Favorable Mutations? Help me!!

There is an obvious genetic signature of positive mutations that can be detected. The test for these positive mutations is:"The idea behind the test is that if synonymous mutations are essentially neutral because they do not result in a change in a protein, the rate of synonymous site evolution will equal the mutation rate. Nonsynonymous mutations, because they result in a change in a protein product, are more likely to be subject to natural selection. If most nonsynonymous mutations are deleterious, then the rate of nonsynonymous evolution will be lower than neutral rate. If a substantial fraction of nonsynonymous mutations are beneficial, however, the average rate of nonsynonymous evolution can be higher than the neutral rate."This has been detected in many genes, far too many to list them all so here are some of the categories of genes in which beneficial mutations have been detected (each category represents several genes and each gene several beneficial mutations):Host defence genesParasite response genesDetoxification genesDevelopmental genesGenes involves in digestionGenes involved in energy metabolismOdour receptorsPigmentation genesGenes involved in reproductionsee also the adaptive evolution database: http://www.sbc.su.se/~liberles/TAED3.0/2index.htmlA large fraction of many genomes are the result of gene duplications which have evolved to become indispensible to many organisms for example here is a list of organisms followed by the number of genes that evolved from duplicates. Of course each dupliucate represents a minimum of 1 beneficical mutation (the original duplication) and invariably several other beneficial mutations that give the duplicate distinct functions from the parent gene.Bacteria:
Mycoplasma pneumoniae 298
Helicobacter pylori 266
Haemophilus influenzae 284Archaea:
Archaeoglobus fulgidus 719Eukarya:
Saccharomyces cerevisiae 1858
Caenorhabditis elegans 8971
Drosophila melanogaster 5536
Arabidopsis thaliana 16 574
Homo sapiens 15 343So that list represents a minimum of 47,272 beneficial mutations! i hope thats enough Ford MJ. Applications of selective neutrality tests to molecular ecology. Mol Ecol. 2002 Aug;11(8):1245-62.Jianzhi Zhang. Evolution by gene duplication: an update. TRENDS in Ecology and Evolution Vol.18 No.6 June 2003

Although non random mutation is a possible explanation there has not been a single proven example of non random mutation (Hall's lac operon experiments seemed to have proved them but a better explanation has since been provided) so something that as far as we know doesn't exist seems to be less sensible explanation than random mutation that we know does exist.Another interesting example of beneficial mutations this time the number between two closely related species:"we therefore estimate that there have been approximately 270,000 positively selected amino-acid substitutions in the evolution of Drosophila simulans and D. yakuba"This of course does not include gene regulatory mutations that are responsible for the majority of heritable phenotypic variation in a species (about 60% of human variation is regulatory the rest is protein polymorhism). Regulatory differences seem to be responsible for the majority of the divergence between closely related species for examples humans and chimps where most of the proteins are virtually identical. So the number of beneficial protein changing mutations is likely to be lower than beneficial regulatory mutations.N. G. Smith and A. Eyre-Walker. Adaptive protein evolution in Drosophila. Nature 415 (6875):1022-1024, 2002.

some more interesting research on the evolution of duplicated genes:B. Papp, C. Pal and L. D. Hurst. Evolution of cis-regulatory elements in duplicated genes of yeast. TRENDS in Genetics Vol.19 No.8 August 2003."An increasing number of studies report that functional divergence in duplicated genes is accompanied by gene expression changes, although the evolutionary mechanism behind this process remains unclear. Our genomic analysis on the yeast Saccharomyces cerevisiae shows that the number of shared regulatory motifs in the duplicates decreases with evolutionary time, whereas the total number of regulatory motifs remains unchanged. Moreover, genes with numerous paralogs in the yeast genome do not have especially low number of regulatory motifs. These findings indicate that degenerative complementation is not the sole mechanism behind expression divergence in yeast. Moreover, we found some evidence for the action of positive selection on cis-regulatory motifs after gene duplication. These results suggest that the evolution of functional novelty has a substantial role in yeast duplicate gene evolution."Another example of positive mutations after gene duplication and an increase in information (new gene regulatory sequences). Not that this will stop some people from falsely asserting that both these things are impossible.

