Research in the Snyder-Mackler (SMack) lab in the School of Life Sciences and Center for Evolution and Medicine at Arizona State University sits at the nexus of the social environment and the genome. We use molecular genetic techniques to probe the dynamic interaction between the social environment and the genome with the aim of understanding the fitness consequences of behavioral variation.
Broadly, our lab investigates the causes and consequences of variation in the social environment from the molecular to the organismal levels. Our work involves two complementary study systems, which allow us to probe questions central to human health, aging, and evolutionary biology.
Studies of social environmental effects can be difficult to interpret due to the complexity of the human social environment and the inability, due to ethical concerns, to perform experimental manipulations. This has led many researchers to turn to our close genetic relatives, nonhuman primates. Rhesus macaques (Macaca mulatta) are a particularly important model for human social behavior, health, and aging because they exhibit strikingly similar age-related changes in physiological, cognitive, and immune function, but compacted into a lifespan that is 3-4 times shorter. As in humans, the social environment has also been linked to mortality in some nonhuman primates, including close relatives of macaques.
Genomic consequences of the social environment and resilience during aging.
More socially integrated individuals are healthier and live longer than less integrated individuals, and this association is the strongest in the oldest individuals in a population. To identify the molecular underpinnings of this link, we draw behavioral and genomic data from both captive and free-ranging rhesus macaques. We merge cutting-edge functional genomic analyses with behavioral observation methods to study how behavioral variation might insulate individuals from the detrimental effects of social stress on health.
This research has implications for understanding how social stress recapitulates, or even accelerates, the changes seen during normal aging. More broadly, identifying the molecular phenotypes on which natural selection acts will lead to a better understanding of both the evolution of affiliative social behaviors and the well-documented link between sociality and components of fitness.
If you are ever in the Ethiopia, you might find yourself surrounded by thousands of some of the most unique primates on the planet – gelada monkeys. These monkeys are often erroneously called ‘bleeding heart baboons’. Not because they don’t have blazingly red chests (they do!), but because geladas are not actually baboons – just close relatives that diverged ~3-5 million years ago. Historically, monkeys from the geladas’ genus, Theropithecus, ranged across East Africa. Now, it’s just the gelada monkey, Theropithecus gelada, found only in the highlands of Ethiopia — one of our two primary study species.
The immunogenomic consequences of sociality
As part of the Simien Mountains Gelada Research Project, we study how the highly social lives of geladas influences their health, reproduction, and survival. To do so, we draw on over a decade of demographic and behavioral data and combine it with genomic analyses. Here, we can take findings from captive populations and extend them to the field to see how social integration may buffer individuals against more naturalistic stressors in the wild.
High altitude adaptation
One of the primary reasons that geladas endured – unlike their extinct Theropithecus relatives – is due to a panoply of unique adaptations to their resource-scarce, high altitude environment. In the thin air of the gelada’s habitat (≥ 3,000m above sea level), there is a dearth of nutrient rich foods. So the geladas depend almost entirely on the grasses that fill the plateaus – much like a cow. Graminivory is just one of the many gelada adaptations to their high-altitude environment. Others include their ability to thrive so high above sea level. Have geladas converged on similar high altitude adaptions that are also found in the genomes of people living in the Andes or Himalayas? Or has selection led to unique changes specific only to the gelada?
In this line of work we aim to identify signatures of high altitude adaptation in the gelada monkey genome. To do so, we need to sequence the genomes of dozens of geladas from multiple populations, which will require sequencing gelada genomes from non-invasively collected samples. Here, we will draw on techniques that we developed in collaboration with Jenny Tung and Xiang Zhou that allow us to generate genome-scale genetic information from low-quality, non-invasively collected samples as well as the computational tools necessary to analyze such data.
The Goldilocks Effect: Female geladas in mid-sized groups have higher fitness
Snyder-Mackler N, Sanz J, Kohn JN, Voyles TN, Pique-Regi R, Wilson ME, Barreiro LB, Tung J (2018) “Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques.”
Snyder-Mackler N* & Lea AJ* (2018). “Functional genomic insights into the environmental determinants of mammalian fitness.” Current Opinion in Genetics & Development. doi:10.1016/j.gde.2018.08.001
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Madlon-Kay S, Montague MJ, Brent LJN, Ellis S, Zhong B, Snyder-Mackler N, Horvath JE, Skene JHP, Platt ML (2018). “Weak effects of common genetic variation in oxytocin and vasopressin receptor genes on rhesus macaque social behavior.” American Journal of Primatology. doi:10.1002/ajp.22873
Tinsley Johnson E, Snyder-Mackler N, Lu A, Bergman TJ, Beehner JC (2018). “Social and ecological drivers of reproductive seasonality in geladas.” Behavioral Ecology. 29:3, 574–588. doi: 10.1093/beheco/ary008
Belsky D and Snyder-Mackler N (2017). “Invited Commentary: Integrating Genomics and Social Epidemiology—Analysis of Late-Life Low Socioeconomic Status and the Conserved Transcriptional Response to Adversity” American Journal of Epidemiology, doi: 10.1093/aje/kwx145
Snyder-Mackler N and Tung J (2017). “Vasopressin and the neurogenetics of parental care”(“Spotlight” article on Bendesky et al. 2017, Nature) Neuron, 94:1, 9–11, doi: 10.1016/j.neuron.2017.06.027 (* not peer-reviewed)
Schneider-Crease I, Griffin RH, Gomery MA, Dorny P, Noh JC, Handali S, Chastain HM, Wilkins PP, Nunn CL, Snyder-Mackler N, Beehner JC, Bergman TJ (2017). “Non-invasive diagnosis of endemic Taenia serialis infection in a wild primate population” PLoS Neglected Tropical Diseases, doi: 10.1371/journal.pntd.0005709.
