Evolutionary Dynamics of the Alpha-actinin Gene Family

Abstract

The alpha-actinin gene family is a member of the spectrin superfamily of proteins. Other members of this superfamily include the a- and ~-spectrins, ~heavy spectrin and dystrophin. Each member of this superfamily has a unique actin cross-linking distance consequent to the specific number of spectrin repeats within the central repeat region of the superfamily. Alpha-actinin is thought to be the least derived of the spectrin superfamily due to its possession of the smallest number of spectrin repeats. Though many a-actinins are known, the relationships among them are as yet undetermined. I performed phylogenetic analyses on a-actinin sequences to establish the kinship among a-actinin isoforms and to taxonomically treat the sequences. In addition, I sequenced and analyzed a previously unknown rat a-actinin 3. Analyses support four main isoforms of a-actinin. I also investigated homogenizing evolution within the spectrin repeats of the gene family. This was accomplished using gene conversion analyses and a new analysis which implements a continuum of the two known modes of homogenizing evolution: birth-and-death evolution and concerted evolution. This conceptual leap to a continuous model has not previously been made. Furthering these generalized studies of the a-actinin gene family, I used RT-PCR, cloning and automated DNA sequencing to obtain 77bp of sequence for what may be yet another member of the spectrin superfamily, the G3.5 antigen.