Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

On estimating evolutionary probabilities of population variants

Ravi Patel, Sudhir Kumar
doi: https://doi.org/10.1101/475475
Ravi Patel
1Institute for Genomics and Evolutionary Medicine, Temple University
2Department of Biology, Temple University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sudhir Kumar
1Institute for Genomics and Evolutionary Medicine, Temple University
2Department of Biology, Temple University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: s.kumar@temple.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background The evolutionary probability (EP) of an allele in a DNA or protein sequence predicts evolutionarily permissible (ePerm; EP ≥ 0.05) and forbidden (eForb; EP < 0.05) variants. EP of an allele represents an independent evolutionary expectation of observing an allele in a population based solely on the long-term substitution patterns captured in a multiple sequence alignment. In the neutral theory, EP and population frequencies can be compared to identify neutral and non-neutral alleles. This approach has been used to discover candidate adaptive polymorphisms in humans, which are eForbs segregating with high frequencies. The original method to compute EP requires the evolutionary relationships and divergence times of species in the sequence alignment (a timetree), which are not known with certainty for most datasets. This requirement impedes a general use of the original EP formulation. Here, we present an approach in which the phylogeny and times are inferred from the sequence alignment itself prior to the EP calculation. We evaluate if the modified EP approach produces results that are similar to those from the original method.

Results We compared EP estimates from the original and the modified approaches by using more than 18,000 protein sequence alignments containing orthologous sequences from 46 vertebrate species. For the original EP calculations, we used species relationships from UCSC and divergence times from TimeTree web resource, and the resulting EP estimates were considered to be the ground truth. We found that the modified approaches produced reasonable EP estimates for HGMD disease missense variant and 1000 Genomes Project missense variant datasets. Our results showed that reliable estimates of EP can be obtained without a priori knowledge of the sequence phylogeny and divergence times. We also found that, in order to obtain robust EP estimates, it is important to assemble a dataset with many sequences, sampling from a diversity of species groups.

Conclusion We conclude that the modified EP approach will be generally applicable for alignments and enable the detection of potentially neutral, deleterious, and adaptive alleles in populations.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted January 30, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
On estimating evolutionary probabilities of population variants
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
On estimating evolutionary probabilities of population variants
Ravi Patel, Sudhir Kumar
bioRxiv 475475; doi: https://doi.org/10.1101/475475
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
On estimating evolutionary probabilities of population variants
Ravi Patel, Sudhir Kumar
bioRxiv 475475; doi: https://doi.org/10.1101/475475

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Evolutionary Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3686)
  • Biochemistry (7774)
  • Bioengineering (5668)
  • Bioinformatics (21245)
  • Biophysics (10563)
  • Cancer Biology (8162)
  • Cell Biology (11915)
  • Clinical Trials (138)
  • Developmental Biology (6738)
  • Ecology (10388)
  • Epidemiology (2065)
  • Evolutionary Biology (13843)
  • Genetics (9694)
  • Genomics (13056)
  • Immunology (8123)
  • Microbiology (19956)
  • Molecular Biology (7833)
  • Neuroscience (42973)
  • Paleontology (318)
  • Pathology (1276)
  • Pharmacology and Toxicology (2256)
  • Physiology (3350)
  • Plant Biology (7208)
  • Scientific Communication and Education (1309)
  • Synthetic Biology (1999)
  • Systems Biology (5528)
  • Zoology (1126)