Snyder-Mackler N, Pappano DJ (2016). Gelada (Theropithecus). In The International Encyclopedia of Primatology. John Wiley & Sons, doi:10.1002/9781119179313.wbprim0252
Snyder-Mackler N*, Sanz J*, Kohn JN, Brinkworth JF, Morrow S, Shaver AO, Grenier J-C, Pique-Regi R, Johnson ZP, Wilson ME, Barreiro LB, Tung J (2016) “Social status alters immune regulation and response to infection in macaques” Science, 354:6315, 1041-1045, doi: 10.1126/science.aah3580.
Kohn JN, Snyder-Mackler N, Barreiro LB, Johnson ZP, Tung J, Wilson ME (2016) “Dominance rank causally affects personality and glucocorticoid regulation in female rhesus macaques” Psychoneuroendocrinology, 74, 179-188, doi: 10.1016/j.psyneuen.2016.09.005.
Wall JD, Schlebusch SA, Alberts SC, Cox L, Snyder-Mackler N, Nevonen K, Carbone L, Tung J (2016) “Genome-wide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons” Molecular Ecology, 25:14, 3469-3483, doi: 10.1111/mec.13684.
Snyder-Mackler N, Majoros B, Yuan ML, Shaver AO, Gordon JB, Kopp GH, Schlebusch SA, Wall JD, Alberts SC, Mukherjee S, Zhou S, Tung J (2016) “Efficient genome-wide sequencing and low coverage pedigree analysis from non-invasively collected samples.” Genetics, 203:2, 699-714, doi: 10.1534/genetics.116.187492.
Charruau P, Johnston R, Stahler DR, Lea AJ, Snyder-Mackler N, Smith DW, vonHoldt BM, Cole SW, Tung J, Wayne RK (2016) “Pervasive effects of aging on gene expression in wild wolves” Molecular Biology and Evolution, 33:8, 1967-1978, doi: 10.1093/molbev/msw072.
Snyder-Mackler N, Kohn JN, Barreiro LB, Johnson ZP, Wilson ME, & Tung J (2016) – “Social status drives social relationships in groups of unrelated female rhesus macaques.” Animal Behaviour, 111, 307-317, doi: 10.1016/j.anbehav.2015.10.033.
Snyder-Mackler N, Alberts SC, & Bergman TJ (2014) – “The socio-genetics of a complex society: Female gelada monkey relatedness patterns mirror association patterns in a multi-level society” Molecular Ecology, 23:24, 6179-6191, doi: 10.1111/mec.12987.
Snyder-Mackler N, Somel M, & Tung J (2014) – “Shared signatures of social stress and aging in PBMC gene expression profiles.” Aging Cell,13:5, 954-957, doi: 10.1111/acel.12239.
Tinsley Johnson E*, Snyder-Mackler N*, Beehner JC & Bergman TJ (2014) – “Kinship and dominance rank influence the strength of social bonds in female geladas” International Journal of Primatology, 35:1, 288-304, doi:10.1007/s10764-013-9733-5.
Scheider-Crease I*, Snyder-Mackler N*, Jarvey JC & Bergman TJ (2013) – “Molecular identification of Taenia serialis coenurosis in a wild Ethiopian gelada (Theropithecus gelada)” Veterinary Parasitology, 198:1-2, 240-243, doi: 10.1016/j.vetpar.2013.08.015.
Le Roux, A, Snyder-Mackler N, Roberts EK, Beehner JC & Bergman TJ (2013) – “Evidence for tactical concealment in a wild primate” Nature Communications, 4:1462, doi: 10.1038/ncomms2468.
Snyder-Mackler N, Alberts SC & Bergman TJ (2012) – “Concessions of an alpha male? Cooperative defence and shared reproduction in multi-male primate groups.” Proceedings of the Royal Society B: Biological Sciences, 279:1743, 3788-3795. doi: 10.1098/rspb.2012.0842.
Pappano DJ*, Snyder-Mackler N*, Bergman TJ & Beehner JC (2012) – “Social predators in a multi-level society” Animal Behaviour, 84:3, 653-658. doi: 10.1016/j.anbehav.2012.06.021.
Snyder-Mackler N, Beehner JC, Bergman TJ (2012) – “Defining higher levels in the multilevel societies of geladas (Theropithecus gelada)” International Journal of Primatology – 33:5, 1054:1068. doi: 10.1007/s10764-012-9584-5.
Gersick AS, Snyder-Mackler N, White DJ (2012) – “Ontogeny of social skills: social complexity improves mating and competitive strategies in male brown-headed cowbirds” Animal Behaviour, 83:5, 1171–1177. doi: 10.1016/j.anbehav.2012.02.005.
White DJ, Gersick AS & Snyder-Mackler N (2012) – “Social networks and the development of social skills in cowbirds.” Philosophical Transactions of the Royal Society of London B: Biological Sciences, 367:1597, 1892-1900. doi: 10.1098/rstb.2011.0223.
Snyder-Mackler N & White DJ (2011). “The developmental ecology of acoustic sensitivities: reactions to song playbacks by male cowbirds change across their first year of life.” Behaviour, 148:7, 747-764. doi: 10.1163/000579511X575951.
White DJ, Gersick AS, Freed-Brown SG & Snyder-Mackler N (2010). “The ontogeny of social skills: experimental increases in social complexity enhance reproductive success in adult cowbirds.” Animal Behavior, 79:2, 385-390. doi: 10.1016/j.anbehav.2009.11.014.
* denotes co-first authorship.