Beschreibung:
<jats:p>
Sequence divergence in cis-regulatory elements is an important mechanism contributing to functional diversity of genes during evolution. Gene duplication and divergence provide an opportunity for selectively preserving initial functions and evolving new activities. Many vertebrates have 39
<jats:italic>Hox</jats:italic>
genes organized into four clusters (
<jats:italic>Hoxa</jats:italic>
–
<jats:italic>Hoxd</jats:italic>
); however, some ray-finned fishes have extra
<jats:italic>Hox</jats:italic>
clusters. There is a single
<jats:italic>Hoxa2</jats:italic>
gene in most vertebrates, whereas fugu (
<jats:italic>Takifugu rubripes</jats:italic>
) and medaka (
<jats:italic>Oryzias latipes</jats:italic>
) have two coparalogous genes [
<jats:italic>Hoxa2</jats:italic>
(
<jats:italic>a</jats:italic>
) and
<jats:italic>Hoxa2</jats:italic>
(
<jats:italic>b</jats:italic>
)]. In the hindbrain, both genes are expressed in rhombomere (r) 2, but only
<jats:italic>Hoxa2</jats:italic>
(
<jats:italic>b</jats:italic>
) is expressed in r3, r4, and r5. Multiple regulatory modules directing segmental expression of chicken and mouse
<jats:italic>Hoxa2</jats:italic>
genes have been identified, and each module is composed of a series of discrete elements. We used these modules to investigate the basis of differential expression of duplicated
<jats:italic>Hoxa2</jats:italic>
genes, as a model for understanding the divergence of cis-regulatory elements. Therefore, we cloned putative regulatory regions of the fugu and medaka
<jats:italic>Hoxa2</jats:italic>
(
<jats:italic>a</jats:italic>
) and -(
<jats:italic>b</jats:italic>
) genes and assayed their activity. We found that these modules direct reporter expression in a chicken assay, in a manner corresponding to their endogenous expression pattern in fugu. Although sequence comparisons reveal many differences between the two coparalogous genes, specific subtle changes in seven cis elements of the
<jats:italic>Hoxa2</jats:italic>
(
<jats:italic>a</jats:italic>
) gene restore segmental regulatory activity. Therefore, drift in subsets of the elements in the regulatory modules is responsible for the differential expression of the two coparalogous genes, thus providing insight into the evolution of cis elements.
</jats:p>