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Adam Eyrewalker - One of the best experts on this subject based on the ideXlab platform.
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large Scale Variation in the rate of germ line de novo mutation base composition divergence and diversity in humans
PLOS Genetics, 2018Co-Authors: Tom Smith, Peter F Arndt, Adam EyrewalkerAbstract:It has long been suspected that the rate of mutation varies across the human genome at a large Scale based on the divergence between humans and other species. However, it is now possible to directly investigate this question using the large number of de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We investigate a number of questions pertaining to the distribution of mutations using more than 130,000 DNMs from three large datasets. We demonstrate that the amount and pattern of Variation differs between datasets at the 1MB and 100KB Scales probably as a consequence of differences in sequencing technology and processing. In particular, datasets show different patterns of correlation to genomic variables such as replication time. Never-the-less there are many commonalities between datasets, which likely represent true patterns. We show that there is Variation in the mutation rate at the 100KB, 1MB and 10MB Scale that cannot be explained by Variation at smaller Scales, however the level of this Variation is modest at large Scales–at the 1MB Scale we infer that ~90% of regions have a mutation rate within 50% of the mean. Different types of mutation show similar levels of Variation and appear to vary in concert which suggests the pattern of mutation is relatively constant across the genome. We demonstrate that Variation in the mutation rate does not generate large-Scale Variation in GC-content, and hence that mutation bias does not maintain the isochore structure of the human genome. We find that genomic features explain less than 40% of the explainable variance in the rate of DNM. As expected the rate of divergence between species is correlated to the rate of DNM. However, the correlations are weaker than expected if all the Variation in divergence was due to Variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. In contrast to divergence, we find that most of the Variation in diversity can be explained by Variation in the mutation rate. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered.
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large Scale Variation in the rate of de novo mutation base composition divergence and diversity in humans
bioRxiv, 2017Co-Authors: Thomas B Smith, Adam EyrewalkerAbstract:It has long been suspected that the rate of mutation varies across the human genome at a large Scale based on the divergence between humans and other species. It is now possible to directly investigate this question using >40,000 de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We show that there is Variation in the mutation rate at the 100KB and 1MB Scale that cannot be explained by Variation at smaller Scales, however the level of this Variation is modest. Different types of mutation show similar levels of Variation and appear to vary in concert, and in a manner such that they are not predicted to generate Variation in base composition across the genome. Regressing the rate of DNM against a range of genomic features suggests that nucleosome occupancy is the most important correlate, but that GC content, recombination rate, replication time and various histone methylation signals also correlate significantly. In total the model explains ~75% of the explainable variance suggesting that it will be useful for predicting large Scale Variation in the mutation rate. As expected the rate of divergence between species and the level of diversity within humans are correlated to the rate of DNM. However, the correlations are weaker than if all the Variation in divergence was due to Variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered. Our results have important implications for understanding large Scale Variation in base composition and the use of divergence and diversity data to study Variation in the mutation rate.
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a test of whether selection maintains isochores using sites polymorphic for alu and l1 element insertions
Genetics, 2002Co-Authors: Elise M S Belle, Adam EyrewalkerAbstract:ONE of the most striking features of the human genome is the large-Scale Variation in GC content that is found along chromosomes. This Variation was discovered in 1973 ([Filipski et al. 1973][1]) and was originally thought to be organized as a series of “isochores,” blocks of DNA of homogeneous
Simon R. Thorrold - One of the best experts on this subject based on the ideXlab platform.
