Snap, phenotype, genotype and fitness
One of the main criticisms of the population genetic pillar of the modern evolutionary synthesis was that too often it was a game of “beanbag genetics”. In other words population geneticists treated genes as discrete independent individual elements within a static sea. R.A. Fisher and his acolytes believed that the average effect of fluctuations of genetic background canceled out as there was no systematic bias, and could be ignored in the analysis of long term evolutionary change. Classical population genetics focused on genetic variation as abstract elementary algebras of the arc of particular alleles (or several alleles). So the whole system was constructed from a few spare atomic elements in a classic bottom-up fashion, clean inference by clean inference. Naturally this sort of abstraction did not sit well with many biologists, who were trained in the field or in the laboratory. By and large the conflict was between the theoretical evolutionists, such as R. A. Fisher and J. B. S. Haldane, and the experimental and observational biologists, such as Theodosius Dobzhansky and Ernst Mayr (see Sewall Wright and Evolutionary Biology for a record of the life and ideas of a man who arguably navigated between these two extremes in 20th century evolution because of his eclectic training). With the discovery that DNA was the specific substrate through which Mendelian genetics and evolutionary biology unfolded physically from generation to generation a third set of players, the molecular biologists, entered the fray.
The details of genetics, the abstract models of theorists, the messy instrumentalism of the naturalists, and the physical focus of the molecular researchers, all matter. Through the conflicts between geneticists, some arising from genuine deep substantive disagreement, and some from different methodological foci, the discipline can enrich our understanding of biological phenomena in all its dimensions. Genomics, which canvasses the broad swaths of the substrate of inheritance, DNA, is obviously of particular fascination to me, but we can also still learn something from old fashioned genetics which narrows in on a few genes and their particular dynamics.
A new paper in PLoS Biology, Cryptic Variation between Species and the Basis of Hybrid Performance, uses several different perspectives to explore the outcomes of crossing different species, in particular the impact on morphological and gene expression variation. You’ve likely heard of hybrid vigor, but too often in our society such terms are almost like black-boxes which magically describe processes which are beyond our comprehension (hybrid vigor and inbreeding depression freely move between scientific and folk genetic domains). This paper attempts to take a stab at peeling pack the veil and gaining a more fundamental understanding of the phenomenon. First, the author summary:
A major conundrum in biology is why hybrids between species display two opposing features. On the one hand, hybrids are often more vigorous or productive than their parents, a phenomenon called hybrid vigor or hybrid superiority. On the other hand they often show reduced vigour and fertility, known as hybrid inferiority. Various theories have been proposed to account for these two aspects of hybrid performance, yet we still lack a coherent account of how these conflicting characteristics arise. To address this issue, we looked at the role that variation in gene expression between parental species may play. By measuring this variation and its effect on phenotype, we show that expression for specific genes may be free to vary during evolution within particular bounds. Although such variation may have little phenotypic effect when each locus is considered individually, the collective effect of variation across multiple genes may become highly significant. Using arguments from theoretical population genetics we show how these effects might lead to both hybrid superiority and inferiority, providing fresh insights into the age-old problem of hybrid performance.
There are various ways one presumes that hybrid vigor could emerge. One the one hand the parental lines may be a bit too inbred and therefore have a heavier than ideal load of deleterious alleles which express recessively. Since two lineages will likely have different deleterious alleles, crossing them will result in immediate complementation and masking of the deleterious alleles in heterozygote state. Another model is that two different alleles when combined in heterozygote state have a synergistic fitness effect. We generally know of heterozygote advantage in cases where there’s balancing selection, so that one of the homozygotes is actually far less fit than the other, but the fitness of the heterozygote is superior to both homozygotes. But that is not a necessity, and presumably there could be cases where both homozygotes are of equal fitness, but the heterozygote is of marginally greater fitness.
As for hybrid inferiority, a simple model for that is that lineages have co-adapted complexes of genes which are enmeshed in gene-gene networks. These networks are finely tuned by evolution and introduction of novel alleles from alien lineages may lead in destabilization of the sensitive web of interconnections. This model taken to an extreme is a scenario whereby speciation could occur if two lineages become mutually exclusive on a particular genetic complex which is “mission critical” to biological machinery (imagine that the gene involved in spermatogenesis is effected).
These stories are fine as it goes, but they do have something of an excessively ad hoc aspect. A little light on formalization and heavy on exposition. In this paper the authors aim to fix that problem. To explore genetic interactions in hybrids, and how they effect gene expression, they selected the genus Antirrhinum as their model. These are also known as “snapdragons.” Like many plants Antirrhinum species can hybridize rather easily across species barriers. They observe the effect of taking genes from a set of species and placing them in the genetic background of another. In particular they are focusing on A. majus, hybridizing it with a variety of other Antirrhinum species, as well as introgressing alleles from the other species onto a A. majus genetic background (so an allele on a specific gene is placed within the genome of A. majus).
Just as they focus on a specific genus of organism, so they also focus on a specific set of genes and the molecular and developmental genetic phenomenon associated with those genes. The genes are CYC and RAD, which are located near each other genomically, with CYC being a cis-acting regulator of RAD. In other words, CYC modulates the expression of RAD which is on the same chromosome. Variance in gene expression simply defines the concrete difference in levels of protein product. Mutant variants of CYC and RAD, cyc and rad, are created by insertion of transposons. Insertion of transposons can abolish gene expression, resulting in removal or alteration of function. What is that function? I’m rather weak on botanical morphology, so I’m going to be cursory on this particular issue lest a reader correct me strenuously for misapplication of terminology. So I’ll show you a figure:
I added the labels. C is basically what majus should look like, while G is a totally “ventralized” mutant. B and F approach wild type, but the other outcomes are more mixed. Note the genotypes in the small print. Table 1 measures the expression levels of the gene product for the various genotype:
Look at the first row; mutant variants of CYC which are nonfunctional reduce normal copies of RAD down to 20% levels of gene expression. That’s because CYC is a transcriptional regulator of RAD. The process is not reversed. RAD lacking functionality does not impact CYC (last row). Finally, the heterozygote states does result in reduced dosage of the gene product. Though the phenotypes might be closer to wild type than the mutant, the molecular expression of the gene is substantially changed. This is one of the issues which is always important to remember: the extent of dominance exhibited by a sequence of phenotypes consequent from a particular genotype may vary dependent on which phenotype you are a highlighting. On a molecular level there is incomplete dominance. Additive effects. On the level of exterior morphology there is more perceived dominance. This is not even addressing the issue of pleiotropy, where the same gene may have dominant and recessive expression on two different traits simultaneously in inverted directions (i.e., the recessively expressed allele in trait A may be dominant in B, and vice versa).
Figure 1 shows the different allelic expression levels in hybrids of Antirrhinum species. But what about the impact of the combinations on phenotype? I’ve reedited figure 4 so it fits better on this page: