The right is more conservative than the left: a postnatal hypothesis of handedness based on mice

Qingqing Wang; Jiesi Wang; Yan Wang; Xin Jin; Zhongsheng Sun

doi:10.1016/j.jgg.2025.11.005

Volume 53 Issue 2

Feb. 2026

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2026 > 53(2): 197-208

PDF( 1934 KB)

The right is more conservative than the left: a postnatal hypothesis of handedness based on mice

doi: 10.1016/j.jgg.2025.11.005

a. Interdisciplinary Science Center, State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
b. College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
c. CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China;
d. BGI Research, Shenzhen, Guangdong 518103, China;
e. HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China;
f. Beijing Children's Hospital, National Center for Children's Health, Beijing 100054, China

Funds:

This work was supported by grants from the National Natural Science Foundation of China, China (32470630 to Z.S.), the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, China (E2CX4115CX to J.W.), and State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, China (SKLA2508 to Y.W.).

Received Date: 2025-11-07
Accepted Date: 2025-11-11
Rev Recd Date: 2025-11-10

Available Online: 2026-02-10

Publish Date: 2026-02-10

Abstract

Abstract

Handedness is a fundamental behavioral trait in humans, with the majority exhibiting right-hand dominance. While its origins remain elusive, it is considered an innate genetic trait. This study demonstrates pawedness in mice (n = 473), comparable to human handedness, as an acquired trait rapidly emerging after limited unilateral paw training. Notably, acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness, as evidenced by stronger stability and greater resistance to reversal. This results in a population right-paw dominance under random training conditions. Moreover, acquired pawedness also exhibits sex differences, with the initial preference proving more malleable in females. These findings unveil the acquired features of pawedness in mice. By illuminating possible behavioral laterality commonalities across species, the study proposes a postnatal hypothesis for the origins of human handedness: it is not an innate genetic trait as traditionally believed, but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.
- Handedness,
- Paw preference,
- Unilateral paw training,
- Right-paw dominance,
- Postnatal hypothesis

FullText(HTML)

References(64)

References

Annett, M., 1999. Left-handedness as a function of sex, maternal versus paternal inheritance, and report bias. Behav. Genet. 29, 103-114.

Betancur, C., Neveu, P.J., Le Moal, M., 1991. Strain and sex differences in the degree of paw preference in mice. Behav. Brain Res. 45, 97-101.

Biddle, F.G., Coffaro, C.M., Ziehr, J.E., Eales, B.A., 1993. Genetic variation in paw preference (handedness) in the mouse. Genome 36, 935-943.

Biddle, F.G., Eales, B.A., 1999. Mouse genetic model for left-right hand usage: context, direction, norms of reaction, and memory. Genome 42, 1150-1166.

Biddle, F.G., Eales, B.A., 2001. Lateral asymmetry of paw usage: phenotypic survey of constitutive and experience-conditioned paw-usage behaviours among common strains of the mouse. Genome 44, 539-548.

Biddle, F.G., Eales, B.A., 2006. Hand-preference training in the mouse reveals key elements of its learning and memory process and resolves the phenotypic complexity in the behaviour. Genome 49, 666-677.

Biddle, F.G., Eales, B.A., 2013. Getting it right: Learning and memory determines hand-preference behavior in the mouse. In: W. E. Crusio, F. Sluyter, R. T. Gerlai, S. Pietropaolo (eds.), Behavioral genetics of the mouse, Vol. 1. Genetics of behavioral phenotypes. Cambridge University Press, pp. 109-127.

Biddle, F.G., Jones, D.A., Eales, B.A., 2001. A two-locus model for experience-conditioned direction of paw usage in the mouse is suggested by dominant and recessive constitutive paw usage behaviours. Genome 44, 872-882.

Bisazza, A., Cantalupo, C., Robins, A., Rogers, L.J., Vallortigara, G., 1996. Right-pawedness in toads. Nature 379, 408.

Campbell, J.M., Marcinowski, E.C., Michel, G.F., 2018. The development of neuromotor skills and hand preference during infancy. Dev. Psychobiol. 60, 165-175.

Carter-Saltzman, L., 1980. Biological and sociocultural effects on handedness: comparison between biological and adoptive families. Science 209, 1263-1265.

Charlton, K., Frasnelli, E., 2023. Does owner handedness influence paw preference in dogs? Animal Cognition. 26, 425-433.

Collins, R.L., 1968. On the inheritance of handedness. I. Laterality in inbred mice. J. Hered. 59, 9-12.

Collins, R.L., 1969. On the inheritance of handedness. II. Selection for sinistrality in mice. J. Hered. 60, 117-119.

Collins, R.L., 1975. When left-handed mice live in right-handed worlds. Science 187, 181-184.

Collins, R.L., 1977. Origins of the sense of asymmetry: Mendelian and non-Mendelian models of inheritance. Ann. N. Y. Acad. Sci. 299, 283-305.

