Genetic Basis of Human Morphological Evolution
A major focus of the lab is working to identify the genetic basis for human morphological traits, particularly defining the developmental gentic mechanisms of neocortical expansion and the reorganization of craniofacial skeletal elements in the human lineage. We use both 'Functional Genomics' and more targeted, gene-centric, approaches to identify and functionally characterize human-specific genetic changes. In addition to exploring brain and craniofacial evolution, we are also studying the evolution of pregnancy and testis-specific chromatin remodeling proteins in the human-lineage.
Molecular Mechanisms of Evolution
Determining how the function of genes and proteins originated and diversified during evolution is essential for developing a mechanistic understanding of evolution– both to provide a historical explanation for how biological systems arose and to understand evolution as a process so that we may infer general rules of (molecular) evolutionary change. For example, is the path of mutational change in proteins constrained in such a way that evolution is predictable? Is evolution reversible or does a molecular Dollo's law constrain reversion? And, more generally, how do new functions emerge from existing ones?
We most often explore these questions in the context of regulatory control of gene expression by transcription factors, particularly Hox genes. Regardless of the specific experimental system, however, our goal in these studies is to combine evolutionary inferences with the rigorous experimental methods of molecular biology, biochemistry, and structural biology to develop a complete mechanistic and historical explanation for how complex molecular systems evolve.
Evolution of Pregnancy
We are studying the developmental genetic basis for origin of pregnancy in mammals, a major evolutionary novelty. Using a combination of comparative transcriptomics, functional genomics, and in vitro/in vivo experimental hypothesis testing we are working to determine how genes were recruitted into or lost from uterine expression during the evolution of pregnancy, and eulicidate their roles in implantation and the establishment of pregnancy. We are also working to determine if genes important for the evolution of pregnancy play a role in the etiology of infertility and pathologies of pregnancy such as preeclampsia and preterm birth.
Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals.
(Nov 2011) Nature genetics 43(11):1154-9 PMID:21946353
Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples.
(Aug 2012) Theory in biosciences = Theorie in den Biowissenschaften PMID:22872506
Resurrecting the role of transcription factor change in developmental evolution.
(Sep 2008) Evolution; international journal of organic evolution 62(9):2131-54 PMID:18564379
Adaptive evolution of HoxA-11 and HoxA-13 at the origin of the uterus in mammals.
Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes.
Molecular evolution of evolutionary novelties: the vagina and uterus of therian mammals.
(Nov 2005) Journal of experimental zoology. Part B, Molecular and developmental evolution 304(6):580-92 PMID:16252266
Clitoral and penile size variability are not significantly different: lack of evidence for the byproduct theory of the female orgasm.
() Evolution & development 10(4):396-7 PMID:18638314
Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB.
(Dec 2011) Nature 480(7377):383-6 PMID:22080951
Measuring transcription factor-binding site turnover: a maximum likelihood approach using phylogenies.
The gene regulatory logic of transcription factor evolution.
(Jul 2008) Trends in ecology & evolution 23(7):377-85 PMID:18501470
Did egg-laying boas break Dollo's law? Phylogenetic evidence for reversal to oviparity in sand boas (Eryx: Boidae).
(Jan 2010) Evolution; international journal of organic evolution 64(1):207-16 PMID:19659599
Use with caution: developmental systems divergence and potential pitfalls of animal models.
Evolution of a derived protein-protein interaction between HoxA11 and Foxo1a in mammals caused by changes in intramolecular regulation.
A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13.
(Dec 2008) Journal of molecular evolution 67(6):581-93 PMID:18855040
Live-birth in vipers (Viperidae) is a key innovation and adaptation to global cooling during the Cenozoic.
(Sep 2009) Evolution; international journal of organic evolution 63(9):2457-65 PMID:19563326
Revisiting a classic example of transcription factor functional equivalence: are Eyeless and Pax6 functionally equivalent or divergent?
(Mar 2011) Journal of experimental zoology. Part B, Molecular and developmental evolution 316B(2):93-8 PMID:20853421
Convergent evolution of endometrial prolactin expression in primates, mice, and elephants through the independent recruitment of transposable elements.
(Jan 2012) Molecular biology and evolution 29(1):239-47 PMID:21813467
The "fish-specific" Hox cluster duplication is coincident with the origin of teleosts.
(Jan 2006) Molecular biology and evolution 23(1):121-36 PMID:16162861
ACP5 (Uteroferrin): phylogeny of an ancient and conserved gene expressed in the endometrium of mammals.