Loyola University Chicago

Department of Biology

Craniofacial Genes and Human Evolution

The purpose of this project is to apply an integrated approach joining the traditional anthropological fields of paleontology and morphometrics with the tools of modern genetics, genomics, imaging, and developmental biology, to investigate the developmental and genetic bases of human and non-human primate craniofacial variation and evolution. We are identifying axes of morphological change that have characterized human and primate craniofacial evolution and are identifying genomic regions responsible for craniofacial development and variation in these axes. We integrate genomic studies of the baboon as an observational primate model with corresponding studies of the mouse as an experimental model system in which we can directly examine the developmental genetics of the identified morphological features. We can do this because the underlying developmental processes are homologous among mammals, enabling us to link modern developmental genetics to paleontological data. The goal is to identify genes affecting characteristic bony features of the skull of different species, and to identify signals indicating whether these genes were subject to directional selection during human evolution. The study involves several steps:

1. Morphological variation in living and extinct papionins and humans measured using 3D coordinate data from CT scans are being evaluated with both traditional and geometric morphometric methods to define multivariate dimensions of morphological variation in papionin evolution. Analyses will be conducted with specific attention to observations on the evolution of the hominin face, cranial base, and braincase. 3D coordinates of landmarks homologous in fossil and modern primates will be recorded for each specimen.

2. Genetic mapping is being done on a living primate (baboon) and in the mouse to find quantitative trait loci (QTLs--specific chromosomal locations) that affect the dimensions of craniofacial variation identified in Step 1. The results will be refined using a combination of experimental embryologic and bioinformatic approaches in mice to identify and characterize the roles of positional candidate genes within these QTLs in craniofacial development. Because of the deep phylogenetic conservation of developmental mechanisms, the identified genes are highly likely to have been involved in craniofacial evolution among papionins and hominins.

The primate sample is the pedigreed population of baboons at the Southwest Foundation for Biomedical Research, San Antonio, Texas. Within this large population, we are examining CT scans of 800 skulls of deceased adults of known pedigree, that have already been genotyped at ca. 350 microsatellite markers spaced across the genome. This extensive genealogy allows both quantitative genetic and genome linkage-mapping analyses. 3D coordinates of anatomical landmarks are being scored on the 800 CT scans, and measurements, informed by the evolutionary transformations of interest, will be derived and analyzed for heritability, genetic correlation, and the effects of QTLs, using a whole genome scan approach. QTLs located at this stage will be fine-mapped by strategically spotting the region of interest with additional microsatellite or single nucleotide polymorphisms (SNP) markers that we will identify, to produce reduced sets of positional candidate genes.

The mouse mapping populations consist of various crosses between inbred mice, including a large (N=1045) F 2 LG/J by SM/J intercross, their 1600 F 3 offspring scored at 384 polymorphic SNPs, a F 10 Advanced Intercross line (N = 1250) using 1536 polymorphic SNPs, and in a F 34 Advanced Intercross population (N = 1200) using 3072 SNPs. We use this Advanced Intercross for fine-mapping to sub-centi Morgan (cM) levels. We anticipate finding 10-20 positional candidate genes that may be responsible for the QTL effect, and will use syntenic relationships between mouse, human, chimp, and rhesus genome sequences to locate these homologous primate genes. Selectively increased marker density and mouse--baboon sequence analysis will refine the identification of candidate genes or regulatory regions.

3. Potential candidate genes in a mapped chromosomal location will be tested experimentally in the mouse to see if they are expressed in tissues and times appropriate to the trait that mapped to them. Baboon homologues of QTLs identified in mouse mapping will be identified from rhesus-human-mouse map homology and tested to see whether sequence variation has similar effects in the SFBR genealogy. This will be greatly facilitated by the additional statistical power of a priori linkage or association tests of a single candidate location in the baboon relative to a blind genome scan. The relevance of these genes to hominin evolution can be tested in part by comparing multiple-species whole-genome sequence alignments, to identify signals of natural selection in their coding or nearby regulatory regions.