Collins, R.L., 1991. Reimpressed selective breeding for lateralization of handedness in mice. Brain Res. 564, 194-202.

Corballis, M.C., 1997. The genetics and evolution of handedness. Psychol. Rev. 104, 714-727.

Corballis, M.C., 2014. Left brain, right brain: facts and fantasies. PLoS. Biol. 12, e1001767.

Cuellar-Partida, G., Tung, J.Y., Eriksson, N., Albrecht, E., Aliev, F., Andreassen, O.A., Barroso, I., Beckmann, J.S., Boks, M.P., Boomsma, D.I., 2021. Genome-wide association study identifies 48 common genetic variants associated with handedness. Nat. Hum. Behav. 5, 59-70.

Hauser, M.D., Chomsky, N., Fitch, W.T., 2002. The faculty of language: What is it, who has it, and how did it evolve? Science 298, 1569-1579.

Hepper, P.G., McCartney, G.R., Shannon, E.A., 1998. Lateralised behaviour in first trimester human foetuses. Neuropsychologia 36, 531-534.

Hepper, P.G., Shahidullah, S., White, R., 1990. Origins of fetal handedness. Nature 347, 431.

Hepper, P.G., Shahidullah, S., White, R., 1991. Handedness in the human fetus. Neuropsychologia 29, 1107-1111.

Hepper, P.G., Wells, D.L., Lynch, C., 2005. Prenatal thumb sucking is related to postnatal handedness. Neuropsychologia 43, 313-315.

Hicks, R.E., Kinsbourne, M., 1976. Human handedness: a partial cross-fostering study. Science 192, 908-910.

Hopkins, B., Ronnqvist, L., 1998. Human handedness: Developmental and evolutionary perspectives. In: Brian H., Louise R. (eds), The development of sensory, motor and cognitive capacities in early infancy: From sensation to cognition, Routledge, pp. 191-236.

Hopkins, W.D., Phillips, K.A., Bania, A., Calcutt, S.E., Gardner, M., Russell, J., Schaeffer, J., Lonsdorf, E.V., Ross, S.R., Schapiro, S.J., 2011. Hand preferences for coordinated bimanual actions in 777 great apes: implications for the evolution of handedness in hominins. J. Hum. Evol. 60, 605-611.

Kavaklioglu, T., Ajmal, M., Hameed, A., Francks, C., 2016. Whole exome sequencing for handedness in a large and highly consanguineous family. Neuropsychologia 93(Pt B), 342-349.

Li, M., Li, X., Ge, H., Wei, X., 1984. A study of hand preference in children. Information on Psychological Sciences 2, 1-7.

Li, Q., Bian, S., Liu, B., Hong, J., Toth, M., Sun, T., 2013. Establishing brain functional laterality in adult mice through unilateral gene manipulation in the embryonic cortex. Cell Res. 23, 1147-1149.

Longstreth, L.E., 1980. Human handedness: more evidence for genetic involvement. J. Genet. Psychol. 137, 275-283.

Manns, M., Basbasse, Y.E., Freund, N., Ocklenburg, S., 2021. Paw preferences in mice and rats: meta-analysis. Neurosci. Biobehav. Rev. 127, 593-606.

McGrew, W.C., Marchant, L.F., 1997. On the other hand: current issues in and meta-analysis of the behavioral laterality of hand function in nonhuman primates. Am. J. Phys. Anthropol. 104, 201-232.

McManus, C., 2019. Half a century of handedness research: Myths, truths; fictions, facts; backwards, but mostly forwards. Brain Neurosci. Adv. 3, 2398212818820513.

McManus, I., 1987. Left, Right, Hand and Brain: the Right Shift Theory. By M. Annett. Lawrence Erlbaum: New Jersey. 1985. Psychological Medicine 17, 523-525.

McManus, I.C., 1985. Handedness, language dominance and aphasia: a genetic model. Psychol. Med. Monogr. Suppl 8, 1-40.

McManus, I.C., Bryden, M.P., 1992. The genetics of handedness, cerebral dominance, and lateralization. In: I. Rapin, S. J. Segalowitz (eds.), Handbook of neuropsychology, Vol. 6. Elsevier Science, New York, pp. 115-144.

Medland, S.E., Duffy, D.L., Wright, M.J., Geffen, G.M., Hay, D.A., Levy, F., van-Beijsterveldt, C.E., Willemsen, G., Townsend, G.C., White, V., et al., 2009. Genetic influences on handedness: data from 25,732 Australian and Dutch twin families. Neuropsychologia 47, 330-337.

Medland, S.E., Duffy, D.L., Wright, M.J., Geffen, G.M., Martin, N.G., 2006. Handedness in twins: joint analysis of data from 35 samples. Twin Res. Hum. Genet. 9, 46-53.

