Relaxed Purifying Selection and Possibly High Rate of Adaptation in Primate Lineage-Specific Genes

AbstractEvidence has accumulated that some genes originate directly from previously non-genic sequences, orde novo, rather than by the duplication or fusion of existing genes. However, howde novogenes emerge and eventually become functional is largely unknown. Here we perform the first study onde novogenes that uses transcriptomics data from eleven different yeast species, all grown identically in both rich media and in oxidative stress conditions. The genomes of these species are densely-packed with functional elements, leaving little room for the co-option of genomic sequences into new transcribed loci. Despite this, we find that at least 213 transcripts (~5%) have arisende novoin the past 20 million years of evolution of baker’s yeast-or approximately 10 new transcripts every million years. Nearly half of the total newly expressed sequences are generated from regions in which both DNA strands are used as templates for transcription, explaining the apparent contradiction between the limited ‘empty’ genomic space and high rate ofde novogene birth. In addition, we find that 40% of thesede novotranscripts are actively translated and that at least a fraction of the encoded proteins are likely to be under purifying selection. This study shows that even in very highly compact genomes,de novotranscripts are continuously generated and can give rise to new functional protein-coding genes.

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On the importance of skewed offspring distributions and background selection in viral population genetics

10.1101/048975 ◽

2016 ◽

Cited By ~ 2

Author(s):

Kristen K. Irwin ◽

Stefan Laurent ◽

Sebastian Matuszewski ◽

Séverine Vuilleumier ◽

Louise Ormond ◽

...

Keyword(s):

Population Genetic ◽

Purifying Selection ◽

High Rate ◽

Viral Population ◽

Population Genetic Study ◽

Background Selection ◽

Population Sizes ◽

Population Genetic Inference ◽

Genetic Inference ◽

Future Population

AbstractMany features of virus populations make them excellent candidates for population genetic study, including a very high rate of mutation, high levels of nucleotide diversity, exceptionally large census population sizes, and frequent positive selection. However, these attributes also mean that special care must be taken in population genetic inference. For example, highly skewed offspring distributions, frequent and severe population bottleneck events associated with infection and compartmentalization, and strong purifying selection all affect the distribution of genetic variation but are often not taken in to account. Here, we draw particular attention to multiple-merger coalescent events and background selection, discuss potential mis-inference associated with these processes, and highlight potential avenues for better incorporating them in to future population genetic analyses.

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Overlapping reading frames in closely related human papillomaviruses result in modular rates of selection within E2

Journal of General Virology ◽

10.1099/vir.0.80747-0 ◽

2005 ◽

Vol 86 (5) ◽

pp. 1307-1313 ◽

Cited By ~ 36

Author(s):

Apurva Narechania ◽

Masanori Terai ◽

Robert D. Burk

Keyword(s):

Purifying Selection ◽

Human Papillomaviruses ◽

Open Reading Frames ◽

Hinge Region ◽

High Rate ◽

Synonymous Change ◽

Overlapping Reading Frames ◽

L1 And L2 ◽

Reading Frames ◽

Selection Of

A core group of four open reading frames (ORFs) is present in all known papillomaviruses (PVs): the E1 and E2 replication/transcription proteins and the L1 and L2 structural proteins. Because they are involved in processes that are essential to PV propagation, the sequences of these proteins are well-conserved. However, sequencing of novel subtypes for human papillomaviruses (HPV) 54 (AE9) and 82 (AE2/IS39), coupled to analysis of four other closely related genital HPV pairs, indicated that E2 has a higher dN/dS ratio than E1, L1 or L2. The elevated ratio is not homogeneous across the length of the ORF, but instead varies with respect to E2's three domains. The E2 hinge region is of particular interest, because its hypervariability (dN/dS>1) differs markedly from the two domains that it joins: the transcription-activation domain and the DNA-binding domain. Deciphering whether the hinge region's high rate of non-synonymous change is the result of positive Darwinian selection or relaxed constraint depends on the evolutionary behaviour of E4, an ORF that overlaps E2. The E2 hinge region is contained within E4 and non-synonymous changes in the hinge are associated with a disproportionate amount of synonymous change in E4, a case of simultaneous positive and purifying selection in overlapping reading frames. Modular rates of selection among E2 domains are a likely consequence of the presence of an embedded E4. E4 appears to be positioned in a part of the HPV genome that can tolerate non-synonymous change and purifying selection of E4 may be indicative of its functional importance.

