Adaptive Evolution and Frequent Gene Conversion in the Brain Expressed X-Linked Gene Family in Mammals

TM2 domain containing (TM2D) proteins are conserved in metazoans and encoded by three separate genes in each species. Rare variants in TM2D3 are associated with Alzheimer's disease (AD) and its fly ortholog almondex is required for embryonic Notch signaling. However, the functions of this gene family remain elusive. We knocked-out all three TM2D genes (almondex, CG11103/amaretto, CG10795/biscotti) in Drosophila and found that they share the same maternal-effect neurogenic defect. Triple null animals are not phenotypically worse than single nulls, suggesting these genes function together. Overexpression of the most conserved region of the TM2D proteins acts as a potent inhibitor of Notch signaling at the γ-secretase cleavage step. Lastly, Almondex is detected in the brain and its loss causes shortened lifespan accompanied by progressive electrophysiological defects. The functional links between all three TM2D genes are likely to be evolutionarily conserved, suggesting that this entire gene family may be involved in AD.

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Gene Conversion and Functional Divergence in the ?-Globin Gene Family

Journal of Molecular Evolution ◽

10.1007/s00239-004-2612-0 ◽

2004 ◽

Vol 59 (2) ◽

pp. 177-189 ◽

Cited By ~ 25

Author(s):

Gabriela Aguileta ◽

Joseph P. Bielawski ◽

Ziheng Yang

Keyword(s):

Gene Family ◽

Gene Conversion ◽

Functional Divergence ◽

Globin Gene

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Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution

BMC Evolutionary Biology ◽

10.1186/1471-2148-11-149 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 41

Author(s):

Yinhua Huang ◽

Nicholas D Temperley ◽

Liming Ren ◽

Jacqueline Smith ◽

Ning Li ◽

...

Keyword(s):

Molecular Evolution ◽

Gene Duplication ◽

Positive Selection ◽

Gene Family ◽

Gene Conversion ◽

History Of

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Analysis of a novel VHS107 haplotype in CLA-2 and WSA mice. Evidence for gene conversion among IgVH genes in outbred populations.

Journal of Experimental Medicine ◽

10.1084/jem.170.6.1811 ◽

1989 ◽

Vol 170 (6) ◽

pp. 1811-1823 ◽

Cited By ~ 7

Author(s):

S E Ferguson ◽

M P Cancro ◽

B A Osborne

Keyword(s):

Gene Family ◽

Gene Conversion ◽

Heavy Chain ◽

Cdna Sequence ◽

The Other ◽

Base Substitution ◽

Feral Population ◽

Allelic Differences ◽

Outbred Populations

Gene conversion has been suggested as the basis for many VH allelic differences, particularly in the murine VHS107 family. Whether conversion among IgVH genes is likely to have occurred in outbred populations has not been directly addressed. The CLA-2/Cn and WSA strains, which were recently and independently derived from a feral population exhibiting low responsiveness to PC, provide the opportunity to approach this question. In previous studies, the heavy chain cDNA sequence of a PC-specific hybridoma derived from CLA-2/Cn suggested gene conversion events within the VHS107 family. Accordingly, we have examined the germline VHS107 genes of CLA-2/Cn and WSA. The results indicate that: (a) The CLA-2 and WSA strains bear an identical but novel VHS107 family haplotype, which lacks a V3 element and contains a V1, a V13, and two V11 genes; (b) low PC responsiveness in these populations is unlikely due to an inability to express the V1 member of the VHS107 gene family; and (c) when compared with the other known VHS107 haplotypes, the proportion of differences consistent with gene conversion greatly exceeds that expected by random base substitution. Thus, gene conversion events appear to have occurred with considerable frequency in the evolution of the murine VHS107 family, especially among the V3, V13, and V11 members.

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HIGH FREQUENCY OF 3:1 TETRAD RATIOS FOR THE PDX-1 LOCUS OF NEUROSPORA CRASSA

Canadian Journal of Genetics and Cytology ◽

10.1139/g69-007 ◽

1969 ◽

Vol 11 (1) ◽

pp. 60-64 ◽

Cited By ~ 1

Author(s):

A. Radford ◽

S. F. H. Threlkeld

Keyword(s):

Neurospora Crassa ◽

Gene Conversion ◽

High Frequency ◽

High Ratio ◽

The Other ◽

Linked Gene

Nine crosses, involving three alleles, were used in a study of recombination at the pdx-1 locus of Neurospora. In two of the crosses, an unusually high ratio of apparent gene conversion was observed, Two asci of the aberrant type were analyzed by means of prototrophs from backcrosses. In one case the ascus was confirmed as an example of genuine gene conversion. In the other, however, the original scoring of the ascus was found to be due to the presence of a closely linked gene capable of modifying the expression of the two conditional pdx-1 mutants used in the study.

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