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Continental-Scale Variation in otolith geochemistry of juvenile American shad (Alosa sapidissima)
Canadian Journal of Fisheries and Aquatic Sciences, 2008Co-Authors: Benjamin D. Walther, Simon R. ThorroldAbstract:We assembled a comprehensive atlas of geochemical signatures in juvenile American shad (Alosa sapidissima) to discriminate natal river origins on a large spatial Scale and at a high spatial resolution. Otoliths and (or) water samples were collected from 20 major spawning rivers from Florida to Quebec and were analyzed for elemental (Mg:Ca, Mn:Ca, Sr:Ca, and Ba:Ca) and isotope ( 87 Sr: 86 Sr and d 18 O) ratios. We examined correlations between water chemistry and otolith composition for five rivers where both were sampled. While Sr:Ca, Ba:Ca, 87 Sr: 86 Sr, and d 18 O values in otoliths reflected those ratios in ambient waters, Mg:Ca and Mn:Ca ratios in otoliths varied independently of water chemistry. Geochemical signatures were highly distinct among rivers, with an average classification accuracy of 93% using only those variables where otolith values were accurately predicted from water chemistry data. The study represents the largest assembled data- base of otolith signatures from the entire native range of a species, encompassing approximately 2700 km of coastline and 19 degrees of latitude and including all major extant spawning populations. This database will allow reliable estimates of natal origins of migrating ocean-phase American shad from the 2004 annual cohort in the future. Resume´ : Nous avons compileun vaste atlas des signatures geochimiques des jeunes aloses savoureuses (Alosa sapidis- sima) afin de pouvoir reconnaoˆtre leur riviere d'origine a la naissance sur une grande echelle geographique et aune forte resolution spatiale. Nous avons recoltedes otolithes et (ou) des echantillons d'eau dans 20 rivieres importantes pour la re- production de la Floride au Quebec et nous avons mesureles rapports des elements (Mg:Ca, Mn:Ca, Sr:Ca et Ba:Ca) et des isotopes ( 87 Sr: 86 Sr et d 18 O). Nous avons examineles correlations entre la chimie de l'eau et la composition des oto- lithes dans cinq rivieres oules deux ont eteechantillonnees. Alors que les valeurs de Sr:Ca, Ba:Ca, 87 Sr: 86 Sr et d 18 O dans les otolithes refletent les rapports mesures dans les eaux ambiantes, les rapports Mg:Ca et Mn:Ca dans les otolithes varient independamment de la chimie de l'eau. Les signatures geochimiques sont tres distinctes d'une riviere al'autre et la jus- tesse moyenne des classifications est de 93 % lorsqu'on utilise seulement les variables dont la teneur dans les otolithes peut etre predite avec precision a partir des donnees de chimie des eaux. Notre etude comprend la plus grande banque de signatures d'otolithes provenant de l'ensemble de l'aire de repartition indigene d'une espece, couvrant environ 2700 km de cotes et 19 degres de latitude et incluant toutes les principales populations reproductrices actuelles. Cette banque de don- nees permettra dans le futur des determinations fiables de la riviere d'origine ala naissance des aloses de la cohorte an- nuelle de 2004 en migration durant leur phase oceanique. (Traduit par la Redaction)
Tom Smith - One of the best experts on this subject based on the ideXlab platform.
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large Scale Variation in the rate of germ line de novo mutation base composition divergence and diversity in humans
PLOS Genetics, 2018Co-Authors: Tom Smith, Peter F Arndt, Adam EyrewalkerAbstract:It has long been suspected that the rate of mutation varies across the human genome at a large Scale based on the divergence between humans and other species. However, it is now possible to directly investigate this question using the large number of de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We investigate a number of questions pertaining to the distribution of mutations using more than 130,000 DNMs from three large datasets. We demonstrate that the amount and pattern of Variation differs between datasets at the 1MB and 100KB Scales probably as a consequence of differences in sequencing technology and processing. In particular, datasets show different patterns of correlation to genomic variables such as replication time. Never-the-less there are many commonalities between datasets, which likely represent true patterns. We show that there is Variation in the mutation rate at the 100KB, 1MB and 10MB Scale that cannot be explained by Variation at smaller Scales, however the level of this Variation is modest at large Scales–at the 1MB Scale we infer that ~90% of regions have a mutation rate within 50% of the mean. Different types of mutation show similar levels of Variation and appear to vary in concert which suggests the pattern of mutation is relatively constant across the genome. We demonstrate that Variation in the mutation rate does not generate large-Scale Variation in GC-content, and hence that mutation bias does not maintain the isochore structure of the human genome. We find that genomic features explain less than 40% of the explainable variance in the rate of DNM. As expected the rate of divergence between species is correlated to the rate of DNM. However, the correlations are weaker than expected if all the Variation in divergence was due to Variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. In contrast to divergence, we find that most of the Variation in diversity can be explained by Variation in the mutation rate. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered.
Benjamin D. Walther - One of the best experts on this subject based on the ideXlab platform.
