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Evolution of a new function by degenerative mutation in cephalochordate steroid receptors.

Bridgham JT, Brown JE, Rodríguez-Marí A, Catchen JM, Thornton JW - PLoS Genet. (2008)

Bottom Line: BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR.These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR.Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models.

View Article: PubMed Central - PubMed

Affiliation: Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, Oregon, United States of America.

ABSTRACT
Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models.

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BfER and BfSR are co-expressed.Alternating cross-sections of adult animals were probed with digoxigenin-labelled RNAs for Bfer, Bfsr, or Vasa, a germ cell marker. A–F) In adult females, expression of Bfer and Bfsr are co-localized in the cytoplasm of oocytes in the ovary (o); er is also weakly expressed in the female gill bars (g). The negative control experiment with no probe (inset in A) shows no endogenous alkaline phosphatase activity. G–L) In adult males Bfer and Vasa are expressed only in a single cell layer of early spermatogonia in the testicular epithelium, but Bfsr is expressed throughout testes (t). Myotome (m) and notochord (n) are also labeled. Scale bars are indicated.
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pgen-1000191-g006: BfER and BfSR are co-expressed.Alternating cross-sections of adult animals were probed with digoxigenin-labelled RNAs for Bfer, Bfsr, or Vasa, a germ cell marker. A–F) In adult females, expression of Bfer and Bfsr are co-localized in the cytoplasm of oocytes in the ovary (o); er is also weakly expressed in the female gill bars (g). The negative control experiment with no probe (inset in A) shows no endogenous alkaline phosphatase activity. G–L) In adult males Bfer and Vasa are expressed only in a single cell layer of early spermatogonia in the testicular epithelium, but Bfsr is expressed throughout testes (t). Myotome (m) and notochord (n) are also labeled. Scale bars are indicated.

Mentions: The hypothesis that BfER inhibits BfSR-mediated transcription predicts that the two genes should be coexpressed in some but not all tissues in vivo. We characterized the expression of BfER and BfSR in cross-sections of adult B. floridae by in situ hybridization. In females, transcripts of both genes are abundant in the cytoplasm of oocytes at multiple stages of differentiation (Figure 6, A–F) in a pattern identical to Vasa, a germ cell marker [80]. In addition, the Bfer transcript, but not Bfsr, is weakly expressed in female gills. In males (Figure 6, G–L), Bfsr is expressed broadly throughout the testes, in cells apparently at all stages of spermatogenesis. Bfer, in contrast, is expressed solely in the germinal epithelium of the testis, in a narrow band of cells that are likely to be early spermatogonia based on the expression of Vasa and their basal location within the testis [81]–[83]. These results are consistent with a role for the BfER and BfSR in regulating gonadal function. Because BfER suppresses the transcriptional activity of BfSR and these genes are coexpressed, we conclude that BfER functions, at least in part, as a competitive inhibitor of BfSR activity in vivo.


Evolution of a new function by degenerative mutation in cephalochordate steroid receptors.

Bridgham JT, Brown JE, Rodríguez-Marí A, Catchen JM, Thornton JW - PLoS Genet. (2008)

BfER and BfSR are co-expressed.Alternating cross-sections of adult animals were probed with digoxigenin-labelled RNAs for Bfer, Bfsr, or Vasa, a germ cell marker. A–F) In adult females, expression of Bfer and Bfsr are co-localized in the cytoplasm of oocytes in the ovary (o); er is also weakly expressed in the female gill bars (g). The negative control experiment with no probe (inset in A) shows no endogenous alkaline phosphatase activity. G–L) In adult males Bfer and Vasa are expressed only in a single cell layer of early spermatogonia in the testicular epithelium, but Bfsr is expressed throughout testes (t). Myotome (m) and notochord (n) are also labeled. Scale bars are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2527136&req=5

pgen-1000191-g006: BfER and BfSR are co-expressed.Alternating cross-sections of adult animals were probed with digoxigenin-labelled RNAs for Bfer, Bfsr, or Vasa, a germ cell marker. A–F) In adult females, expression of Bfer and Bfsr are co-localized in the cytoplasm of oocytes in the ovary (o); er is also weakly expressed in the female gill bars (g). The negative control experiment with no probe (inset in A) shows no endogenous alkaline phosphatase activity. G–L) In adult males Bfer and Vasa are expressed only in a single cell layer of early spermatogonia in the testicular epithelium, but Bfsr is expressed throughout testes (t). Myotome (m) and notochord (n) are also labeled. Scale bars are indicated.
Mentions: The hypothesis that BfER inhibits BfSR-mediated transcription predicts that the two genes should be coexpressed in some but not all tissues in vivo. We characterized the expression of BfER and BfSR in cross-sections of adult B. floridae by in situ hybridization. In females, transcripts of both genes are abundant in the cytoplasm of oocytes at multiple stages of differentiation (Figure 6, A–F) in a pattern identical to Vasa, a germ cell marker [80]. In addition, the Bfer transcript, but not Bfsr, is weakly expressed in female gills. In males (Figure 6, G–L), Bfsr is expressed broadly throughout the testes, in cells apparently at all stages of spermatogenesis. Bfer, in contrast, is expressed solely in the germinal epithelium of the testis, in a narrow band of cells that are likely to be early spermatogonia based on the expression of Vasa and their basal location within the testis [81]–[83]. These results are consistent with a role for the BfER and BfSR in regulating gonadal function. Because BfER suppresses the transcriptional activity of BfSR and these genes are coexpressed, we conclude that BfER functions, at least in part, as a competitive inhibitor of BfSR activity in vivo.

Bottom Line: BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR.These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR.Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models.

View Article: PubMed Central - PubMed

Affiliation: Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, Oregon, United States of America.

ABSTRACT
Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models.

Show MeSH
Related in: MedlinePlus