Pit-1_Evo.pdf (559.19 kB)
Evolution of the POU1F1 transcription factor in mammals: rapid change of the alternatively-spliced ß-domain
journal contribution
posted on 2023-06-09, 12:37 authored by Michael WallisThe POU1F1 (Pit-1) transcription factor is important in regulating expression of growth hormone, prolactin and TSH ß-subunit, and controlling development of the anterior pituitary cells in which these hormones are produced. POU1F1 is a conserved protein comprising three main domains, an N-terminal transcription activation domain (TAD), a POU-specific domain and a C-terminal homeodomain. Within the TAD, a ß-domain can be inserted by alternative splicing, giving an extended 'ß-variant' with altered properties. Here sequence data from over 100 species were used to assess the variability of POU1F1 in mammals. This showed that the POU-specific domain and homeodomain are very strongly conserved, and that the TAD is somewhat less conserved, as are linker and hinge regions between these main domains. On the other hand, the ß-domain is very variable, apparently evolving at a rate not significantly different from that expected for unconstrained, neutral evolution. In several species stop and/or frameshift mutations within the ß domain would prevent expression of the ß-variant as a functional protein. In most species expression of the ß-variant is low (<5% of total POU1F1 expression). The rate of evolution of POU1F1 in mammals shows little variation, though the lineage leading to dog does show an episode of accelerated change. This comparative genomics study suggests that in most mammalian species POU1F1 variants produced by alternative splicing may have little physiological significance.
History
Publication status
- Published
File Version
- Accepted version
Journal
General and Comparative EndocrinologyISSN
0016-6480Publisher
ElsevierExternal DOI
Volume
260Page range
100-106Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-03-26First Open Access (FOA) Date
2019-01-12First Compliant Deposit (FCD) Date
2018-03-24Usage metrics
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