in the transcriptional regulation of OAS genes at baseline and infected conditions. We found that cells from people with the Neandertal-like haplotype express lower levels of
OAS3
upon infection, as well as distinct isoforms of
OAS1
and
OAS2
.
Conclusions
We present evidence that a Neandertal haplotype at the OAS locus was subjected to positive selection in the human population. This haplotype is significantly associated with functional consequences at the level of transcriptional regulation of innate immune responses. Notably, we suggest that the Neandertal-introgressed haplotype likely reintroduced an ancestral splice variant of
OAS1
encoding a more active protein, suggesting that adaptive introgression occurred as a means to resurrect adaptive variation that had been lost outside Africa.
Journal Article