More positive mutations:Makova KD, Li WH. Genome Res. 2003 Jul;13(7):1638-45.Divergence in the spatial pattern of gene expression between human duplicate
genes."Microarray gene expression data provide a wealth of information for elucidating
the mode and tempo of molecular evolution. In the present study,we analyze the
spatial expression pattern of human duplicate gene pairs by using
oligonucleotide microarray data,and study the relationship between coding
sequence divergence and expression divergence. First,we find a strong positive
correlation between the proportion of duplicate gene pairs with divergent
expression (as presence or absence of expression in a tissue) and both
synonymous (K(S)) and nonsynonymous divergence (K(A)). The divergence of gene
expression between human duplicate genes is rapid, probably faster than that
between yeast duplicates in terms of generations. Second,we compute the
correlation coefficient (R) between the expression levels of duplicate genes in
different tissues and find a significant negative correlation between R and
K(S). There is also a negative correlation between R and K(A), when K(A)
0.2. These results indicate that protein sequence divergence and divergence of
spatial expression pattern are initially coupled. Finally,we compare the
functions of those duplicate genes that show rapid divergence in spatial
expression pattern with the functions of those duplicate genes that show no or
little divergence in spatial expression."

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Gene duplicates rapidly accumulate mutations giving the genes new functions and expression patterns giving rise to an increase in information and complexity.

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Zhang P, Gu Z, Li WH. Genome Biol. 2003;4(9):R56. Epub 2003 Sep 01.

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Different evolutionary patterns between young duplicate genes in the human
genome.

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Application Unavailable | Springer Nature

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"BACKGROUND: Following gene duplication, two duplicate genes may experience
relaxed functional constraints or acquire different mutations, and may also
diverge in function. Whether the two copies will evolve in different patterns
remains unclear, however, because previous studies have reached conflicting
conclusions. In order to resolve this issue, by providing a general picture, we
studied 250 independent pairs of young duplicate genes from the whole human
genome. RESULTS: We showed that nearly 60% of the young duplicate gene pairs
have evolved at the amino-acid level at significantly different rates from each
other. More than 25% of these gene pairs also showed significantly different
ratios of nonsynonymous to synonymous rates (Ka/Ks ratios). Moreover, duplicate
pairs with different rates of amino-acid substitution also tend to differ in the
Ka/Ks ratio, with the fast-evolving copy tending to have a slightly higher Ks
than the slow-evolving one. Lastly, a substantial portion of fast-evolving
copies have accumulated amino-acid substitutions evenly across the protein
sequences, whereas most of the slow-evolving copies exhibit uneven substitution
patterns. CONCLUSIONS: Our results suggest that duplicate genes tend to evolve
in different patterns following the duplication event. One copy evolves faster
than the other and accumulates amino-acid substitutions evenly across the
sequence, whereas the other copy evolves more slowly and accumulates amino-acid
substitutions unevenly across the sequence. Such different evolutionary patterns
may be largely due to different functional constraints on the two copies."

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Natural selection plays a role in the evolution of the new information that results from gene duplications.

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Conant GC, Wagner A. Genome Res. 2003 Sep;13(9):2052-8.

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Asymmetric sequence divergence of duplicate genes.

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http://www.santafe.edu/...tions/Working-Papers/03-06-037.pdf

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"Much like humans, gene duplicates may be created equal, but they do not stay
that way for long. For four completely sequenced genomes we show that 20%-30% of
duplicate gene pairs show asymmetric evolution in the amino acid sequence of
their protein products. That is, one of the duplicates evolves much faster than
the other. The greater this asymmetry, the greater the ratio Ka/Ks of amino acid
substitutions (Ka) to silent substitutions (Ks) in a gene pair. This indicates
that most asymmetric divergence may be caused by relaxed selective constraints
on one of the duplicates. However, we also find some candidate duplicates where
positive (directional) selection of beneficial mutations (Ka/Ks > 1) may play a
role in asymmetric divergence. Our analysis rests on a codon-based model of
molecular evolution that allows a test for asymmetric divergence in Ka. The
method is also more sensitive in detecting positive selection (Ka/Ks > 1) than
models relying only on pairwise gene comparisons."

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Li W, Schuler MA, Berenbaum MR. Proc Natl Acad Sci U S A. 2003 Sep 10 [Epub ahead of print].

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Diversification of furanocoumarin-metabolizing cytochrome P450 monooxygenases in
two papilionids: Specificity and substrate encounter rate.

