Evolution of the POU1F1 transcription factor in mammals: rapid change of the alternatively-spliced β-domain

Wallis, Michael (2018) Evolution of the POU1F1 transcription factor in mammals: rapid change of the alternatively-spliced β-domain. General and Comparative Endocrinology, 260. pp. 100-106. ISSN 0016-6480

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Abstract

The POU1F1 (Pit-1) transcription factor is important in regulating expression of growth hormone, prolactin and TSH β-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 β-domain can be inserted by alternative splicing, giving an extended 'β-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 β-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 β domain would prevent expression of the β-variant as a functional protein. In most species expression of the β-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.

Item Type: Article
Keywords: Pit-1, POU1F1, β-domain, molecular evolution, evolutionary rates
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QP Physiology > QP0501 Animal biochemistry
Depositing User: Michael Wallis
Date Deposited: 26 Mar 2018 08:29
Last Modified: 26 Mar 2018 08:29
URI: http://sro.sussex.ac.uk/id/eprint/74627

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