Gene Loss

Publication Details

Identifier: JB_DRJTNG

Curator: M. Lopes-Marques

Title:

Losses of human disease-associated genes in placental mammals.

Abstract:

We systematically investigate whether losses of human disease-associated genes occurred in other mammals during evolution. We first show that genes lost in any of 62 non-human mammals generally have a lower degree of pleiotropy, and are highly depleted in essential and disease-associated genes. Despite this under-representation, we discovered multiple genes implicated in human disease that are truly lost in non-human mammals. In most cases, traits resembling human disease symptoms are present but not deleterious in gene-loss species, exemplified by losses of genes causing human eye or teeth disorders in poor-vision or enamel-less mammals. We also found widespread losses of PCSK9 and CETP genes, where loss-of-function mutations in humans protect from atherosclerosis. Unexpectedly, we discovered losses of disease genes (TYMP, TBX22, ABCG5, ABCG8, MEFV, CTSE) where deleterious phenotypes do not manifest in the respective species. A remarkable example is the uric acid-degrading enzyme UOX, which we found to be inactivated in elephants and manatees. While UOX loss in hominoids led to high serum uric acid levels and a predisposition for gout, elephants and manatees exhibit low uric acid levels, suggesting alternative ways of metabolizing uric acid. Together, our results highlight numerous mammals that are 'natural knockouts' of human disease genes.

Last update:

29-06-2024

Associated Glosses (100 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_QJTACR	Ailuropoda melanoleuca	TYMP	LOF (frameshift, premature stop, ss)	Full	Carnivora	10.1093/nargab/lqz012
GL_RI1FP5	Pteropus alecto	PCSK9	Exon(s) deletion	Full	Chiroptera	10.1093/nargab/lqz012
GL_RJLGOW	Capra hircus	PCSK9	Exon(s) deletion	Full	No	10.1093/nargab/lqz012
GL_RNYFYV	Leptonychotes weddellii	CETP	Exon(s) deletion	Full	Laurasiatheria	10.1093/nargab/lqz012
GL_RTYXHS	Elephas maximus indicus	ABCG5	LOF (frameshift, premature stop, ss)	Full	Elephantidae	10.1093/nargab/lqz012
GL_RVJCSB	Trichechus manatus latirostris	Uox	LOF (frameshift, premature stop, ss)	Full		10.1093/nargab/lqz012
GL_S2LI1H	Mustela putorius furo	PCSK9	Gene deletion	Full	Carnivora	10.1093/nargab/lqz012
GL_SA1JZE	Felis catus	TYMP	LOF (frameshift, premature stop, ss)	Full	Carnivora	10.1093/nargab/lqz012
GL_SBRDQN	Cavia porcellus	TBX22	Gene deletion	Full	No	10.1093/nargab/lqz012
GL_SWQSTL	Vicugna pacos	TYMP	LOF (frameshift, premature stop, ss)	Full	Artiodactyla	10.1093/nargab/lqz012