Patterns of variation in cis-regulatory regions: examining evidence of purifying selection
Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical sig...
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| Published in | BMC genomics Vol. 19; no. 1; pp. 95 - 14 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central
26.01.2018
BioMed Central Ltd BMC |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1471-2164 1471-2164 |
| DOI | 10.1186/s12864-017-4422-y |
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| Abstract | Background
With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.
Results
We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.
Conclusions
In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. |
|---|---|
| AbstractList | Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. Results We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. Conclusions In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. Keywords: Regulatory regions, Purifying selection, Selection efficacy, Non-coding DNA, Functional elements, Population genetics With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.BACKGROUNDWith only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.RESULTSWe disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements.CONCLUSIONSIn order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. Abstract Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. Results We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. Conclusions In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. Background: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. Results: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. Conclusions: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements. Results We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations. Conclusions In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements. |
| ArticleNumber | 95 |
| Audience | Academic |
| Author | Naidoo, Thijessen Sjödin, Per Schlebusch, Carina Jakobsson, Mattias |
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| Cites_doi | 10.1126/science.1058040 10.1038/nrg2538 10.1126/science.1235587 10.1093/genetics/134.4.1289 10.1126/science.1227721 10.1098/rspb.2009.1473 10.1126/science.1181498 10.1128/MCB.16.6.2802 10.1126/science.1098119 10.1093/genetics/123.3.585 10.1186/gb-2012-13-9-r48 10.1017/S0016672300014634 10.1126/science.1198878 10.1093/genetics/141.4.1605 10.1093/nar/gks1284 10.1093/gbe/evt028 10.1126/science.1225057 10.1093/genetics/155.3.1405 10.1073/pnas.83.5.1359 10.1093/nar/20.12.3191 10.1111/mec.12524 10.1016/0092-8674(83)90015-6 10.1093/bioinformatics/btq033 10.1073/pnas.0502300102 10.1093/bioinformatics/bts277 10.1016/j.cell.2009.06.001 10.1111/j.1365-294X.2011.05308.x 10.1038/nature05295 10.1093/nar/gkr342 10.1038/nmeth.1937 10.1073/pnas.1318948111 10.1101/gr.146506.112 10.1098/rstb.2016.0471 10.1007/s00018-012-0990-9 10.1016/0092-8674(85)90057-1 10.1101/gr.772403 10.1016/j.cell.2011.11.058 10.1128/MCB.22.11.3820-3831.2002 10.1101/gr.098921.109 10.1038/nature15393 10.1093/oxfordjournals.molbev.a025634 10.1016/j.tig.2014.02.002 10.1214/aos/1176347265 10.1093/nar/5.9.3157 10.1038/ng.3186 10.1038/35057062 10.1023/A:1008800423698 10.1146/annurev.ge.15.120181.001405 10.1093/genetics/105.2.437 10.1105/tpc.107.057190 10.1093/database/bau062 10.1101/gr.5573107 10.1038/nature11247 10.1016/j.ajhg.2014.09.006 10.1146/annurev.genet.39.073003.112420 10.1093/nar/gkv1194 |