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Continental-Scale Variation in otolith geochemistry of juvenile American shad (Alosa sapidissima)
Canadian Journal of Fisheries and Aquatic Sciences, 2008Co-Authors: Benjamin D. Walther, Simon R. ThorroldAbstract:We assembled a comprehensive atlas of geochemical signatures in juvenile American shad (Alosa sapidissima) to discriminate natal river origins on a large spatial Scale and at a high spatial resolution. Otoliths and (or) water samples were collected from 20 major spawning rivers from Florida to Quebec and were analyzed for elemental (Mg:Ca, Mn:Ca, Sr:Ca, and Ba:Ca) and isotope ( 87 Sr: 86 Sr and d 18 O) ratios. We examined correlations between water chemistry and otolith composition for five rivers where both were sampled. While Sr:Ca, Ba:Ca, 87 Sr: 86 Sr, and d 18 O values in otoliths reflected those ratios in ambient waters, Mg:Ca and Mn:Ca ratios in otoliths varied independently of water chemistry. Geochemical signatures were highly distinct among rivers, with an average classification accuracy of 93% using only those variables where otolith values were accurately predicted from water chemistry data. The study represents the largest assembled data- base of otolith signatures from the entire native range of a species, encompassing approximately 2700 km of coastline and 19 degrees of latitude and including all major extant spawning populations. This database will allow reliable estimates of natal origins of migrating ocean-phase American shad from the 2004 annual cohort in the future. Resume´ : Nous avons compileun vaste atlas des signatures geochimiques des jeunes aloses savoureuses (Alosa sapidis- sima) afin de pouvoir reconnaoˆtre leur riviere d'origine a la naissance sur une grande echelle geographique et aune forte resolution spatiale. Nous avons recoltedes otolithes et (ou) des echantillons d'eau dans 20 rivieres importantes pour la re- production de la Floride au Quebec et nous avons mesureles rapports des elements (Mg:Ca, Mn:Ca, Sr:Ca et Ba:Ca) et des isotopes ( 87 Sr: 86 Sr et d 18 O). Nous avons examineles correlations entre la chimie de l'eau et la composition des oto- lithes dans cinq rivieres oules deux ont eteechantillonnees. Alors que les valeurs de Sr:Ca, Ba:Ca, 87 Sr: 86 Sr et d 18 O dans les otolithes refletent les rapports mesures dans les eaux ambiantes, les rapports Mg:Ca et Mn:Ca dans les otolithes varient independamment de la chimie de l'eau. Les signatures geochimiques sont tres distinctes d'une riviere al'autre et la jus- tesse moyenne des classifications est de 93 % lorsqu'on utilise seulement les variables dont la teneur dans les otolithes peut etre predite avec precision a partir des donnees de chimie des eaux. Notre etude comprend la plus grande banque de signatures d'otolithes provenant de l'ensemble de l'aire de repartition indigene d'une espece, couvrant environ 2700 km de cotes et 19 degres de latitude et incluant toutes les principales populations reproductrices actuelles. Cette banque de don- nees permettra dans le futur des determinations fiables de la riviere d'origine ala naissance des aloses de la cohorte an- nuelle de 2004 en migration durant leur phase oceanique. (Traduit par la Redaction)
Peter F Arndt - One of the best experts on this subject based on the ideXlab platform.
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large Scale Variation in the rate of germ line de novo mutation base composition divergence and diversity in humans
PLOS Genetics, 2018Co-Authors: Tom Smith, Peter F Arndt, Adam EyrewalkerAbstract:It has long been suspected that the rate of mutation varies across the human genome at a large Scale based on the divergence between humans and other species. However, it is now possible to directly investigate this question using the large number of de novo mutations (DNMs) that have been discovered in humans through the sequencing of trios. We investigate a number of questions pertaining to the distribution of mutations using more than 130,000 DNMs from three large datasets. We demonstrate that the amount and pattern of Variation differs between datasets at the 1MB and 100KB Scales probably as a consequence of differences in sequencing technology and processing. In particular, datasets show different patterns of correlation to genomic variables such as replication time. Never-the-less there are many commonalities between datasets, which likely represent true patterns. We show that there is Variation in the mutation rate at the 100KB, 1MB and 10MB Scale that cannot be explained by Variation at smaller Scales, however the level of this Variation is modest at large Scales–at the 1MB Scale we infer that ~90% of regions have a mutation rate within 50% of the mean. Different types of mutation show similar levels of Variation and appear to vary in concert which suggests the pattern of mutation is relatively constant across the genome. We demonstrate that Variation in the mutation rate does not generate large-Scale Variation in GC-content, and hence that mutation bias does not maintain the isochore structure of the human genome. We find that genomic features explain less than 40% of the explainable variance in the rate of DNM. As expected the rate of divergence between species is correlated to the rate of DNM. However, the correlations are weaker than expected if all the Variation in divergence was due to Variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. In contrast to divergence, we find that most of the Variation in diversity can be explained by Variation in the mutation rate. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered.
