Hybrid Animal Reproduction Doomed by Protein Imbalances

Mules and other hybrids aren't fertile. But why is that exactly? Scientists may have no uncovered the genetic reason. It turns out that differences in the levels--but not necessarily the sequences--of certain key proteins are crucial in mediating reproductive isolation.

In the early 20^th century, scientists developed a theoretical model to explain exactly why distinct species that share the same common ancestor soon diverge to such an extent that their hybrids are unable to reproduce. This model is based on the fact that certain genes evolve more rapidly than others, and in a manner that ensures that they function well within each of the diverging populations, but interfere when brought together in a hybrid genome.

These genes are actually referred to as Dobzhansky-Muller gene pairs, or hybrid-incompatibility pairs. Yet while several of these gene pairs have been isolated, their function has remained unclear. That's why the researchers decided to find out exactly what these genes were doing.

In this particular study, the researchers looked at the functions of the genes Lmr (Lethal male rescue) and Hmr (Hybrid male rescue). These genes form a Dobzhansky-Muller gene pair in hybrid matings between fruit flies.

So what did they find? It turns out that the proteins encoded by the genes Hmr and Lmr form a molecular complex which binds to the centromeric regions of the chromosomes and play an important role in chromosome segregation later in cell division. While the two fruit flies that produced a hybrid can synthesize HMR and LHR proteins, they make these gene products in very different amounts.

It's these differing amounts that truly impact a hybrid's ability to reproduce. In hybrid cells, HMR-LHR complexes are formed in much larger amounts than in the cells of the parental species. In addition, this increase cannot be accommodated by the number of centromeric binding sites available to the hybrid. This, in particular, is responsible for hybrid lethality.

"In addition to the proteins HMR and LHR that we have focused on, other factors have been identified which are involved in mediating reproductive isolation between species," said Axel Imhof, one of the researchers, in a news release. "In future experiments, we intend to look at these proteins in more detail, and will analyze their functions in true species and their hybrids."

The findings are published in the journal Developmental Cell.