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"Diversification of cytochrome P450 monooxygenases (P450s) is thought to result
from antagonistic interactions between plants and their herbivorous enemies.
However, little direct evidence demonstrates the relationship between selection
by plant toxins and adaptive changes in herbivore P450s. Here we show that the
furanocoumarin-metabolic activity of CYP6B proteins in two species of
swallowtail caterpillars is associated with the probability of encountering host
plant furanocoumarins. Catalytic activity was compared in two closely related
CYP6B4 and CYP6B17 groups in the polyphagous congeners Papilio glaucus and
Papilio canadensis. Generally, P450s from P. glaucus, which feeds occasionally
on furanocoumarin-containing host plants, display higher activities against
furanocoumarins than those from P. canadensis, which normally does not encounter
furanocoumarins. These P450s in turn catalyze a larger range of furanocoumarins
at lower efficiency than CYP6B1, a P450 from Papilio polyxenes, which feeds
exclusively on furanocoumarin-containing host plants. Reconstruction of the
ancestral CYP6B sequences using maximum likelihood predictions and comparisons
of the sequence and geometry of their active sites to those of contemporary
CYP6B proteins indicate that host plant diversity is directly related to P450
activity and inversely related to substrate specificity. These predictions
suggest that, along the lineage leading to Papilio P450s, the ancestral, highly
versatile CYP6B protein presumed to exist in a polyphagous species evolved
through time into a more efficient and specialized CYP6B1-like protein in
Papilio species with continual exposure to furanocoumarins. Further
diversification of Papilio CYP6Bs has likely involved interspersed events of
positive selection in oligophagous species and relaxation of functional
constraints in polyphagous species."

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Natural selection leads to an increase in enzyme specificity and efficiancy over time.

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Jia L, Clegg MT, Jiang T. Plant Mol Biol. 2003 Jun;52(3):627-42.

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Excess non-synonymous substitutions suggest that positive selection episodes
occurred during the evolution of DNA-binding domains in the Arabidopsis R2R3-MYB
gene family.

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"It has been suggested that evolutionary changes in regulatory genes may be the
predominant molecular mechanism governing both physiological and morphological
evolution. R2R3-AtMYB is one of the largest transcription factor gene families
in Arabidopsis. Using inferred ancestral sequences we show that several lineages
in the R2R3-AtMYB phylogeny experienced excess non-synonymous nucleotide
substitution upon gene duplication, indicating episodes of positive selection
driving adaptive shifts early in the evolution of this gene family. A noise
reduction technique was then used to determine individual sites in DNA-binding
domains (R2 domain and R3 domain) of R2R3-AtMYB protein sequence that were
favored by frequent non-synonymous substitutions. The analyses reveal that the
first helix (helix1) and the second helix (helix2) in both R2 and R3 domains are
characterized by more frequent non-synonymous substitutions, and thus
experienced significantly higher positive selection pressure than the third
helix (helix3) in both domains. Previous MYB protein structure studies have
suggested that helix1 and helix2 in both R2 and R3 domains are involved in the
characteristic packing of R2R3-AtMYB DNA-binding domains. This suggests that
excess non-synonymous substitutions in these helices could have resulted in MYB
recognition of novel gene target sites."

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Yet more natural selection for beneficial mutations leading to an increase in information after a gene duplication.

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Mol Biol Evol. 2003 Aug 29 [Epub ahead of print].

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Ceplitis H, Ellegren H. Adaptive Molecular Evolution of PKCIW, a Female-Specific Gene in Birds.

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"It is well established that many genes on the male-specific Y chromosome of
organisms such as mammals are involved in male reproduction and may evolve
rapidly due to positive selection on male reproductive traits. In contrast, very
little is known about the function and evolution of W-linked genes restricted to
the female genome of organisms with female heterogamety. For birds (males ZZ,
females ZW), only one W-linked gene (PKCIW) is sufficiently different from its
Z-linked homolog to indicate a female-specific function. Here we report that
PKCIW shows evidence of adaptive molecular evolution, implying strong positive
selection for new functional properties in female birds. Moreover, since PKCIW
is expressed in the gonads of female birds just prior to sexual differentiation,
and is thus a candidate for sex determination, it suggests adaptive evolution
related to female development. This provides the first example of Darwinian
evolution of a gene restricted to the female genome of any organism. Given that
PKCIW exists in multiple copies on W, similar to some testis-specific genes
amplified on mammalian Y, avian PKCIW may thus potentially represent a female
parallel to the organization and evolution of Y chromosome genes involved in
male reproduction and development."

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It would be fascinating to see if W linked genes under positive selection were found in the cuckoo where host specificity (egg size colour etc.) is transmitted via the female line only. Incidentaly i wonder if all the different host races of cuckoo were found on board the 'ark' (many different female cuckoos) of did they all evolve their amazing host specicficity post 'flood'.

Actually evidence of positive selection does prove the mutated type is more viable than the ancestoral genotype in the environment that it is currently in. That's the whole point of selective neutrality tests.You are right that different functional constraints do not demonstrate a positive effect, neverless there is good evidence that many genes have evolved by duplication that now play essential roles in organisms, which i would argue is a positive effect. Interestingly relaxed functional constraint is what Susumu Ohno suggested as the cause of new function evolution after gene duplication."Moreover, we found some evidence for the action of positive selection on cis-regulatory motifs after gene duplication. These results suggest that the evolution of functional novelty has a substantial role in yeast duplicate gene evolution."