Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals
Why this work is in the frame
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Bibliographic record
Abstract
<ns4:p> <ns4:bold>Background</ns4:bold> : The study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of genes is involved in the synthesis ( <ns4:italic>AANAT</ns4:italic> , <ns4:italic>ASMT</ns4:italic> ) and signaling ( <ns4:italic>MTNR1A</ns4:italic> , <ns4:italic>MTNR1B</ns4:italic> ) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin. </ns4:p> <ns4:p> <ns4:bold>Methods</ns4:bold> : We examined <ns4:italic>AANAT</ns4:italic> , <ns4:italic>ASMT</ns4:italic> , <ns4:italic>MTNR1A</ns4:italic> and <ns4:italic>MTNR1B</ns4:italic> in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact. </ns4:p> <ns4:p> <ns4:bold>Results</ns4:bold> : We report that crocodylians retain intact melatonin genes and express <ns4:italic>AANAT</ns4:italic> and <ns4:italic>ASMT</ns4:italic> in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes. </ns4:p> <ns4:p> <ns4:bold>Conclusions:</ns4:bold> The losses of melatonin synthesis and signaling dates to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species. </ns4:p>
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it