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Heterozygous organisms profit from pairs of gene alleles. Harmful alleles when being recessive can be carried without any harm for the organism. Only when two harmful recessive alleles form a gene the negative effect is produced. As described in wiki article on allele:

A number of genetic disorders are caused when an individual inherits two recessive alleles for a single-gene trait. Recessive genetic disorders include Albinism, Cystic Fibrosis, Galactosemia, Phenylketonuria (PKU), and Tay-Sachs Disease. Other disorders are also due to recessive alleles, but because the gene locus is located on the X chromosome, so that males have only one copy (that is, they are hemizygous), they are more frequent in males than in females. Examples include red-green color blindness and Fragile X syndrome.

But some illnesses are carried by dominant alleles (from the same article):

Other disorders, such as Huntington disease, occur when an individual inherits only one dominant allele.

My questions are:

  1. How does harm from alleles correlate with their recessiveness? Generally speaking, do harmful alleles tend to be more recessive?
  2. How does benefits from alleles correlate with their dominance? Generally speaking, do "beneficial" alleles tend to be more dominant?
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    $\begingroup$ Very harmful dominant alleles tend to go extinct --> harmful alleles found in a population are usually recessive. $\endgroup$ – fileunderwater May 26 '15 at 10:15
  • $\begingroup$ following up on fileunderwater's comment - dominant alleles (if complete) are exposed to selection every time they occur, recessive only when they are homozygous, which means recessive alleles with deleterious effects can persist at low frequencies easily (see Rice 1984 for a discussion related to X chromosome linkage and hemizygosity in males: jstor.org/stable/2408385?seq=1#page_scan_tab_contents) Novel deleterious mutations are not necessarily biased to being recessive as far as I know. $\endgroup$ – rg255 May 26 '15 at 10:43
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Instead of dividing mutations into two classes, dominant vs. recessive, consider categorizing them into classes based on how the mutation affects the gene--or the gene product. This yields loss-of-function (lf) alleles, that reduce the activity of the gene, or its product, and gain-of-function (gf) alleles that act as if they somehow increase the activity of the gene, or its product.

The logic underlying this classification was described in this classic reference: Muller, H. J. 1932. Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics, pp. 213–255. Since this was before DNA had been shown to be the genetic material his arguments are based solely on the phenotype of animals carrying various combinations of chromosomes. In particular he relies on genetic duplications and deficiencies (or deletions). In this nomenclature + indicates a chromosome carrying a wild-type (wt) allele of the gene, and m indicates a chromosome carrying a mutant allele of the gene. So if an +/m animal appears Wild-Type then that allele is recessive. Similarly, if an +/m animal has a Mutant phenotype then the allele is dominant.

There are two types of lf alleles:

  1. a hypomorph is a partial reduction in function and retains some residual gene function (e.g., a weak missense mutation, or a temperature-sensitive (ts) mutation. A hypomorph is recessive to a wt allele.

  2. an amorph is what we would call a true genetic and molecular null allele, a complete knockout of the gene, where there is no measurable function left (e.g., a nonsense mutation early in the protein coding region, or a small deletion that only removes a single gene). Amorphs are normally recessive to a wt allele (but see below for an exception)

There are three types of gf alleles:

  1. a hypermorph that elevates the level of the wt gene function (e.g., a promoter mutation that removes a negative regulatory site, leading to increased expression). Hypermorphs are dominant.

  2. an antimorph, or so-called dominant-negative (dn) allele that produces a mutant gene product that somehow interferes with the wt gene product (think poison product as one model). Antimorphs are always dominant over wt.

  3. a neomorph, an allele the results in a completely new gene function (e.g., if a glycolytic enzyme acquired sequence-specific DNA-binding activity, perhaps from a gene fusion event(?)). Neomorphic alleles are extremely rare and almost always dominant over wt.

So we have a straightforward mapping of lf alleles to recessive phenotypes, and gf alleles to dominant phenotypes. However there is an important exception to this simple scheme for genes that are dose-sensitive, or haploinsufficient. These are dominant lf alleles. For example, when halving the level of the gene product causes a mutant phenotype: +/null. Some well-known examples from the developmental genetics of model organisms are the Ubx gene, and the Notch gene from D. melanogaster.

Further discussion of these terms can also be found in Wikipedia

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    $\begingroup$ Can you add references to some of your claims (e.g. "Neomorphic alleles are [...] almost always dominant over wt")? $\endgroup$ – fileunderwater May 26 '15 at 12:17
  • $\begingroup$ @fileunderwater Done. As I recall, Muller did not discuss the fabled recessive neomorph as a category in his paper, and it is not clear to me if there are known examples of recessive neomorphic alleles, however my understanding is that this class remains a formal possibility. In general the literature treats all neomorphic alleles as dominant. $\endgroup$ – mdperry May 26 '15 at 17:29
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    $\begingroup$ Honestly, I think the whole concept of recessive and dominant is unhelpful when trying to understand genetics and we'd be better off teaching the concepts in this answer from the very start. $\endgroup$ – Jack Aidley Jun 10 '15 at 8:53
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Harmful alleles can be both recessive or dominant. They do not tend to be more recessive or more dominant. But, you must look at it from a population genetics point of view. When a allele is dominant, it tends to be a highly selected for trait, an analogy of this would be black eyes are a dominant trait compared to blue eyes or green eyes, which is why you see so many people with black eyes in the world than blue.

So therefore dominant alleles are highly selected than recessive ones and when a dominant trait is harmful, the subject tends to get killed off or the line is destroyed in the process by the natural course of reproduction. What remains are recessive alleles which do not get a chance to attain recessiveness and are therefore carried forward by evolution as passenger, never expressing themselves until they get the chance to attain homozygous recessive state.

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    $\begingroup$ Welcome to Biology! Could you add a reference or two please? $\endgroup$ – AliceD May 26 '15 at 11:17

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