English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Large scale variation in the rate of germ-line de novo mutation, base composition, divergence and diversity in humans

Smith, T. C. A., Arndt, P. F., & Eyre-Walker, A. (2018). Large scale variation in the rate of germ-line de novo mutation, base composition, divergence and diversity in humans. PLoS Genetics, 14(3): e1007254. doi:10.1371/journal.pgen.1007254.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0003-5529-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-552A-F
Genre: Journal Article

Files

show Files
hide Files
:
Smith.pdf (Publisher version), 3MB
Name:
Smith.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2018 Smith et al

Locators

show

Creators

show
hide
 Creators:
Smith, Thomas C. A. 1, Author
Arndt, Peter F.2, Author              
Eyre-Walker, Adam 1, Author
Affiliations:
1School of Life Sciences, University of Sussex, Brighton, United Kingdom, ou_persistent22              
2Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479638              

Content

show
hide
Free keywords: -
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2018-02-132018-03-28
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1371/journal.pgen.1007254
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS Genetics
  Other : PLoS Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 14 (3) Sequence Number: e1007254 Start / End Page: - Identifier: ISSN: 1553-7390
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000017180