Genetic purging is the reduction of the frequency of a deleterious
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
, caused by an increased efficiency of natural selection prompted by
inbreeding
Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and o ...
.
Purging occurs because many deleterious alleles only express all their harmful effect when
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
, present in two copies. During inbreeding, as related individuals mate, they produce offspring that are more likely to be homozygous. Deleterious alleles appear more often, making individuals less fit genetically, i.e. they pass fewer copies of their genes to future generations. Put another way,
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charle ...
removes inbreeding children and their offspring with deleterious alleles from the
gene pool
The gene pool is the set of all genes, or genetic information, in any population, usually of a particular species.
Description
A large gene pool indicates extensive genetic diversity, which is associated with robust populations that can surv ...
, purging the deleterious alleles.
Purging reduces both the overall number of recessive deleterious alleles and the decline of mean fitness caused by inbreeding (the
inbreeding depression
Inbreeding depression is the reduced biological fitness which has the potential to result from inbreeding (the breeding of related individuals). Biological fitness refers to an organism's ability to survive and perpetuate its genetic material. In ...
for fitness).
The term "purge" is sometimes used for selection against deleterious alleles in a general way. It would avoid ambiguity to use "
purifying selection
In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilising selection through the purging of deleterious genetic polymorphisms that arise through rando ...
" in that general context, and to reserve purging to its more strict meaning defined above.
The mechanism
Deleterious alleles segregating in populations of
diploid
Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...
organisms have a remarkable trend to be, at least, partially recessive. This means that, when they occur in homozygosis (double copies), they reduce
fitness by more than twice than when they occur in heterozygosis (single copy). In other words, part of their potential deleterious effect is hidden in heterozygosis but expressed in homozygosis, so that selection is more efficient against them when they occur in homozygosis. Since inbreeding increases the probability of being homozygous, it increases the fraction of the potential deleterious effect that is expressed and, therefore, exposed to selection. This causes some increase in the selective pressure against (partially) recessive deleterious alleles, which is known as purging. Of course, it also causes some reduction in fitness, which is known as
inbreeding depression
Inbreeding depression is the reduced biological fitness which has the potential to result from inbreeding (the breeding of related individuals). Biological fitness refers to an organism's ability to survive and perpetuate its genetic material. In ...
.
Purging can reduce the average frequency of deleterious alleles across the genome below the value expected in a non-inbred population. Although this reduction usually does not compensate for all the negative effects of inbreeding, it has several beneficial consequences for fitness. A consequence is the reduction of the so-called inbreeding load. This means that, after purging, further inbreeding is expected to be less harmful. But the most immediate consequence is the reduction of the actual inbreeding depression of fitness: due to purging, mean fitness declines less than would be expected just from inbreeding and, after some initial decline, it can even rebound up to almost its value before inbreeding.
The joint effect of inbreeding and purging on fitness
Accounting for purging when predicting inbreeding depression is important in evolutionary genetics, because the fitness decline caused by inbreeding can be determinant in the evolution of
diploidy
Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...
, sexual reproduction and other main biological features. It is also important in animal breeding and, of course, in
conservation genetics
Conservation genetics is an interdisciplinary subfield of population genetics that aims to understand the dynamics of genes in populations principally to avoid extinction. Therefore, it applies genetic methods to the conservation and restoration ...
, because inbreeding depression may be a relevant factor determining the extinction risk of endangered populations, and because conservation programs can allow some breeding handling in order to control inbreeding.
In brief: due to purging, inbreeding depression is not proportional to the standard measure of inbreeding (Wright's inbreeding coefficient ), since this measure only applies to
neutral
Neutral or neutrality may refer to:
Mathematics and natural science Biology
* Neutral organisms, in ecology, those that obey the unified neutral theory of biodiversity
Chemistry and physics
* Neutralization (chemistry), a chemical reaction in ...
alleles. Instead, fitness decline is proportional to "purged inbreeding" , which gives the probability of being homozygous for deleterious alleles due to inbreeding, taking into account how they are being purged.