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Estimate of the Mutation Rate per Nucleotide in Humans

Genetics ◽

10.1093/genetics/156.1.297 ◽

2000 ◽

Vol 156 (1) ◽

pp. 297-304 ◽

Cited By ~ 8

Author(s):

Michael W Nachman ◽

Susan L Crowell

Keyword(s):

Mutation Rate ◽

X Chromosome ◽

Deleterious Mutation ◽

Purifying Selection ◽

High Rate ◽

Nucleotide Substitutions ◽

Cpg Dinucleotides ◽

Rates Of Evolution ◽

Processed Pseudogenes ◽

Order Of Magnitude

Abstract Many previous estimates of the mutation rate in humans have relied on screens of visible mutants. We investigated the rate and pattern of mutations at the nucleotide level by comparing pseudogenes in humans and chimpanzees to (i) provide an estimate of the average mutation rate per nucleotide, (ii) assess heterogeneity of mutation rate at different sites and for different types of mutations, (iii) test the hypothesis that the X chromosome has a lower mutation rate than autosomes, and (iv) estimate the deleterious mutation rate. Eighteen processed pseudogenes were sequenced, including 12 on autosomes and 6 on the X chromosome. The average mutation rate was estimated to be ~2.5 × 10−8 mutations per nucleotide site or 175 mutations per diploid genome per generation. Rates of mutation for both transitions and transversions at CpG dinucleotides are one order of magnitude higher than mutation rates at other sites. Single nucleotide substitutions are 10 times more frequent than length mutations. Comparison of rates of evolution for X-linked and autosomal pseudogenes suggests that the male mutation rate is 4 times the female mutation rate, but provides no evidence for a reduction in mutation rate that is specific to the X chromosome. Using conservative calculations of the proportion of the genome subject to purifying selection, we estimate that the genomic deleterious mutation rate (U) is at least 3. This high rate is difficult to reconcile with multiplicative fitness effects of individual mutations and suggests that synergistic epistasis among harmful mutations may be common.

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Patterns of Intra- and Interhost Nonsynonymous Variation Reveal Strong Purifying Selection in Dengue Virus

Journal of Virology ◽

10.1128/jvi.77.20.11296-11298.2003 ◽

2003 ◽

Vol 77 (20) ◽

pp. 11296-11298 ◽

Cited By ~ 136

Author(s):

Edward C. Holmes

Keyword(s):

Genetic Variation ◽

Dengue Virus ◽

Purifying Selection ◽

Cell Types ◽

High Rate ◽

Random Pattern ◽

Evolutionary Divergence ◽

Considerable Uncertainty ◽

Nonsynonymous Variation

ABSTRACT Considerable uncertainty surrounds the evolutionary rates of and selection pressures acting on arthropod-borne RNA viruses (arboviruses). In particular, it is unclear why arboviruses such as dengue virus show substantial genetic variation within individual humans and mosquitoes yet low long-term rates of amino acid substitution. To address this question, I compared patterns of nonsynonymous variation in populations of dengue virus sampled at different levels of evolutionary divergence. Although nonsynonymous variation was abundant in viral populations within individual humans, there was a marked reduction in the frequency of nonsynonymous mutations in interhost comparisons. Moreover, intrahost genetic variation corresponded to a random pattern of mutation, and most of the sites that exhibited nonsynonymous variation within hosts were invariant at deeper phylogenetic levels. This loss of long-term nonsynonymous variation is the signature of extensive purifying selection such that more than 90% of all nonsynonymous mutations are deleterious. Consequently, although arboviruses are able to successfully adapt to diverse cell types, they are characterized by a high rate of deleterious mutation.

