Hybrizyme

Originally hybrizymes were defined as "unexpected allelic electromorphs associated with hybrid zones", a formal term proposed by renowned conservation geneticist and biogeographer David S. Woodruff in 1988.^[1] By suggesting a new definition for a phenomenon that had been previously widely observed Woodruff's interpretation bypasses the etiological connotation of alternative terms and avoids inappropriate context. Namely, previous studies referred to allozymes that were observed at high frequency in hybrid zones, but are absent or rare in parental taxa as "the rare allele phenomenon".^[2][4][5] These alleles can have increased frequencies up to a point of the allele becoming the most common one in the hybrid zone, rendering the term "the rare allele phenomenon" deceptive. Despite this, these two terms have been used interchangeably in literature.

Hybrid populations display the hybrizyme phenomenon by having increased frequencies of certain alleles that are rare or non-existent outside of the hybrid zone. The hybrizyme phenomenon is widespread in hybrid zones of species of snails, crickets, lizards, salamanders, rodents, fish and birds.^[1] Intriguingly, the increased frequency of some of these alleles can have a pronounced effect making them 3-20 times more common in hybrids than in non-hybrid populations.^[6]

Early studies focused on detecting electromorphs for loci that code regulatory and non-regulatory enzymes from several functional classes using allozyme electrophoresis and usually involved loci that were polymorphic in parental populations. The phenomenon has also been detected in a broad range of genetic markers such as intron haplotypes,^[3] microsatellites,^[7] ribosomal DNA spacer variants,^[8] and anonymous SNPs.^[9]

Multiple hypotheses have been proposed to explain the mutational (molecular) origin of hybrizymes. They include gene conversion,^[10] transposable element activity,^[11] post-translational modification, mutations.^{[12][13][14][1]} and intragenic recombination. Some of these hypotheses are rejected by research in the past couple of years, but there is an unambiguous explanation for the mutational origin of hybrizymes. The two hypotheses most often discussed are increased mutation rates and intragenic recombination.

Under the mutational hypothesis, hybrizymes likely arise due to simple point mutations. Sequencing data have indicated this and imply low likelihood that hybrizymes arise as a result of transposition or recombination. Research on pocket gophers and Japanese freshwater crabs confirms that the phenomenon is possibly caused by simple nucleotide substitutions.^{[13][12][15][16]} However, the hypothesis has several weaknesses. It does not explain why normally rare alleles are restricted to a hybrid zone, why polymorphic loci are affected more or offers a mechanism that explains the high frequency of even the rarest variants.^[1]

Intragenic recombination, under certain circumstances, might create new allelic variants at rates higher than the ones associated with regular mutational processes. Under this hypothesis the variant allele would be a mosaic of the parental alleles. The likelihood of this hypothesis was disputed, through sequencing studies.^[14][13][17] Although there is yet no specific explanation for hybrizymes, it is not excluded that hybrizymes are generated by the combined effect of recombination and mutation events, with any recombination trace concealed by succeeding mutations. However, research on Acer species implies that high recombination rates are possible due to acceleration of genetic variation after hybridization.^[8] Furthermore, results are found that indicate that recurrent mutation is unlikely and that support the hypothesis of recombination.^[18]