We will make several resources from this project available to the scientific community, including the identification of candidate genes potentially important in human evolution, 3D coordinate data of mouse and baboon crania made available electronically to scientists interested in morphological variation, and a public archive of all the baboon CT images. The mapping data will enable other researchers to investigate aspects of morphology not considered here.

4. We will also examine the molecular evolution of positional candidate genes in the primates in order to determine whether there are signs of positive selection on genes during the period when their associated phenotypes diverged in various primate lineages.


The Craniofacial Genes and Human Evolution Project Website

Dr. Joan Richtsmeier, Penn State University

Dr. Jeff Rogers, Southwest Foundation for Biomedical Research

Dr. Alan Walker, Penn State University

Dr. Ken Weiss, Penn State University

Dr. Charles Roseman, University of Illinois - Urbana

Grant Funding

Supported by NSF – Biological Anthropology, BCS-0725068

Publications on the Topic

Leamy, L. J., C. P. Klingenberg, E. Sherratt, J B. Wolf, and J. M. Cheverud. 2015. The genetic architecture of fluctuating asymmetry of mandible size and shape in a population of mice: another look. Symmetry, 7:146-163.

Joganic, J. L., K. E. Willmore, C. C. Roseman, J. T. Richtsmeier, J. Rogers, and J. M. Cheverud. 2011. Comparative quantitative genetic analysis of cranial capacity and craniofacial morphology in two closely related primate species. In: Bones, Genetics, and Behavior of Rhesus Macaques: Macaca mulatta of Cayo Santiago and Beyond. Q. Wang (ed.), Springer, New York. pp. 37-60.

Willmore, K. E., J. E. Buikstra, J. M. Cheverud, and J. T. Richtsmeier 2011.  Developmental origins of and covariation between metric and nonmetric cranial traits. In: Bones, Genetics, and Behavior of Rhesus Macaques: Macaca mulatta of Cayo Santiago and Beyond. Q. Wang (ed.), Springer, New York. pp. 61-84.

Miley, D D, M H Baumgartner, C F Hildebolt, J M Cheverud, C C Roseman, D E McLeod, E Reyes, J Rogers. 2011.  Heritability of alveolar bone loss from periodontal disease in a baboon population. Journal of Periodontology, 82: 575-580.

Roseman, C. C, K. E. Willmore, J. Rogers, C. F. Hildebolt, B. E. Sadler, J. T. Richtsmeier, and J. M. Cheverud. 2010. Genetic and environmental contributions to variation in baboon cranial morphology: Implications for the study of human evolution. American Journal of Physical Anthropology 143: 1-12.

Roseman, C. C., J. P. Kenney-Hunt and J. M. Cheverud. 2009. Phenotypic integration without modularity: Testing hypotheses about the distribution of pleiotropic quantitative trait loci in a continuous space. Evolutionary Biology 36:282-291.

Willmore, K. E., C. C. Roseman, J. Rogers, J. M. Cheverud, and J. T. Richtsmeier. 2009. Comparison of mandibular phenotypic and genetic integration between baboon and mouse. Evolutionary Biology 36: 19-36.

Willmore, K. E., C. C. Roseman, J. Rogers, J. T. Richtsmeier and J. M. Cheverud. 2009. Genetic variation in baboon craniofacial sexual dimorphism. Evolution 63: 799-806.

Marriog, G. and J. M. Cheverud. 2009. Size and shape in callimico and marmoset skulls: allometry and heterochrony in the morphological evolution of small anthropoids. In: The Smallest Anthropoids: The Marmoset/Callimico Radiation.  S. M. Ford, L. M. Porter and, L. C. Davis (eds.). Springer, New York. pp. 331-354.

Ackermann, R, Rogers, J & Cheverud, J. (2006) 'Identifying the morphological signatures of hybridization in primate and human evolution', Journal of Human Evolution, vol. 51, pp. 632-645. doi:10.1016/j.jhevol.2006.07.009 [pdf]