Antagonistic maternal and direct effects of the leptin receptor gene on body weight in pigs

Abstract

Maternal effects on offspring growth can impact survival and evolution of natural and domesticated populations. Genetic correlation estimates often support a negative relationship between direct and maternal effects. However, the genetic underpinnings whereby this antagonism operates are unclear. In pigs, sow feeding status and body composition condition piglet development and growth. We hypothesized that variants in genes impacting these traits may be causative of maternal influences that could be antagonistic to the direct effects for piglet growth. A recessive missense mutation (C>T) in the porcine leptin receptor (LEPR) gene (rs709596309) has been identified as the possible causal polymorphism for increased feed intake and fatness. Using data from a Duroc line, we show that the TT sows exerted a negative impact on the body weight of their offspring at the end of the growing period of similar extent to the positive direct effect of the TT genotype over each individual. Thus, TT pigs from TT dams were about as heavy as CC and CT (C–) pigs from C–dams, but TT pigs from C–dams were around 5% heavier than C–pigs from TT dams. In contrast, body composition was only influenced by LEPR direct effects. This antagonism is due to a higher propensity of TT pigs for self-maintenance rather than for offspring investment. We show that TT pigs consumed more feed, favored fatty acid uptake over release, and produced lighter piglets at weaning than their C–counterparts. We conclude that LEPR underlies a transgenerational mechanism for energy distribution that allocates resources to the sow or the offspring according to whether selective pressure is exerted before or after weaning.

Heritability and genetic correlation estimates of semen production traits with litter traits and pork production traits in purebred Duroc pigs

“…Previous studies estimated a weak genetic correlation between litter size traits and pork production traits in pigs ( Ducos and Bidanel, 1996 ; Misumi et al, 2009 ; Ogawa et al, 2020 ). Solé et al (2021a , 2021b ) investigated the effects of two single nucleotide polymorphisms ( SNPs ), rs709596309 C>T of the leptin receptor ( LEPR ) gene and rs80912566 T>C of the stearoyl-CoA desaturase ( SCD ) gene, on piglet weight at weaning in Duroc pigs. The SNP of LEPR is thought to affect BF in Duroc pigs ( Óvilo et al, 2005 ; Uemoto et al, 2012 ; Ros-Freixedes et al, 2016 ), and may be in part responsible for the negative genetic correlation between BF and MWW here (−0.56).…”

Genetic architecture and major genes for backfat thickness in pig lines of diverse genetic backgrounds

“…Previous studies have estimated that dominance effects account for 4 to 15% of the phenotypic variance, and imprinting effects for 1 to 3% [ 30 , 31 ]. Indeed, major genes such as LEPR and IGF2 have been reported to have dominance [ 19 , 34 ] and imprinting [ 8 ] effects, respectively, on backfat thickness. While non-additive effects may be of interest for understanding genetic or physiological mechanisms, they have limited applications in breeding practices [ 35 ].…”

“…We only found one significant SNP near this gene in one of the eight lines, on SSC6 at 147.5 Mb, which is only 0.6 Mb from the LEPR gene at 146.8–146.9 Mb. Non-significance of this region in the other lines could be the result of intense selection for feed efficiency in the studied lines [ 34 ]. A study on signatures of selection in a Duroc line that was selected for increased intramuscular fat content, with a correlated response for backfat thickness, revealed greater extended haplotype homozygosity in this region compared to a control line [ 45 ].…”

Genome-wide analyses reveal a strong association between LEPR gene variants and body fat reserves in ewes

“…2012; R os-Freixedes et al . 2016) and antagonistic maternal and direct effects on body weight (S ole et al . 2021).…”

“…Various mutations in the LEPR gene leading to leptin signaling deficiency through disruption in the LEPR function resulted in many cases in obesity/diabetes phenotypes in humans and rodents (CHAGNON et al 1999;YIANNAKOURIS et al 2001;ISRAEL AND CHUA 2010;GHALANDARI et al 2015;BERGER AND KLÖTING 2021). In pigs, a missense mutation in the LEPR gene was also associated with higher fatness levels (UEMOTO et al 2012;ROS-FREIXEDES et al 2016) and antagonistic maternal and direct effects on body weight (SOLE et al 2021). In sheep, in addition to the effect on reproductive traits, Haldar et al (HALDAR et al 2014) also found an effect of the LEPR p.P1019S mutation on adult body weight, with ewes with the mutation being heavier than the other ewes.…”