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High rate of translocation-based gene birth on the Drosophila Y chromosome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1706502114 ◽

2017 ◽

Vol 114 (44) ◽

pp. 11721-11726 ◽

Cited By ~ 19

Author(s):

Ray Tobler ◽

Viola Nolte ◽

Christian Schlötterer

Keyword(s):

Y Chromosome ◽

Molecular Mechanisms ◽

Evolutionary Dynamics ◽

Purifying Selection ◽

High Rate ◽

Linked Gene ◽

The Past ◽

New Genes ◽

Gene Acquisition ◽

Next Generation Sequencing Ngs

The Y chromosome is a unique genetic environment defined by a lack of recombination and male-limited inheritance. The Drosophila Y chromosome has been gradually acquiring genes from the rest of the genome, with only seven Y-linked genes being gained over the past 63 million years (0.12 gene gains per million years). Using a next-generation sequencing (NGS)-powered genomic scan, we show that gene transfers to the Y chromosome are much more common than previously suspected: at least 25 have arisen across three Drosophila species over the past 5.4 million years (1.67 per million years for each lineage). The gene transfer rate is significantly lower in Drosophila melanogaster than in the Drosophila simulans clade, primarily due to Y-linked retrotranspositions being significantly more common in the latter. Despite all Y-linked gene transfers being evolutionarily recent (<1 million years old), only three showed evidence for purifying selection (ω ≤ 0.14). Thus, although the resulting Y-linked functional gene acquisition rate (0.25 new genes per million years) is double the longer-term estimate, the fate of most new Y-linked genes is defined by rapid degeneration and pseudogenization. Our results show that Y-linked gene traffic, and the molecular mechanisms governing these transfers, can diverge rapidly between species, revealing the Drosophila Y chromosome to be more dynamic than previously appreciated. Our analytical method provides a powerful means to identify Y-linked gene transfers and will help illuminate the evolutionary dynamics of the Y chromosome in Drosophila and other species.

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Structure of Palladium Single-Crystal Films Prepared by Flash Evaporation onto (001) NaCl Substrates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069272 ◽

1970 ◽

Vol 28 ◽

pp. 456-457

Author(s):

L. E. Murr ◽

G. Wong

Keyword(s):

Single Crystal ◽

High Vacuum ◽

Ultra High Vacuum ◽

High Rate ◽

Flash Evaporation ◽

Optimum Load ◽

Single Crystal Films ◽

Crystal Films ◽

A Current

Palladium single-crystal films have been prepared by Matthews in ultra-high vacuum by evaporation onto (001) NaCl substrates cleaved in-situ, and maintained at ∼ 350° C. Murr has also produced large-grained and single-crystal Pd films by high-rate evaporation onto (001) NaCl air-cleaved substrates at 350°C. In the present work, very large (∼ 3cm2), continuous single-crystal films of Pd have been prepared by flash evaporation onto air-cleaved (001) NaCl substrates at temperatures at or below 250°C. Evaporation rates estimated to be ≧ 2000 Å/sec, were obtained by effectively short-circuiting 1 mil tungsten evaporation boats in a self-regulating system which maintained an optimum load current of approximately 90 amperes; corresponding to a current density through the boat of ∼ 4 × 104 amperes/cm2.

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Rapid Freezing of Freeze-Etch Specimens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003275 ◽

1980 ◽

Vol 38 ◽

pp. 752-755

Author(s):

A. Elgsaeter ◽

T. Espevik ◽

G. Kopstad

Keyword(s):

Low Temperature ◽

Metal Surface ◽

Relative Velocity ◽

Thermal Contact ◽

High Rate ◽

Rapid Freezing ◽

Temperature Decrease ◽

Freeze Etching

The importance of a high rate of temperature decrease (“rapid freezing”) when freezing specimens for freeze-etching has long been recognized1. The two basic methods for achieving rapid freezing are: 1) dropping the specimen onto a metal surface at low temperature, 2) bringing the specimen instantaneously into thermal contact with a liquid at low temperature and subsequently maintaining a high relative velocity between the liquid and the specimen. Over the last couple of years the first method has received strong renewed interest, particularily as the result of a series of important studies by Heuser and coworkers 2,3. In this paper we will compare these two freezing methods theoretically and experimentally.

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