Protein imbalances doom hybrids

Why do crosses between closely related species fail to produce fertile
hybrids? A new study led by Professor Axel Imhof of
Ludwig-Maximilians-Universitaet (LMU) in Munich shows that differences
in the levels – not necessarily the sequences – of certain key
proteins are crucial in mediating reproductive isolation.
Two individuals are defined as belonging to the same biological
species, if matings between them give rise to viable and fertile
offspring. Crosses between closely related, but already distinct,
species produce hybrid offspring that are either inviable or sterile,
and thus cannot give rise to a self-propagating hybrid lineage.
In the early 20th century, geneticists and evolutionary biologists
developed a theoretical model to explain why distinct species that
share the same common ancestor soon diverge to such an extent that
their hybrids are unable to reproduce. This model postulates that
certain genes evolve more rapidly than others – and in a manner which
ensures that they function well within each of the diverging
populations, but interfere with one another when brought together in
hybrid genomes.
Such genes are referred to as Dobzhansky-Muller gene pairs, or
hybrid-incompatibility genes. “Although several Dobzhansky-Muller gene
pairs have been isolated in the last five years, their function
remained essentially unclear prior to our study,” says Professor Axel
Imhof of LMU’s Adolf Butenandt Institute. In their new study, he and
his team have now characterized the functions of the genes Lmr (Lethal
male rescue) and Hmr (Hybrid male rescue), which form a
Dobzhansky-Muller gene pair in hybrid matings between fruitflies
belonging to the closely related Drosophila species D. melanogaster
and D. simulans.
Hybrid males produced by crosses between these two species are
inviable, while the female hybrids are viable but sterile. Imhof’s
group has now shown that the proteins encoded by the genes Hmr and Lhr
form a molecular complex, which binds to the centromeric regions of
chromosomes, i.e., at the site of the typical constriction found in
paired sister chromosomes prior to cell division, and play an
important role in chromosome segregation later in cell division.
The problem for the hybrids lies in the fact that, although both D.
melanogaster and D. simulans synthesize HMR and LHR proteins, they
make these gene products in very different amounts.
Thus D. melanogaster makes far more HMR than D. simulans, while the
latter produces LHR in much higher concentrations than D.
melanogaster. Nevertheless, the HMR and LHR proteins retain the
ability to interact with each other, irrespective of their origin.
As a result, in hybrid cells, HMR-LHR complexes are formed in much
larger amounts than in the cells of the parental species. Moreover,
this increase cannot be accommodated by the number of centromeric
binding sites available in the hybrid.
The resulting discrepancy between the amounts of complex and
centromeric binding sites leads to binding of the complex all over the
genome. It is this abnormal distribution of HMR-LHR complexes that is
responsible for hybrid lethality.
These results show that it is the relative level of the proteins
concerned, and not any differences in their amino acid sequences, that
plays the crucial role here. It also encourages the LMU researchers to
search further for species-specific differences in protein levels with
the aid of quantitative proteomics.
“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. “In future experiments, we
intend to look at these proteins in more detail, and will analyze
their functions in true species and their hybrids,” says Imhof. –
Eurasia Review