many deleterious mutations may then be harmless , because even if one gene suffers a mutation , the redundant gene copy can provide a back - up function .
put differently , after gene duplication - which can arise through polyploidization ( whole - genome duplication ) , non - homologous recombination , or through the action of retrotransposons - one or both duplicates should experience relaxed selective constraints that result in elevated rates of evolution .
this hypothesis originated as least as early as ohno 's seminal book , which emphasized the importance of gene duplications in organismal evolution .
but for decades any test of the hypothesis had to rely on small numbers of gene duplicates ; doubts thus remained over whether conclusions derived from such case studies were representative of all genes in a genome .
such sequence information can address not only this question but also many others related to the influence of selection on gene families .
for instance , does one duplicate evolve faster and thus acquire new functions more rapidly than the other ?
? and how frequent is gene conversion of duplicate genes , in which recombination and dna repair between very similar genes convert the sequence of one to that of the other ?
to address such questions , one can use nucleotide alignments of duplicates to calculate two key parameters of molecular evolution : the fractions per nucleotide site , first , of synonymous ( silent ) nucleotide substitutions , and ks , second , of non - synonymous nucleotide substitutions ( which change the encoded amino acid ) , ka ( see box 1 ) . the ratio ka / ks provides a measure of the selection pressure to which a gene pair is subject .
if a duplicate gene pair shows a ka / ks ratio of about 1 , that is , if amino - acid replacement substitutions occur at the same rate as synonymous substitutions , then few or no amino - acid replacement substitutions have been eliminated since the gene duplication . in other words ,
the gene pair is said to be under ' purifying selection ' if ka / ks <
1 : some replacement substitutions have been purged by natural selection , presumably because of their deleterious ratio is , the greater the effects .
the smaller the ka / ks number of eliminated substitutions and the greater the selective constraint under which the two genes have evolved .
the converse case , ka / ks > 1 , indicates that replacement substitutions occur at a rate higher than expected by chance alone , so advantageous mutations have occurred in the evolution of the two duplicates .
two recent studies   analyzed these ratios in multiple fully sequenced and several partially sequenced genomes .
even very closely related gene duplicates , no older than a few million years , experience selective constraints - the ratio ka / ks is smaller than one even in these cases .
recent duplicates appear to tolerate more replacement amino - acid substitutions than older duplicates , however . for duplicates that differ at less than 5% of synonymous sites , between one in two and one in three substitutions are amino - acid replacement substitutions . for old duplicates
, this number falls to between one in ten and one in twenty replacement substitutions .
even a fine - grained statistical model that allows for differences in ka / ks among young and old duplicates may explain only 50% of the variance in evolutionary rates .
in addition , there may be species - specific differences in ka / ks , but detection of such differences is sensitive to how information on gene duplicates is extracted from genomes and on how ka and ks are estimated .
for example , one of the above studies   suggests that recent mammalian duplicates ( ka / ks = 0.45 for genes with ks between 0.05 and 0.5 ) appear to be under lower selective constraints than recent duplicates of drosophila melanogaster , caenorhabditis elegans , or arabidopsis thaliana , where ka / ks < 0.3 , whereas the other study   suggests no such differences . to determine whether one duplicate evolves faster than the other , one can compare the sequences of both duplicates with that of a related but distant ' outgroup ' gene and determine whether one duplicate has diverged to a greater extent than the other .
for example , in bacteria and mammals fewer than 10% of duplicates seem to evolve at different rates .
in contrast , a recent study focusing on ancient zebrafish duplicates - most of them developmental genes - found that about 50% of duplicates differ in their rates of evolution . despite such differences ,
these results show that it is not generally the case that one duplicate ' holds down the fort ' , and retains the original function while the other can evolve freely .
tandemly duplicated genes are known to be subject to gene conversion events that homogenize their sequences . if rampant , gene conversion could substantially distort inferences of selection pressures after gene duplication .
one group of genes with extremely slow rates of evolution , the histone h3 genes , has received recent attention in this regard . with only three amino - acid differences between animal and plant histone h3 proteins , for example ,
if so , one would expect that values of ks between histone gene duplicates would be small - reflecting recent gene conversion - and not dramatically greater than values of ka . but in organisms ranging from fungi to mammals , ka and ks differ by as much as a factor of 60 between non - tandemly clustered histone h3 genes , so evolution by gene conversion is unlikely to be frequent in this family .
another study   asked whether yeast ( saccharomyces cerevisiae ) gene duplicates show evidence of gene conversion .
part of the assay in this study was based on the observation that measures of codon - usage bias are strongly correlated with the rate of synonymous divergence of yeast genes ( because mutations in a highly expressed gene to a synonymous codon for which the respective transfer rna is rare are deleterious ) .
only 4 out of 160 yeast duplicates had a synonymous divergence ( ks ) less than expected on the basis of their codon - usage bias , showing that gene conversion is rare . in summary , although gene conversion is potentially rampant for some genes , it is most likely to be rare for the vast majority of genes
. perhaps the most difficult questions about the influence of selection after gene duplication is how frequently beneficial mutations occur .
large amounts of genome sequence information lend themselves to the establishment of databases that document the gene families that have elevated ka / ksratios .
mere sequence analysis will probably have a limited impact on answering this question , however , because finding genes with ka / ks > 1 is usually not quite enough to make a case for positive selection .
although a particular genome may contain many duplicates with ka / ks apparently above one , the observed difference from unity often does not withstand statistical scrutiny .
it does not , because positively selected amino - acid substitutions often occur only in a small region of the coding region , too small to be detectable by an elevated ka / ks ratio .
and several case studies suggest the existence of positive selection for individual gene families , including the opsin visual pigments , primate ribonuclease genes , and triosephosphate isomerases .
these studies also show that a strong case for positive selection generally requires integration of information on gene divergence , phylogeny , and protein structure and function . in summary ,
genome - scale surveys of gene duplication have the great merit of answering questions about molecular evolution without lingering doubts of statistical bias caused by small samples .
they can assess to what extent selection is relaxed after gene duplication , to what extent gene duplicates diverge at different rates , and how abundant gene conversion events are . but their biggest strength - providing summary information about thousands of gene pairs - is also their biggest weakness .
some questions , such as the abundance of beneficial mutations , generally require more information than a crude view of the whole genome can provide .
genome - scale surveys thus draw our attention to their own limitations , which call for an integration of a variety of approaches to understand genome evolution .
 immediately after a gene duplication event , the duplicate genes have redundant functions . 
 is natural selection therefore completely relaxed after duplication ? 
 does one gene evolve more rapidly than the other ? 
 several recent genome - wide studies have suggested that duplicate genes are always under purifying selection and do not always evolve at the same rate . 
None
Purifying or completely relaxed selection?
Gene conversion
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