Cited by 463Animal Vocal Communication and BehaviorNeuroscience and Music PerceptionLanguage and cultural evolution

The DOI matches its Crossref record; 116 of the 117 references it cites were found in a registry or an index; none of the 97 sources its claims cite is checked for support yet.

Convergent transcriptional specializations in the brains of humans and song-learning birds

Open access

Abstract

Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

The paper compares brain transcriptomes of vocal-learning birds and humans and identifies convergent gene expression specializations in song and speech brain regions, especially songbird RA with human laryngeal motor cortex and Area X with human putamen/caudate. It argues that convergent vocal-learning behavior and neural connectivity are accompanied by convergent specialized expression of multiple genes.

Key findings

  • Dynamic programming alignment of anatomical gene expression specialization trees found songbird Area X best aligned to human putamen, ventral striatum to human nucleus accumbens, and RA to the human central sulcus within primary motor cortex (PrG_cs); HVC and LMAN aligned weakly to cingulate cortex, with their highest hypothesized matches to Wernicke’s and Broca’s areas but without significant permutation/FWER support.
  • Statistical tests confirmed Area X–putamen and RA–PrG_cs similarities; 288 genes contributed to shared avian–human striatum specialization, 342 to avian pallium–human cortex, 78 to Area X–putamen, 40 to RA–PrG_cs, and 55 mostly nonoverlapping genes (only 3 overlapping with the 40) to RA analogs–human LMC/dLSC.
  • Across all three vocal-learning avian lineages (songbird, parrot, hummingbird), RA analogs showed stronger convergent specialization with human LMC/dLSC than vocal-nonlearning dove/quail arcopallium; 55 genes were identified, with ~91% decreased expression in RA analogs and human LMC/dLSC, and in situ hybridization of 15 genes gave ~95% true positive rate for differential expression in zebra finch RA.
  • Proteomics identified 81 proteins differentially expressed in zebra finch RA; mRNA–protein correlation was modest but significant (R² = 0.18, P = 9.4 × 10⁻⁵), and top disease categories included movement disorders (P = 8.7 × 10⁻¹⁴, 29 genes).

Methods

  • Six experiments were analyzed: laser-microdissected song nuclei from zebra finches; microarray samples of Area X and ventral striatum; RA analogs and adjacent motor arcopallium across vocal-learning and vocal-nonlearning birds; brainstem vocal and neck motor neurons; 3702 human samples from 231 subregions of six Allen Human Brain Atlas subjects; and 258 macaque cortical-layer samples from 12 regions of four rhesus macaques.
  • Avian samples used a custom zebra finch Agilent oligoarray v2.2; human samples used a human Agilent 8×60K array containing 7473 human–finch orthologous genes; cross-species avian filtering yielded 3044 genes for multi-lineage comparisons, and macaque comparisons used 4702 orthologs.
  • Analyses included anatomical gene expression specialization trees, pairwise distances and Pearson correlations, a dynamic programming alignment preserving hierarchical structure, permutation/FWER tests, linear regression to count shared specialized genes, functional enrichment, in situ hybridization, and nanoscale capillary tandem mass spectrometry.

Limitations

  • The paper states that correlations were low even between biological replicates (mean zebra finch RA vs. adjacent mAC replicate correlation = 0.22), that the analyses do not show the specializations are functionally related to projections or vocal learning and could be a consequence rather than a cause, that HVC/LMAN convergent specializations were not significant, that human premortem vocalizing state was unknown, that brainstem vocal/neck motor neurons could not be aligned to proposed human homologs because they were not isolated in the Allen data, and that macaque data were limited in regions, cortical layers, and ortholog number.
  • Evident from the text: cross-species microarray orthology and filtering may miss genes; human samples were collected 10 to 30 hours postmortem, which may affect RNA profiles; avian samples were from silent adult males, limiting behavioral-state and sex coverage; and no causal manipulation tests gene function in vocal learning.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1126/science.1256846

Cites

116 of 116 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 97 cited sources checked · 0 supported · 0 flagged

Show all 89 claims

  • It may state two separate claims as one. 39
  • Probably not a substantial claim. 14
  • The quote only partly states this claim. 2
52 of 52
  • The authors state this as an assumption.

    The human premortem vocalizing state is unknown, but it is assumed not to prevent identification of convergent gene expression specializations as long as one species was silent, the genes are not sensitive to immediate vocalizing behavior, and human samples were collected 10 to 30 hours postmortem when many vocalizing-regulated gene expression changes have subsided.

    “We do not know the premortem vocalizing state of the humans, but did not expect this to prevent us from identifying convergent gene expression specializations as long as one species was silent (the birds), the genes are not sensitive to immediate vocalizing behavior, and the human samples were collected 10 to 30 hours postmortem, when many of the vocalizing-regulated gene expression changes have”
  • The paper relies on this without support.

    No examples of widespread convergence in gene expression patterns in brain regions involved in convergently evolved behavioral traits were known before this study.

    “However, we are not aware of examples of widespread convergence in gene expression patterns in brain regions involved in convergently evolved behavioral traits.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 117 references

1 of the 117 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. R. Wang thesis Duke University (2011); http://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/5630/Wang_duke_0066D_10911.pdf?sequence=1.

Cited by

Sorted by citations

Items 301–400 of 463

Metadata

Authors
Pfenning, A. R., Hara, E., Whitney, O., Rivas, M. V., Wang, R., Roulhac, P. L., Howard, J. T., Wirthlin, M., Lovell, P. V., Ganapathy, G., Mountcastle, J., Moseley, M. A., Thompson, J. W., Soderblom, E. J., Iriki, A., Kato, M., Gilbert, M. T. P., Zhang, G., Bakken, T., Bongaarts, A., Bernard, A., Lein, E., Mello, C. V., Hartemink, A. J., & Jarvis, E. D.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Oregon Health & Science University (US)
  • Duke University (US)
  • RIKEN Center for Brain Science (JP)
  • University of Copenhagen (DK)
  • Allen Institute for Brain Science (US)
  • Allen Institute for Brain Science, Seattle, WA 98103, USA.
Corresponding author
  • Pfenning, Andreas R.
  • Hartemink, Alexander J.
  • Jarvis, Erich D.
Venue
Science
Published
2014-12-12
Volume
346
Issue
6215
Pages
1256846-1256846
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2052801529
Cited by
463
References
117
Citations by year
2026: 25 · 2025: 40 · 2024: 24 · 2023: 32 · 2022: 36 · 2021: 47 · 2020: 39 · 2019: 38 · 2018: 43 · 2017: 57 · 2016: 33 · 2015: 44 · 2014: 4
FWCI
42.23
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
  • eSpace (Curtin University) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (DP1OD000448)
  • National Institute on Deafness and Other Communication Disorders (R21DC007478, R01DC007218)
  • National Institute of General Medical Sciences (R24GM092842)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Vocal Communication and Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
  • Social Sciences › Cultural Studies › Language and cultural evolution
Keywords
vocal learning, human speech, convergent evolution, brain transcriptome, gene expression, song nuclei, striatum, motor control, brain connectivity, avian vocal learning
MeSH terms
Adult, Animals, Birds, Brain, Brain Mapping, Corpus Striatum, Gene Expression Regulation, Humans, Learning, Male, Motor Cortex, Neural Pathways, Species Specificity, Speech, Transcription, Genetic, Vocalization, Animal, Evolution, Molecular, Finches, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review