. 2021 May 22;38(10):4268–4285. doi: 10.1093/molbev/msab156

Table 2.

Genes Detected by Both XPEHH and Fst in Relation to Environmental Adaptations.

Genes and Sweep Regions	Relevant Biological Functions for the Candidate Genes
*Adaptation to high altitude stresses (hypoxia, thrombosis, and cold tolerance) (Low minTemp)*
Chr5:17230000 − 17290000^a^,^b Gene cluster: CLP1, YPEL4, ENSGALG00000007381, UBEL6, TIMM10, RTN4RL2, SLC43A3, PGR2/3, P2RX3	CLP1—linked to cardiovascular function and cardiac muscle hypertrophy (Espinoza-Derout et al. 2007); YPEL4—role in pulmonary diseases (Truong et al. 2018); P2RX3—blood coagulation, responses to cold, heat and hypoxia (Uniprot); ENSGALG00000007381—blood coagulation (Reactome); SLC43A3—roles in lung tissue repair and growth under oxidative stress (Furukawa et al. 2015); PGR2/3—immune response (Uniprot); RTN4RL2—roles in axon regeneration and protection of motoneurons against apoptosis (Uniprot), and upregulated in myopathy-affected condition in broiler possibly in response to hypoxia (Marchesi et al. 2019); UBE2L6: involved in protein ubiquitination pathway (Uniprot) ; TIMM10—imports transmembrane proteins into the mitochondrial inner membrane (Uniprot); downregulated in hypoxic cells (Lai et al. 2016).
Chr18:5090000 − 5190000^a^,^b UTP18	UTP18—RNA binding and involved in pre-18S rRNA processing (Uniprot); belongs to a gene-network targeted by microRNAs differentially expressed in human hypoxic cardiomyocytes cell line (Lee et al. 2018)
*Water scarcity adaptation (Low precDQ)*
Chr3:71840000 − 73950000^a^,^b (consists of several SRs) Gene cluster: ENSGALG00000036204 , ENSGALG00000025686, MANEA, EPHA7	ENSGALG00000036204—a lncRNA with possible cis-regulatory role on nearby genes; for example, the nearest gene is MMS22L with role in DNA damage repair process (Uniprot); ENSGALG00000025686—U6 spliceosomal RNA with possible role in post-transcriptional modification; MANEA—associated with panic disorder (Jensen et al. 2014); EPHA7—involved in many functions, for example, apoptotic process, axon guidance, brain development, ephrin receptor signaling pathway, and nephric duct morphogenesis (Uniprot)
Chr3:106430000 − 106510000^a^,^b MSRA	MSRA -Cellular protein modification, protein repair, response to oxidative stress (Uniprot).
Chr4:74170000 − 74300000^a^,^b Gene cluster: ENSGALG00000048521, ENSGALG00000050078, ENSGALG00000046053	These lncRNA genes possibly have cis-regulatory functions on nearby genes; a plausible nearby target is PPARGC1A, which is involved in many biological functions.
Chr6:25040000 − 25070000^a^,^b SLK	SLK—mediates apoptosis (Uniprot)
Chr11:18110000 − 18130000^a^,^b BANP	Multicellular organism development, transcriptional regulation, regulation of signal transduction (Uniprot)
*Adaptation to high precipitation seasonality: possible adaptation to water scarcity*
Chr4:2730000 − 2750000^a^,^b HTR2C	Many functions, for example, behavioral fear response, regulation of appetite, regulation of corticotropin-releasing hormone secretion and nervous system processes (Uniprot).
Chr4:74280000 − 74310000^a^,^b ENSGALG00000051573	A lncRNA with possible cis-regulatory functions; the nearest protein coding gene is ENSGALG00000040208
*Possible adaptation to excess rainfall and humidity (Low precSeasonality)*
Chr2:114000000_114100000^a^,^b ENSGALG00000053888	A lncRNA with possible regulatory functions; the nearest gene, YTHDF3 has role in positive regulation of translation (Uniprot).
Chr7:35360000 − 35400000^a^,^b CACNB4	Calcium transport; ion transport (Uniprot)
**Scavenging adaptation to rich source of insect, worm and plant based food (High SoilOrgC)**
Chr1:197230000 − 197310000^a Gene cluster: HBBA, HBE, HBE1, HBBR, ENSGALG00000052767	HBBA, HBE, HBE1, and HBBR—involved in heme binding, oxygen carrier activity, cellular oxidant detoxification, protein hetero-oligomerization, response to organic cyclic compound (Uniprot). ENSGALG00000052767—novel protein coding
Chr10:6820000 − 6870000^a^,^b Gene cluster: THSD4, ENSGALG00000053176	THSD4—has peptidase activity (Uniprot) with possible association with feed efficiency traits (Yao et al. 2013); ENSGALG00000053176 is a MiRNA with possible role in RNA silencing and post-transcriptional regulation of gene expression.
*Scavenging adaptation to low surplus of crop and grain-based food (Low LandUse)*
Chr1:127750000 − 127980000 Gene cluster: STS, PUDP	STS—Lipid and steroid metabolism (Uniprot); PUDP—Nucleotide metabolic process (Uniprot).
Chr1:128960000_129350000^a^,^b ENSGALG00000052489	Novel protein coding gene
Chr3:34260000 − 34320000^a^,^b Gene cluster: SMYD3, KIF26B	SMYD3—Role in transcriptional regulation as a member of an RNA polymerase complex and in cellular response to dexamthasone stimulus (Uniprot); KIF26B—role in cell signaling (Uniprot).
Chr4:56140000 − 56170000^a NDST4	NDST4—Strong association with low abdominal fat content in chicken (Uniprot).
*Scavenging adaptation to crop and grain rich food (High LandUse)*
Chr4:75690000 − 75810000^a^,^b NCAPG	NCAPG—Cell division, mitotic chromosome condensation (Uniprot).

Note.—Genes present in close proximity on the same chromosome are shown as clusters (in a few cases this involves separate sweep regions).

Regions intersecting with highly significant FLK SNPs (P < 0.01) and showing consistent pattern of allele frequency in each Low and High population.

Regions successfully validated in a new population (i.e., overlapping significant FLK SNP showing consistent pattern of allele frequency with at least 15% difference in allele frequency between Low and High populations in the validation set).