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| Keywords | Functional elements Regulatory regions Non-coding DNA Selection efficacy Population genetics Purifying selection |
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| References | JA Stamatoyannopoulos (4422_CR12) 2012; 22 FMTA Busing (4422_CR62) 1999; 9 PD Thomas (4422_CR57) 2003; 13 J Wakeley (4422_CR63) 2010 DS Lawrie (4422_CR17) 2014; 30 DJ Galas (4422_CR29) 1978; 5 RE Thurman (4422_CR30) 2012; 489 DM Rand (4422_CR66) 1996; 13 YB Simons (4422_CR36) 2014; 46 4422_CR52 F Tajima (4422_CR59) 1983; 105 LD Ward (4422_CR16) 2012; 337 MB Gerstein (4422_CR54) 2012; 489 ENCODE Project Consortium (4422_CR7) 2012; 489 D Thorburn (4422_CR65) 1977; 4 R Sabarinathan (4422_CR48) 2016; 532 D Shortle (4422_CR1) 1981; 15 M XJ (4422_CR19) 2011; 39 4422_CR15 4422_CR14 JC Venter (4422_CR3) 2001; 291 AR Quinlan (4422_CR55) 2010; 26 W Fu (4422_CR35) 2014; 95 S Peischl (4422_CR33) 2013; 22 GN Filippova (4422_CR46) 1996; 16 WC Forrester (4422_CR6) 1986; 83 JE Phillips (4422_CR45) 2009; 137 M Kellis (4422_CR9) 2014; 111 Y Cheng (4422_CR8) 2009; 19 G Bejerano (4422_CR13) 2004; 304 RD Hernandez (4422_CR25) 2011; 331 B Charlesworth (4422_CR23) 1993; 134 J Li (4422_CR21) 2012; 21 R Do (4422_CR34) 2015; 47 ES Lander (4422_CR2) 2001; 409 K Lindblad-Toh (4422_CR10) 2011; 478 D Graur (4422_CR11) 2013; 5 F Tajima (4422_CR60) 1989; 123 4422_CR64 W Amos (4422_CR27) 2010; 277 R Drmanac (4422_CR50) 2010; 327 H Mi (4422_CR58) 2016; 44 MM Hoffman (4422_CR44) 2012; 9 JJ Jonsson (4422_CR40) 1992; 20 SH Williamson (4422_CR22) 2005; 102 BS Weir (4422_CR53) 1984; 38 R Nielsen (4422_CR32) 2005; 39 AB Rose (4422_CR41) 2008; 20 S Neph (4422_CR67) 2012; 28 CM Farrell (4422_CR47) 2002; 22 J Wakeley (4422_CR28) 2009 E Khurana (4422_CR20) 2013; 342 JM Smith (4422_CR37) 1974; 23 RR Hudson (4422_CR24) 1995; 141 A Auton (4422_CR51) 2015; 526 LW Barrett (4422_CR39) 2012; 69 BM Emerson (4422_CR5) 1985; 41 J Banerji (4422_CR4) 1983; 33 MM Hoffman (4422_CR42) 2013; 41 HR Kunsch (4422_CR61) 1989; 17 CM Schlebusch (4422_CR26) 2012; 338 ZD Zhang (4422_CR31) 2007; 17 4422_CR38 J Ernst (4422_CR43) 2012; 9 JM Vaquerizas (4422_CR56) 2009; 10 JC Fay (4422_CR49) 2000; 155 D Schmidt (4422_CR18) 2012; 148 |
| References_xml | – volume: 291 start-page: 1304 year: 2001 ident: 4422_CR3 publication-title: Science doi: 10.1126/science.1058040 – start-page: 119 volume-title: Evol since Darwin first 150 years. Sunderland, MA: Sinauer and associates year: 2010 ident: 4422_CR63 – volume: 10 start-page: 252 year: 2009 ident: 4422_CR56 publication-title: Nat Rev Genet doi: 10.1038/nrg2538 – volume: 4 start-page: 113 year: 1977 ident: 4422_CR65 publication-title: Scand J Stat – volume: 342 start-page: 1235587 year: 2013 ident: 4422_CR20 publication-title: Science doi: 10.1126/science.1235587 – volume: 38 start-page: 1358 year: 1984 ident: 4422_CR53 publication-title: Evolution (N Y) – volume: 134 start-page: 1289 year: 1993 ident: 4422_CR23 publication-title: Genetics doi: 10.1093/genetics/134.4.1289 – volume: 338 start-page: 374 year: 2012 ident: 4422_CR26 publication-title: Science doi: 10.1126/science.1227721 – volume: 