Craig Lowe

Positions:

Assistant Professor of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2010

University of California - Santa Cruz

Grants:

From a Long List to Causal Variants: High-Throughput Gene Regulatory Assays in Developing Tissues

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

From a Long List to Causal Variants: High-Throughput Gene Regulatory Assays in Developing Tissues

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Corrigendum: Detecting differential copy number variation between groups of samples.

Authors
Lowe, CB; Sanchez-Luege, N; Howes, TR; Brady, SD; Daugherty, RR; Jones, FC; Bell, MA; Kingsley, DM
MLA Citation
Lowe, Craig B., et al. “Corrigendum: Detecting differential copy number variation between groups of samples.Genome Res, vol. 28, no. 5, May 2018, p. 766.1. Pubmed, doi:10.1101/gr.237370.118.
URI
https://scholars.duke.edu/individual/pub1427154
PMID
29717001
Source
pubmed
Published In
Genome Res
Volume
28
Published Date
Start Page
766.1
DOI
10.1101/gr.237370.118

Comparative genomics search for losses of long-established genes on the human lineage.

Taking advantage of the complete genome sequences of several mammals, we developed a novel method to detect losses of well-established genes in the human genome through syntenic mapping of gene structures between the human, mouse, and dog genomes. Unlike most previous genomic methods for pseudogene identification, this analysis is able to differentiate losses of well-established genes from pseudogenes formed shortly after segmental duplication or generated via retrotransposition. Therefore, it enables us to find genes that were inactivated long after their birth, which were likely to have evolved nonredundant biological functions before being inactivated. The method was used to look for gene losses along the human lineage during the approximately 75 million years (My) since the common ancestor of primates and rodents (the euarchontoglire crown group). We identified 26 losses of well-established genes in the human genome that were all lost at least 50 My after their birth. Many of them were previously characterized pseudogenes in the human genome, such as GULO and UOX. Our methodology is highly effective at identifying losses of single-copy genes of ancient origin, allowing us to find a few well-known pseudogenes in the human genome missed by previous high-throughput genome-wide studies. In addition to confirming previously known gene losses, we identified 16 previously uncharacterized human pseudogenes that are definitive losses of long-established genes. Among them is ACYL3, an ancient enzyme present in archaea, bacteria, and eukaryotes, but lost approximately 6 to 8 Mya in the ancestor of humans and chimps. Although losses of well-established genes do not equate to adaptive gene losses, they are a useful proxy to use when searching for such genetic changes. This is especially true for adaptive losses that occurred more than 250,000 years ago, since any genetic evidence of the selective sweep indicative of such an event has been erased.
Authors
Zhu, J; Sanborn, JZ; Diekhans, M; Lowe, CB; Pringle, TH; Haussler, D
MLA Citation
Zhu, Jingchun, et al. “Comparative genomics search for losses of long-established genes on the human lineage.Plos Comput Biol, vol. 3, no. 12, Dec. 2007, p. e247. Pubmed, doi:10.1371/journal.pcbi.0030247.
URI
https://scholars.duke.edu/individual/pub1348811
PMID
18085818
Source
pubmed
Published In
Plos Computational Biology
Volume
3
Published Date
Start Page
e247
DOI
10.1371/journal.pcbi.0030247

Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53.

The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably the transcriptional network of human tumor suppressor protein p53. A total of 1,509 of approximately 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site. The LTR10 and MER61 families are particularly enriched for copies with a p53 site. These ERV families are primate-specific and transposed actively near the time when the New World and Old World monkey lineages split. Other mammalian species lack these p53 response elements. Analysis of published genomewide ChIP data for p53 indicates that more than one-third of identified p53 binding sites are accounted for by ERV copies with a p53 site. ChIP and expression studies for individual genes indicate that human ERV p53 sites are likely part of the p53 transcriptional program and direct regulation of p53 target genes. These results demonstrate how retroelements can significantly shape the regulatory network of a transcription factor in a species-specific manner.
Authors
Wang, T; Zeng, J; Lowe, CB; Sellers, RG; Salama, SR; Yang, M; Burgess, SM; Brachmann, RK; Haussler, D
MLA Citation
Wang, Ting, et al. “Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53.Proc Natl Acad Sci U S A, vol. 104, no. 47, Nov. 2007, pp. 18613–18. Pubmed, doi:10.1073/pnas.0703637104.
URI
https://scholars.duke.edu/individual/pub1348816
PMID
18003932
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
104
Published Date
Start Page
18613
End Page
18618
DOI
10.1073/pnas.0703637104

Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.

At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Recent work has highlighted a handful of cases where mobile element insertions have resulted in the introduction of novel conserved nonexonic elements. Here, we present a genome-wide survey of 10,402 constrained nonexonic elements in the human genome that have all been deposited by characterized mobile elements. These repeat instances have been under strong purifying selection since at least the boreoeutherian ancestor (100 Mya). They are most often located in gene deserts and show a strong preference for residing closest to genes involved in development and transcription regulation. In particular, constrained nonexonic elements with clear repetitive origins are located near genes involved in cell adhesion, including all characterized cellular members of the reelin-signaling pathway. Overall, we find that mobile elements have contributed at least 5.5% of all constrained nonexonic elements unique to mammals, suggesting that mobile elements may have played a larger role than previously recognized in shaping and specializing the landscape of gene regulation during mammalian evolution.
Authors
Lowe, CB; Bejerano, G; Haussler, D
MLA Citation
Lowe, Craig B., et al. “Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.Proc Natl Acad Sci U S A, vol. 104, no. 19, May 2007, pp. 8005–10. Pubmed, doi:10.1073/pnas.0611223104.
URI
https://scholars.duke.edu/individual/pub1348815
PMID
17463089
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of the United States of America
Volume
104
Published Date
Start Page
8005
End Page
8010
DOI
10.1073/pnas.0611223104

A distal enhancer and an ultraconserved exon are derived from a novel retroposon.

Hundreds of highly conserved distal cis-regulatory elements have been characterized so far in vertebrate genomes. Many thousands more are predicted on the basis of comparative genomics. However, in stark contrast to the genes that they regulate, in invertebrates virtually none of these regions can be traced by using sequence similarity, leaving their evolutionary origins obscure. Here we show that a class of conserved, primarily non-coding regions in tetrapods originated from a previously unknown short interspersed repetitive element (SINE) retroposon family that was active in the Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in the Silurian period at least 410 million years ago (ref. 4), and seems to be recently active in the 'living fossil' Indonesian coelacanth, Latimeria menadoensis. Using a mouse enhancer assay we show that one copy, 0.5 million bases from the neuro-developmental gene ISL1, is an enhancer that recapitulates multiple aspects of Isl1 expression patterns. Several other copies represent new, possibly regulatory, alternatively spliced exons in the middle of pre-existing Sarcopterygian genes. One of these, a more than 200-base-pair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of the messenger RNA processing gene PCBP2 (ref. 6). These add to a growing list of examples in which relics of transposable elements have acquired a function that serves their host, a process termed 'exaptation', and provide an origin for at least some of the many highly conserved vertebrate-specific genomic sequences.
Authors
Bejerano, G; Lowe, CB; Ahituv, N; King, B; Siepel, A; Salama, SR; Rubin, EM; Kent, WJ; Haussler, D
MLA Citation
Bejerano, Gill, et al. “A distal enhancer and an ultraconserved exon are derived from a novel retroposon.Nature, vol. 441, no. 7089, May 2006, pp. 87–90. Pubmed, doi:10.1038/nature04696.
URI
https://scholars.duke.edu/individual/pub1348812
PMID
16625209
Source
pubmed
Published In
Nature
Volume
441
Published Date
Start Page
87
End Page
90
DOI
10.1038/nature04696