Purging reduces inbreeding depression in two ways: first, it slows its progress; second, it reduces the overall inbreeding depression expected in the long term. The slower the progress of inbreeding, the more efficient is purging.
A more detailed explanation
In the absence of natural selection, mean fitness would be expected to decline exponentially as inbreeding increases, where inbreeding is measured using Wright's inbreeding coefficient
(the reason why decline is exponential on instead of linear is just that fitness is usually considered a multiplicative trait). The rate at which fitness declines as increases (the inbreeding depression rate ''δ'') depends on the frequencies and deleterious effects of the alleles present in the population before inbreeding.
The above coefficient is the standard measure of inbreeding, and gives the probability that, at any given neutral locus, an individual has inherited two copies of a same gene of a common ancestor (i.e. the probability of being homozygous "by descent"). In simple conditions, can be easily computed in terms of population size or of genealogical information. is often denoted using lowercase (), but should not be confused with the coancestry coefficient.
However, the above prediction for the fitness decline rarely applies, since it was derived assuming no selection, and fitness is precisely the target trait of
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charle ...
. Thus, Wright's inbreeding coefficient for neutral loci does not apply to deleterious alleles, unless inbreeding increases so fast that the change in gene frequency is governed just by random sampling (i.e., by
genetic drift
Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.
Genetic drift may cause gene variants to disappear completely and there ...
).
Therefore, the decline of fitness should be predicted using, instead of the standard inbreeding coefficient , a "purged inbreeding coefficient" () that gives the probability of being homozygous by descent for (partially) recessive deleterious alleles, taking into account how their frequency is reduced by purging.
[ Due to purging, fitness declines at the same rate than in the absence of selection, but as a function of instead of .
This purged inbreeding coefficient can also be computed, to a good approximation, using simple expressions in terms of the population size or of the genealogy of individuals (see BOX 1). However this requires some information on the magnitude of the deleterious effects that are hidden in the heterozygous condition but become expressed in homozygosis. The larger this magnitude, denoted purging coefficient ''d'', the more efficient is purging.
An interesting property of purging is that, during inbreeding, while increases approaching a final value , can approach a much smaller final value. Hence, it is not just that purging slows the fitness decline, but also that it reduces the overall fitness loss produced by inbreeding in the long term. This is illustrated in BOX 2 for the extreme case of inbreeding depression caused by recessive lethals, which are alleles that cause death before reproduction but only when they occur in homozygosis. Purging is less effective against mildly deleterious alleles than against lethal ones but, in general, the slower is the increase of inbreeding , the smaller becomes the final value of the purged inbreeding coefficient and, therefore, the final reduction in fitness. This implies that, if inbreeding progresses slowly enough, no relevant inbreeding depression is expected in the long term. This results in the fitness of a small population, that has been a small population for a long time, can be the same as a large population with more genetic diversity. In conservation genetics, it would be very useful to ascertain the maximum rate of increase of inbreeding that allows for such efficient purging.
]
Examples
Predictive equations when inbreeding is due to small population size
Consider a large non-inbred population with mean fitness . Then, the size of the population reduces to a new smaller value (in fact, the effective population size
The effective population size (''N'e'') is a number that, in some simplified scenarios, corresponds to the number of breeding individuals in the population. More generally, ''N'e'' is the number of individuals that an idealised population wo ...
should be used here), leading to a progressive increase of inbreeding.
Then inbreeding depression occurs at a rate , due to (partially) recessive deleterious alleles that were present at low frequencies at different loci. This means that, in the absence of selection, the expected value for mean fitness after generations of inbreeding, would be:
where is the population mean for Wright's inbreeding coefficient after generations of inbreeding.
However, since selection operates upon fitness, mean fitness should be predicted taking into account both inbreeding and purging, as
In the above equation, is the average "purged inbreeding coefficient" after generations of inbreeding. It depends upon the "purging coefficient" , which represents the deleterious effects that are hidden in heterozygosis but exposed in homozygosis.
The average "purged inbreeding coefficient" can be approximated using the recurrent expression