Natural Selection and the Distribution of Identity-by-Descent in the Human Genome

By Albrechtsen, Anders; Moltke, Ida et al. | Genetics, September 2010 | Go to article overview

Natural Selection and the Distribution of Identity-by-Descent in the Human Genome


Albrechtsen, Anders, Moltke, Ida, Nielsen, Rasmus, Genetics


ABSTRACT

There has recently been considerable interest in detecting natural selection in the human genome. Selection will usually tend to increase identity-by-descent (IBD) among individuals in a population, and many methods for detecting recent and ongoing positive selection indirectly take advantage of this. In this article we show that excess IBD sharing is a general property of natural selection and we show that this fact makes it possible to detect several types of selection including a type that is otherwise difficult to detect: selection acting on standing genetic variation. Motivated by this, we use a recently developed method for identifying IBD sharing among individuals from genome-wide data to scan populations from the new HapMap phase 3 project for regions with excess IBD sharing in order to identify regions in the human genome that have been under strong, very recent selection. The HLA region is by far the region showing the most extreme signal, suggesting that much of the strong recent selection acting on the human genome has been immune related and acting on HLA loci. As equilibrium overdominance does not tend to increase IBD, we argue that this type of selection cannot explain our observations.

(ProQuest: ... denotes formulae omitted.)

IN recent years there has been considerable interest in detecting natural selection in humans (Bustamante et al. 2005; Nielsen et al. 2005; Voight et al. 2006; Sabeti et al. 2007; Nielsen et al. 2009; Pickrell et al. 2009). Many of the existing methods for detecting ongoing selection on a new allele have focused on haplotype homozygosity (Sabeti et al. 2002; Voight et al. 2006; Zhang et al. 2006; Sabeti et al. 2007), for instance, integrated haplotype score (iHS). The reasoning behind this is that as a favored allele increases in frequency, the region in which the mutation occurs will increase in homozygosity and experience less intra-allelic recombination at the population level. Positively selected alleles increasing in frequency will, therefore, tend to be located on haplotypes that are unexpectedly long, given their frequency in the population. Alleles on different homologous chromosomes are identical-by-descent (IBD) if they are direct copies of the same ancestral allele. Methods for detecting selection on the basis of haplotype homozygosity are, therefore, fundamentally identifying regions where a subset of the individuals share IBD haplotypes that are longer than would be expected under neutrality. Hence, detecting selection using haplotype homozygosity can be viewed as a special case of using excess IBD sharing to detect selection.

Recently several authors (Purcell et al. 2007;Thompson 2008; Albrechtsen et al. 2009; Gusev et al. 2009) have developed methods that are able to infer IBD tracts shared between pairs of individuals from outbred populations without any pedigree information, using dense genotype data such as SNP chip data. The original purpose of these methods was to identify regions of the genome-harboring disease loci with more IBD sharing among affected individuals than unaffected individuals. However, these methods can also be used to study the genetic history of the populations. As we show, they provide a new approach for detecting very recent, strong selection in the genome; and not only selection acting on a new allele, but also selection acting on standing variation, i.e., selection on alleles that were already segregating in the population when the selective advantage was introduced. This is true because natural selection in general will increase the amount of IBD sharing in a population in the area surrounding the allele under selection.

Most population genetic studies have focused on selection acting on a new allele, but it has recently been suggested that selection on standing variation is a biologically relevant model for selection as well (Orr and Betancourt 2001; Innan and Kim 2004; Hermisson and Pennings 2005; Przeworski et al.

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Natural Selection and the Distribution of Identity-by-Descent in the Human Genome
Settings

Settings

Typeface
Text size Smaller Larger
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

Cited passage

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited passage

Welcome to the new Questia Reader

The Questia Reader has been updated to provide you with an even better online reading experience.  It is now 100% Responsive, which means you can read our books and articles on any sized device you wish.  All of your favorite tools like notes, highlights, and citations are still here, but the way you select text has been updated to be easier to use, especially on touchscreen devices.  Here's how:

1. Click or tap the first word you want to select.
2. Click or tap the last word you want to select.

OK, got it!

Thanks for trying Questia!

Please continue trying out our research tools, but please note, full functionality is available only to our active members.

Your work will be lost once you leave this Web page.

For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

Already a member? Log in now.