Figure 9.
In our model, an ancestral mef2 gene existed with distinct expression domains. In this example, ancestral mef2c had expression in the head and the heart. Following whole genome duplication, initially the regulatory and coding sequences would be identical. Through divergence and natural selection, factors controlling gene regulation would acquire mutations that dampen, but do not eliminate, some expression domains. In this example, mef2cb expression is dampened in the head. These gene expression changes result in subfunctionalization but with vestigial retention of the original expression. mef2cb is no longer required for craniofacial development, yet traces of the original craniofacial expression remain. The amount of vestigial expression is variable among individuals, resulting in variable buffering against mef2ca mutant phenotypes across a population. Our selective breeding selected on this variable expression resulting in higher paralog expression in the low-penetrance strain compared with the high-penetrance strain. Thus, mef2 paralog expression in the low-penetrance strain resembles the ancestral condition following whole genome duplication, when both copies’ expression profiles were highly similar, and the genes were redundant for craniofacial development.
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