18.11: Both Actins and Myosins are Encoded by Large Gene Families
- Page ID
- 89029
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Actin may be the most abundant protein in cells! At least six different actin isoforms encoded by a large actin gene family have nearly identical amino acid sequences, all of which are involved in cytoskeletal function. While the \(\beta\)−actin isoform predominates, genes for some isoforms are expressed in a cell-specific manner. In mice, the loss of a \(\gamma\)−actin gene has little effect on the organism, while loss of the \(\beta\)−actin gene in mice is lethal at embryonic stages. So what is the function of \(\gamma\)−actin? Does it even have one? Or is \(\gamma\)−actin a vestigial protein that, like our appendix, once served a now long-lost function? And what about all the other isoforms?
Despite yet undefined functional differences between them, virtually all actin isoforms are decorated by myosin monomers (or S1 heads) and amino acid sequence differences among actins don’t predict dramatically different protein function. These observations make one wonder if most actin isoforms are adaptations, however subtle, such that the absence of one isoform would pose a significant threat to the survival of an organism. So, could isoform differences underlie some as-yet-unidentified physiological advantage to different cells? Or are they simply a bank of mutations lying in wait for natural selection to reveal a new function? Studies in humans show that a nonlethal \(\beta\)−actin mutation correlates with delayed development and later neurological problems (e.g., epilepsy) and kidney and heart abnormalities. Still, people with such mutations can lead nearly normal, healthy lives, suggesting that a maintaining a bank of isoforms offer some protection against such nonlethal mutations.
Mouse embryos unable to make \(\beta\)-actin die. But consider a CRISPR/Cas study in which the \(\beta\)-actin gene was edited to express only \(\gamma\)- actin. Unable to make \(\beta\)-actin, the mice transcribe a hybrid \(\beta / \gamma\)-actin gene and translate this hybrid mRNA into \(\gamma\)-actin. These mice lived normal lives, increasing their \(\gamma\)-actin synthesis to compensate for the missing \(\beta\)-actin. The study concludes that “essential in vivo function of \(\beta\)-actin is provided by the gene sequence independent of the encoded protein isoform.” For more detail, check out Essential β-actin function in alternate isoforms.
Finally, genes encoding variant myosin isoforms comprise a large eukaryotic gene family. All isoforms have ATPase activity and some (if not all) are clearly involved in cell motility. Unique functions are not yet known for the isoforms, but different myosin monomers can decorate actin, and myosins from one species can decorate actin filaments of other species, even across wide phylogenetic distances. Clearly, one can still make a career studying why there are so many isoforms of actin and myosin!