Ocklenburg, S., Isparta, S., Peterburs, J., Papadatou-Pastou, M., 2019. Paw preferences in cats and dogs: Meta-analysis. Laterality 24, 647-677.

Oldfield, R.C., 1971. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97-113.

Pangle, T.L., 1988. The laws of Plato. University of Chicago Press.

Papadatou-Pastou, M., Martin, M., Munafo, M.R., Jones, G.V., 2008. Sex differences in left-handedness: a meta-analysis of 144 studies. Psychol. Bull. 134, 677-699.

Papadatou-Pastou, M., Ntolka, E., Schmitz, J., Martin, M., Munafo, M.R., Ocklenburg, S., Paracchini, S., 2020. Human handedness: A meta-analysis. Psychol. Bull. 146, 481-524.

Pfeifer, L.S., Schmitz, J., Papadatou-Pastou, M., Peterburs, J., Paracchini, S., Ocklenburg, S., 2022. Handedness in twins: meta-analyses. BMC Psychol. 10, 11.

Prichard, E., Propper, R.E., Christman, S.D., 2013. Degree of handedness, but not direction, is a systematic predictor of cognitive performance. Front. Psychol. 4, 9.

Ramsay, D.S., 1980. Onset of unimanual handedness in infants. Infant Behav. Dev. 3, 377-385.

Reimchen, T.E., Spoljaric, M.A., 2011. Right paw foraging bias in wild black bear (Ursus americanus kermodei). Laterality 16, 471-478.

Ribeiro, A.S., Eales, B.A., Biddle, F.G., 2011. Learning of paw preference in mice is strain dependent, gradual and based on short-term memory of previous reaches. Anim. Behav. 81, 249-257.

Ribeiro, A.S., Eales, B.A., Biddle, F.G., 2013. Short-term and long-term memory deficits in handedness learning in mice with absent corpus callosum and reduced hippocampal commissure. Behav. Brain Res. 245, 145-151.

Ribeiro, A.S., Eales, B.A., Lloyd-Price, J., Biddle, F.G., 2014. Predictability and randomness of paw choices are critical elements in the behavioural plasticity of mouse paw preference. Anim. Behav. 98, 167-176.

Ribeiro, A.S., Lloyd-Price, J., Eales, B.A., Biddle, F.G., 2010. Dynamic agent-based model of hand-preference behavior patterns in the mouse. Adapt. Behav. 18, 116-131.

Saudino, K., McManus, I.C., 1998. Handedness, footedness, eyedness and earedness in the Colorado Adoption Project. Br. J. Dev. Psychol. 16, 167-174.

Schmitz, J., Kumsta, R., Moser, D., Gunturkun, O., Ocklenburg, S., 2018. DNA methylation in candidate genes for handedness predicts handedness direction. Laterality 23, 441-461.

Schmitz, J., Metz, G.A.S., Gunturkun, O., Ocklenburg, S., 2017. Beyond the genome-towards an epigenetic understanding of handedness ontogenesis. Prog. Neurobiol. 159, 69-89.

Sha, Z., Pepe, A., Schijven, D., Carrion-Castillo, A., Roe, J.M., Westerhausen, R., Joliot, M., Fisher, S.E., Crivello, F., Francks, C., 2021. Handedness and its genetic influences are associated with structural asymmetries of the cerebral cortex in 31,864 individuals. Proc. Natl. Acad. Sci. U. S. A. 118, e211309511.

Signore, P., Chaoui, M., Nosten-Bertrand, M., Perez-Diaz, F., Marchaland, C., 1991a. Handedness in mice: comparison across eleven inbred strains. Behav. Genet. 21, 421-429.

Signore, P., Nosten-Bertrand, M., Chaoui, M., Roubertoux, P.L., Marchaland, C., Perez-Diaz, F., 1991b. An assessment of handedness in mice. Physiol. Behav. 49, 701-704.

Sobinov, A.R., Bensmaia, S.J., 2021. The neural mechanisms of manual dexterity. Nat. Rev. Neurosci. 22, 741-757.

Soto, C., Gazquez, J.M.M., Llorente, M., 2022. Hand preferences in coordinated bimanual tasks in non-human primates: a systematic review and meta-analysis. Neurosci. Biobehav. Rev. 141, 104822.

Strockens, F., Gunturkun, O., Ocklenburg, S., 2013. Limb preferences in non-human vertebrates. Laterality 18, 536-575.

Ververs, I.A., de Vries, J.I., van Geijn, H.P., Hopkins, B., 1994. Prenatal head position from 12-38 weeks. II. The effects of fetal orientation and placental localization. Early Hum. Dev. 39, 93-100.

Wiberg, A., Ng, M., Al Omran, Y., Alfaro-Almagro, F., McCarthy, P., Marchini, J., Bennett, D.L., Smith, S., Douaud, G., Furniss, D., 2019. Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics. Brain 142, 2938-2947.

Relative Articles

Supplements(0)

Cited By

Proportional views