= Solution
\b[Visible divergence and reproductive incompatibility measure different outcomes of <evolution>.] A few changes in a <gene regulatory network> can transform a conspicuous <phenotype>, whereas differences in the machinery of <meiosis> or <biological development> can prevent reproduction without greatly changing adult appearance. Neither membership of the same genus nor morphological similarity specifies divergence time or the extent of <reproductive isolation>.
First separate barriers. <premating isolation> can arise through differences in courtship, habitat or breeding season even when a forced cross produces fertile offspring. <postzygotic isolation> concerns the survival or fertility of the offspring themselves. Thus fertile captive <hybrids> do not refute substantial <reproductive isolation> in nature: they may never encounter suitable mates, may have intermediate ecological requirements, or may be unattractive to both parental <biological populations>. Under the <biological species concept>, the relevant issue is effective <gene flow> among natural <biological populations>, not the success of one laboratory mating. Conversely, a laboratory failure can reflect husbandry rather than an intrinsic incompatibility.
Rapid visible divergence is especially plausible when <sexual selection> changes plumage or other signals, or <natural selection> changes a feeding structure. Such changes can involve a small part of the <genome>, leaving most interactions required for fertility compatible. In Darwin's finches, <genome> comparisons associated an <ALX1> region with beak shape and also revealed interspecific <gene flow>. This is an example of conspicuous adaptive differentiation coexisting with exchange of <alleles>, rather than evidence that all avian <hybrids> are fertile.<Evolution of Darwin's finches and their beaks revealed by genome sequencing by Sangeet Lamichhaney and others>[Results on interspecific gene flow and the ALX1 haplotype association with beak shape]{ref} Continued <gene flow> can itself help maintain compatibility through much of the <genome> while divergent <natural selection> preserves differences at selected <genetic loci>.
For cryptic incompatibility, consider a <Dobzhansky-Muller incompatibility>. Two lineages start with compatible <alleles> $a,b$. One evolves $A$ in the presence of $b$, while the other evolves $B$ in the presence of $a$. Each change is tolerable in its own <genetic background>, but the combination $A,B$ disrupts function in <hybrids>. This requires neither lineage to pass through a low-fertility intermediate. Such <epistasis> can affect <spermatogenesis>, <chromosome> pairing, or interactions between nuclear and <mitochondrial genomes>, while leaving the adult body plan nearly unchanged. The relevant changes can arise through <natural selection>, <genetic drift>, or conflict over inheritance; adaptive divergence in external form is not required.
A particularly informative mammalian experiment concerns <PRDM9>, which helps specify <recombination hotspots>. In a particular house-mouse cross, changing its <DNA>-binding region to the corresponding human sequence restored <chromosome> pairing and male fertility. The experiment implicates compatibility between a <genetic recombination> regulator and its binding sites, rather than visible morphological divergence. Crucially, this was a rescue in a specified cross and <genetic background>, not a demonstration that <PRDM9> explains all mammalian <speciation>.<Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice by Benjamin Davies and others>[Figure 1 and section “Humanizing Prdm9 restores hybrid fertility”; parental-background and engineered-allele comparisons]{ref}
Comparative work on birds lacking <PRDM9> found relatively stable <recombination hotspots> associated with functional genomic features.<Stable recombination hotspots in birds by Sonal Singhal and others>[Science 350, pp. 928–932; maps inferred from two finch species and comparisons of hotspot conservation]{ref} This suggests a possible difference in the routes to incompatibility: turnover of <PRDM9> and its targets is unavailable in those lineages. The inference is mechanistic, however; hotspot stability by itself does not demonstrate that avian <hybrids> will be fertile.
Differences in <karyotypes> provide another mechanism. A balanced <chromosomal rearrangement> can have little visible effect in either parent yet cause faulty pairing or unbalanced <gametes> in a <heterozygous> <hybrid>. However, a different <chromosome> count alone does not prove sterility: the arrangement and segregation behavior matter. Differences in <genomic imprinting> may also disturb <placental development> or embryonic growth in mammalian crosses, sometimes producing direction-dependent outcomes. Parent-of-origin growth abnormalities and disrupted <genomic imprinting> in particular rodent <hybrids> provide evidence that this mechanism can matter.<Genomic imprinting is disrupted in interspecific Peromyscus hybrids by Paul B. Vrana and others>[Nature Genetics 20, pp. 362–365; reciprocal-cross growth abnormalities and allelic expression]{ref} These are hypotheses to test in the relevant lineages, not a universal explanation for the bird–mammal comparison.
The sex of the offspring matters. <Haldane's rule> predicts that, when one sex of first-generation <hybrids> is absent, rare or sterile, it tends to be the <heterogametic sex>: typically XY males in mammals and ZW females in birds.<Sex ratio and unisexual sterility in hybrid animals by J. B. S. Haldane>[Journal of Genetics 12, pp. 101–109; formulation of the heterogametic-sex pattern]{ref} Recessive incompatibilities on a <sex chromosome> can be exposed when there is no corresponding second copy; rapid <evolution> of reproductive functions can contribute too. Therefore a report of fertile avian males is insufficient without testing females. The rule predicts a sex bias in a given cross, not that birds as a class have weaker <reproductive isolation>.
To discriminate these mechanisms, compare multiple independently diverged pairs, match their estimated divergence times using <phylogenetics>, and avoid treating taxonomic rank as a clock. Perform reciprocal crosses with parental within-lineage controls; measure <fertilization>, embryonic survival, both sexes' fertility, and second-generation and backcross success. A fertile first generation can conceal <hybrid breakdown> after <genetic recombination> disrupts coadapted combinations. Pair <karyotype> analysis and observations of <meiosis> with <genome> mapping and carefully controlled rescue experiments. Field measurements of mating and ancestry then determine whether compatibility translates into <gene flow>. \b[The contrast is explained by different rates and genetic targets of visible divergence and reproductive divergence, with sex, cross direction, ancestry and assay conditions determining the observed outcome.]
Back to article page
