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.
Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells.
(2014 Oct) Nat Chem
. 2014 Oct;6(10):885-92. doi: 10.1038/nchem.2021. Epub 2014 Aug 11. 25242483
Comparative transcriptomic analysis of cultivated limbal epithelium and donor corneal tissue reveals altered wound healing gene expression.
(2014) Invest Ophthalmol Vis Sci
. 2014 Aug 14;55(9):5795-805. doi: 10.1167/iovs.14-14664. 25125605
A model based criterion for gene expression calls using RNA-seq data.
(2013 Sep) Theory Biosci
. 2013 Sep;132(3):159-64. doi: 10.1007/s12064-013-0178-3. Epub 2013 Apr 25. 23615947
Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs.
(2013 Apr) PLoS Genet
. 2013 Apr;9(4):e1003470. doi: 10.1371/journal.pgen.1003470. Epub 2013 Apr 25. 23637635
Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples.
(2012 Dec) Theory Biosci
. 2012 Dec;131(4):281-5. doi: 10.1007/s12064-012-0162-3. Epub 2012 Aug 8. 22872506
ACP5 (Uteroferrin): phylogeny of an ancient and conserved gene expressed in the endometrium of mammals.
(2012 Apr) Biol Reprod
. 2012 Apr 27;86(4):123. doi: 10.1095/biolreprod.111.097964. Print 2012 Apr. 22278982
Convergent evolution of endometrial prolactin expression in primates, mice, and elephants through the independent recruitment of transposable elements.
(2012 Jan) Mol Biol Evol
. 2012 Jan;29(1):239-47. doi: 10.1093/molbev/msr189. Epub 2011 Aug 2. 21813467
Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB.
(2011 Dec) Nature
. 2011 Nov 13;480(7377):383-6. doi: 10.1038/nature10595. 22080951
Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals.
(2011 Nov) Nat Genet
. 2011 Sep 25;43(11):1154-9. doi: 10.1038/ng.917. 21946353
Evolution of a derived protein-protein interaction between HoxA11 and Foxo1a in mammals caused by changes in intramolecular regulation.
(2011 Aug) Proc Natl Acad Sci U S A
. 2011 Aug 9;108(32):E414-20. doi: 10.1073/pnas.1100990108. Epub 2011 Jul 25. 21788518
Revisiting a classic example of transcription factor functional equivalence: are Eyeless and Pax6 functionally equivalent or divergent?
(2011 Mar) J Exp Zool B Mol Dev Evol
. 2011 Mar 15;316B(2):93-8. doi: 10.1002/jez.b.21373. Epub 2010 Sep 17. 20853421
Did egg-laying boas break Dollo's law? Phylogenetic evidence for reversal to oviparity in sand boas (Eryx: Boidae).
(2010 Jan) Evolution
. 2010 Jan;64(1):207-16. doi: 10.1111/j.1558-5646.2009.00790.x. Epub 2009 Jul 30. 19659599
(2010 Jan) Curr Biol
. 2010 Jan 26;20(2):R48-52. doi: 10.1016/j.cub.2009.11.010. 20129035
Measuring transcription factor-binding site turnover: a maximum likelihood approach using phylogenies.
(2009) Genome Biol Evol
. 2009 May 25;1:85-98. doi: 10.1093/gbe/evp010. 20333180
Live-birth in vipers (Viperidae) is a key innovation and adaptation to global cooling during the Cenozoic.
(2009 Sep) Evolution
. 2009 Sep;63(9):2457-65. doi: 10.1111/j.1558-5646.2009.00733.x. Epub 2009 Jun 26. 19563326
HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards inferring the core transcriptional regulators of decidual genes.
(2009) PLoS One
. 2009 Sep 3;4(9):e6845. doi: 10.1371/journal.pone.0006845. 19727442
Use with caution: developmental systems divergence and potential pitfalls of animal models.
Multiple chromosomal rearrangements structured the ancestral vertebrate Hox-bearing protochromosomes.
(2009 Jan) PLoS Genet
. 2009 Jan;5(1):e1000349. doi: 10.1371/journal.pgen.1000349. Epub 2009 Jan 23. 19165336
A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13.
(2008 Dec) J Mol Evol
. 2008 Dec;67(6):581-93. doi: 10.1007/s00239-008-9156-7. 18855040
Resurrecting the role of transcription factor change in developmental evolution.
(2008 Sep) Evolution
. 2008 Sep;62(9):2131-54. doi: 10.1111/j.1558-5646.2008.00440.x. Epub 2008 Jun 28. 18564379
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals.
(2008 Sep) Proc Natl Acad Sci U S A
. 2008 Sep 30;105(39):14928-33. doi: 10.1073/pnas.0802355105. Epub 2008 Sep 22. 18809929
The gene regulatory logic of transcription factor evolution.
(2008 Jul) Trends Ecol Evol
. 2008 Jul;23(7):377-85. doi: 10.1016/j.tree.2008.03.006. Epub 2008 May 22. 18501470
Clitoral and penile size variability are not significantly different: lack of evidence for the byproduct theory of the female orgasm.
(2008 Jul) Evol Dev
. 2008 Jul-Aug;10(4):396-7. doi: 10.1111/j.1525-142X.2008.00248.x. 18638314
Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes.
Adaptive evolution of Hox-gene homeodomains after cluster duplications.
The "fish-specific" Hox cluster duplication is coincident with the origin of teleosts.
(2006 Jan) Mol Biol Evol
. 2006 Jan;23(1):121-36. Epub 2005 Sep 14. 16162861
Molecular evolution of evolutionary novelties: the vagina and uterus of therian mammals.
(2005 Nov) J Exp Zool B Mol Dev Evol
. 2005 Nov 15;304(6):580-92. 16252266
Adaptive evolution of HoxA-11 and HoxA-13 at the origin of the uterus in mammals.