Human beta globin has held a special place in my heart due to its rather prominent role in the Evolution-Creation ‘debate’. It just got a neat evolutionary upgrade ?
Humans have one kind of hemoglobin when they are infants which has a higher affinity for O2 (alpha globin + gamma globin), because it makes it easier to steal O2 from their mom. Once the babies are out in the real world for a few months, they slowly but steadily shift from making the gamma globin to beta globin, the adult hemoglobin (alpha globin + beta globin).
This transition is a problem for kids with sickle-cell. Their gamma globin subunit is totally fine… but once they transition to using the beta subunit, all hell breaks loose. The mutated betas get together to form fibers that misshape red blood cells (ie, sickle-shaped).
Gene therapy, replacing the ‘bad’ gene with a normally functioning gene, would be a marvelous future option for people with sickle-cell (or designer babies for people who carry the gene), but an option we are pursuing today is how to get people with sickle cell to stop/reduce their production of the beta subunit, and go back to using their fully normal gamma subunit. Even if you can only slightly alter the ratio of gamma:beta, you could provide a useful therapeutic effect for people with sickle-cell– If there is a lot of gamma subunit floating around, then the malfunctioning beta subunits cannot form those fibers as easily.
A neat paper came out earlier this month that help explains the how/why of the gamma–>beta subunit switch in humans, and might give us some ideas on how to alter it:
Turns out, in between the gamma gene and the beta gene, there is a solo LTR. This retroviral promoter competes with the gamma globulin promoter, slowly but surely siphoning off the shared transcription factors, and transferring them to the beta globin promoter. Thus this ERV LTR helps us make the beta subunit instead of the gamma.
When scientists transferred the human hemoglobin locus into mice (mice dont have a gamma, so they couldnt just do this straight in mice), whenever the ERV LTR was deleted, the mice had less beta subunit, and more gamma, well past the point in time after birth they should have switched. In the mice that got the full locus, they transitioned from gamma–>beta normally, like humans do.
This not only provides an alternative pathway for future gene therapy, but it provides a new avenue we can pursue now– Maybe epigenetic modifying drugs could turn down this ERV LTR? Provide some kind of shift back to gamma? But maybe not…? It might be worth trying in people with frequent, painful attacks.
This is also cool evolutionarily. Higher primates (chimpanzees, orangutans, etc) do have this solo LTR, and theyve co-opted it for the gamma–>beta transition. Monkeys dont have this solo LTR, but they still transition just fine, but if you transfer the plain-ol human hemoglobin locus to mice, it doesnt work perfectly. Monkeys figured out a different way to do the transition, outside of the simple locus. So two branches of the evolutionary tree ‘figured out’ different answers to the same problem: how to stop making gamma, and start making beta. Thats super cool!
Whats funny is how Creationists are dealing with this finding. They have no idea what this paper says/means, so they are just sticking with Creationist Claims About ERVs, #6.
The ‘Junk DNA’ Paradigm Continues To Collapse As New Functions Are Discovered For Retrotransposons.The literature continues to flood in demonstrating that so-called ‘junk’ regions of the genome are not junk after all, but serve significant and important functions.
You see, since 1:4,000 of a family of LTRs has been co-opted for use within some hosts (its not necessary in other hosts, and sometimes it is bothersome in the host it has been co-opted in) 4,000:4,000 are 100% useful and perfectly designed. Therefore, there is no such thing as junk DNA, and Jesus Christ is our Lord and Savior and died on The Cross for our sins.