Vincent J. Lynch, Ph.D.

Assistant Professor

Office Address: CLSC 325B
Telephone numbre: 773 834 1326

Research Description

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.

Selected Publications

Transposable elements are the primary source of novelty in primate gene regulation.
Trizzino M, Park Y, Holsbach-Beltrame M, Aracena K, Mika K, Caliskan M, Perry GH, Lynch VJ, Brown CD
(2017 Oct) Genome Res. 2017 Oct;27(10):1623-1633. doi: 10.1101/gr.218149.116. Epub 2017 Aug 30. 28855262 (Full Text)

Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.
Dulberger CL, McMurtrey CP, Holzemer A, Neu KE, Liu V, Steinbach AM, Garcia-Beltran WF, Sulak M, Jabri B, Lynch VJ, Altfeld M, Hildebrand WH, Adams EJ
(2017 Jun) Immunity. 2017 Jun 20;46(6):1018-1029.e7. doi: 10.1016/j.immuni.2017.06.002. 28636952 (Full Text)

An Ancient Fecundability-Associated Polymorphism Switches a Repressor into an Enhancer of Endometrial TAP2 Expression.
Mika KM, Lynch VJ
(2016 Nov) Am J Hum Genet. 2016 Nov 3;99(5):1059-1071. doi: 10.1016/j.ajhg.2016.09.002. Epub 2016 Oct 13. 27745831 (Full Text)

TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants.
Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ
(2016 Sep) Elife. 2016 Sep 19;5. pii: e11994. doi: 10.7554/eLife.11994. 27642012 (Full Text)

The Transcriptomic Evolution of Mammalian Pregnancy: Gene Expression Innovations in Endometrial Stromal Fibroblasts.
Kin K, Maziarz J, Chavan AR, Kamat M, Vasudevan S, Birt A, Emera D, Lynch VJ, Ott TL, Pavlicev M, Wagner GP
(2016 Aug) Genome Biol Evol. 2016 Aug 25;8(8):2459-73. doi: 10.1093/gbe/evw168. 27401177 (Full Text)

Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes.
Burrows CK, Kosova G, Herman C, Patterson K, Hartmann KE, Velez Edwards DR, Stephenson MD, Lynch VJ, Ober C
(2016 Jul) PLoS Genet. 2016 Jul 22;12(7):e1005858. doi: 10.1371/journal.pgen.1005858. eCollection 2016 Jul. 27447835 (Full Text)

A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1.
Nnamani MC, Ganguly S, Erkenbrack EM, Lynch VJ, Mizoue LS, Tong Y, Darling HL, Fuxreiter M, Meiler J, Wagner GP
(2016 Jun) Cell Rep. 2016 Jun 7;15(10):2097-2108. doi: 10.1016/j.celrep.2016.04.088. Epub 2016 May 26. 27239043

GENETICS. A copy-and-paste gene regulatory network.
Lynch VJ
(2016 Mar) Science. 2016 Mar 4;351(6277):1029-30. doi: 10.1126/science.aaf2977. 26941305

Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic.
Lynch VJ, Bedoya-Reina OC, Ratan A, Sulak M, Drautz-Moses DI, Perry GH, Miller W, Schuster SC
(2015 Jul) Cell Rep. 2015 Jul 14;12(2):217-28. doi: 10.1016/j.celrep.2015.06.027. Epub 2015 Jul 2. 26146078

Evolutionary forward genomics reveals novel insights into the genes and pathways dysregulated in recurrent early pregnancy loss.
Kosova G, Stephenson MD, Lynch VJ, Ober C
(2015 Mar) Hum Reprod. 2015 Mar;30(3):519-29. doi: 10.1093/humrep/deu355. Epub 2015 Jan 12. 25586782 (Full Text)

Cell-type phylogenetics and the origin of endometrial stromal cells.
Kin K, Nnamani MC, Lynch VJ, Michaelides E, Wagner GP
(2015 Mar) Cell Rep. 2015 Mar 3;10(8):1398-409. doi: 10.1016/j.celrep.2015.01.062. Epub 2015 Feb 26. 25732829

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy.
Lynch VJ, Nnamani MC, Kapusta A, Brayer K, Plaza SL, Mazur EC, Emera D, Sheikh SZ, Grutzner F, Bauersachs S, Graf A, Young SL, Lieb JD, DeMayo FJ, Feschotte C, Wagner GP
(2015 Feb) Cell Rep. 2015 Feb 3;10(4):551-61. doi: 10.1016/j.celrep.2014.12.052. Epub 2015 Jan 29. 25640180 (Full Text)

Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells.
Ko SK, Kim SK, Share A, Lynch VM, Park J, Namkung W, Van Rossom W, Busschaert N, Gale PA, Sessler JL, Shin I
(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.
Gallagher C, Clarke C, Aherne ST, Katikireddy KR, Doolan P, Lynch V, Shaw S, Bobart-Hone A, Murphy C, Clynes M, Power W, O'Sullivan F
(2014 Aug) 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.
Wagner GP, Kin K, Lynch VJ
(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.
Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L, Bourque G, Yandell M, Feschotte C
(2013 Apr) PLoS Genet. 2013 Apr;9(4):e1003470. doi: 10.1371/journal.pgen.1003470. Epub 2013 Apr 25. 23637635 (Full Text)

Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples.
Wagner GP, Kin K, Lynch VJ
(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.
Padua MB, Lynch VJ, Alvarez NV, Garthwaite MA, Golos TG, Bazer FW, Kalkunte S, Sharma S, Wagner GP, Hansen PJ
(2012 Apr) Biol Reprod. 2012 Apr 27;86(4):123. doi: 10.1095/biolreprod.111.097964. Print 2012 Apr. 22278982 (Full Text)

Convergent evolution of endometrial prolactin expression in primates, mice, and elephants through the independent recruitment of transposable elements.
Emera D, Casola C, Lynch VJ, Wildman DE, Agnew D, Wagner GP
(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.
Lynch VJ, May G, Wagner GP
(2011 Nov) 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.
Lynch VJ, Leclerc RD, May G, Wagner GP
(2011 Sep) 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.
Brayer KJ, Lynch VJ, Wagner GP
(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 (Full Text)

Revisiting a classic example of transcription factor functional equivalence: are Eyeless and Pax6 functionally equivalent or divergent?
Lynch VJ, Wagner GP
(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).
Lynch VJ, Wagner GP
(2010 Jan) Evolution. 2010 Jan;64(1):207-16. doi: 10.1111/j.1558-5646.2009.00790.x. Epub 2009 Jul 30. 19659599

Evolutionary novelties.
Wagner GP, Lynch VJ
(2010 Jan) Curr Biol. 2010 Jan 26;20(2):R48-52. doi: 10.1016/j.cub.2009.11.010. 20129035

Live-birth in vipers (Viperidae) is a key innovation and adaptation to global cooling during the Cenozoic.
Lynch VJ
(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.
Lynch VJ, Brayer K, Gellersen B, Wagner GP
(2009 Sep) PLoS One. 2009 Sep 3;4(9):e6845. doi: 10.1371/journal.pone.0006845. 19727442 (Full Text)

Use with caution: developmental systems divergence and potential pitfalls of animal models.
Lynch VJ
(2009 Jun) Yale J Biol Med. 2009 Jun;82(2):53-66. 19562005 (Full Text)

Measuring transcription factor-binding site turnover: a maximum likelihood approach using phylogenies.
Otto W, Stadler PF, Lopez-Giraldez F, Townsend JP, Lynch VJ, Wagner GP
(2009 May) Genome Biol Evol. 2009 May 25;1:85-98. doi: 10.1093/gbe/evp010. 20333180 (Full Text)

Multiple chromosomal rearrangements structured the ancestral vertebrate Hox-bearing protochromosomes.
Lynch VJ, Wagner GP
(2009 Jan) PLoS Genet. 2009 Jan;5(1):e1000349. doi: 10.1371/journal.pgen.1000349. Epub 2009 Jan 23. 19165336 (Full Text)

A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13.
Kohlsdorf T, Cummings MP, Lynch VJ, Stopper GF, Takahashi K, Wagner GP
(2008 Dec) J Mol Evol. 2008 Dec;67(6):581-93. doi: 10.1007/s00239-008-9156-7. 18855040

Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals.
Lynch VJ, Tanzer A, Wang Y, Leung FC, Gellersen B, Emera D, Wagner GP
(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 (Full Text)

Resurrecting the role of transcription factor change in developmental evolution.
Lynch VJ, Wagner GP
(2008 Sep) Evolution. 2008 Sep;62(9):2131-54. doi: 10.1111/j.1558-5646.2008.00440.x. Epub 2008 Jun 28. 18564379

The gene regulatory logic of transcription factor evolution.
Wagner GP, Lynch VJ
(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.
Lynch VJ
(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.
Lynch VJ
(2007 Jan) BMC Evol Biol. 2007 Jan 18;7:2. 17233905 (Full Text)

Adaptive evolution of Hox-gene homeodomains after cluster duplications.
Lynch VJ, Roth JJ, Wagner GP
(2006 Nov) BMC Evol Biol. 2006 Nov 1;6:86. 17078881 (Full Text)

The "fish-specific" Hox cluster duplication is coincident with the origin of teleosts.
Crow KD, Stadler PF, Lynch VJ, Amemiya C, Wagner GP
(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.
Wagner GP, Lynch VJ
(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.
Lynch VJ, Roth JJ, Takahashi K, Dunn CW, Nonaka DF, Stopper GF, Wagner GP
(2004 Nov) Proc Biol Sci. 2004 Nov 7;271(1554):2201-7. 15539344 (Full Text)