277 start-page: 131 year: 2010 ident: 4422_CR27 publication-title: Proceedings Biol Sci doi: 10.1098/rspb.2009.1473 – volume: 327 start-page: 78 year: 2010 ident: 4422_CR50 publication-title: Science doi: 10.1126/science.1181498 – volume: 16 start-page: 2802 year: 1996 ident: 4422_CR46 publication-title: Mol Cell Biol doi: 10.1128/MCB.16.6.2802 – volume: 9 start-page: 215 year: 2012 ident: 4422_CR43 publication-title: Nat Publ Group – volume: 304 start-page: 1321 year: 2004 ident: 4422_CR13 publication-title: Science doi: 10.1126/science.1098119 – volume: 123 start-page: 585 year: 1989 ident: 4422_CR60 publication-title: Genetics doi: 10.1093/genetics/123.3.585 – volume: 532 start-page: 264 year: 2016 ident: 4422_CR48 publication-title: Nat Publ Group – ident: 4422_CR64 doi: 10.1186/gb-2012-13-9-r48 – volume: 478 start-page: 476 year: 2011 ident: 4422_CR10 publication-title: Nat Publ Group – volume: 23 start-page: 23 year: 1974 ident: 4422_CR37 publication-title: Genet Res doi: 10.1017/S0016672300014634 – volume: 331 start-page: 920 year: 2011 ident: 4422_CR25 publication-title: Science doi: 10.1126/science.1198878 – volume: 141 start-page: 1605 year: 1995 ident: 4422_CR24 publication-title: Genetics doi: 10.1093/genetics/141.4.1605 – volume: 41 start-page: 827 year: 2013 ident: 4422_CR42 publication-title: Nucleic Acids Res doi: 10.1093/nar/gks1284 – volume: 489 start-page: 91 year: 2012 ident: 4422_CR54 publication-title: Nat Publ Group – volume: 5 start-page: 578 year: 2013 ident: 4422_CR11 publication-title: Genome Biol Evol doi: 10.1093/gbe/evt028 – volume: 337 start-page: 1675 year: 2012 ident: 4422_CR16 publication-title: Science doi: 10.1126/science.1225057 – volume: 155 start-page: 1405 year: 2000 ident: 4422_CR49 publication-title: Genetics doi: 10.1093/genetics/155.3.1405 – ident: 4422_CR52 – volume: 83 start-page: 1359 year: 1986 ident: 4422_CR6 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.83.5.1359 – volume: 20 start-page: 3191 year: 1992 ident: 4422_CR40 publication-title: Nucleic Acids Res doi: 10.1093/nar/20.12.3191 – volume: 22 start-page: 5972 year: 2013 ident: 4422_CR33 publication-title: Mol Ecol doi: 10.1111/mec.12524 – volume: 33 start-page: 729 year: 1983 ident: 4422_CR4 publication-title: Cell doi: 10.1016/0092-8674(83)90015-6 – volume: 26 start-page: 841 year: 2010 ident: 4422_CR55 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq033 – volume: 102 start-page: 7882 year: 2005 ident: 4422_CR22 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0502300102 – volume: 28 start-page: 1919 year: 2012 ident: 4422_CR67 publication-title: Bioinformatics doi: 10.1093/bioinformatics/bts277 – volume: 137 start-page: 1194 year: 2009 ident: 4422_CR45 publication-title: Cell doi: 10.1016/j.cell.2009.06.001 – volume: 21 start-page: 28 year: 2012 ident: 4422_CR21 publication-title: Mol Ecol doi: 10.1111/j.1365-294X.2011.05308.x – ident: 4422_CR14 doi: 10.1038/nature05295 – volume: 39 start-page: 7058 year: 2011 ident: 4422_CR19 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkr342 – volume: 9 start-page: 473 year: 2012 ident: 4422_CR44 publication-title: Nat Methods doi: 10.1038/nmeth.1937 – volume: 111 start-page: 6131 year: 2014 ident: 4422_CR9 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1318948111 – volume: 22 start-page: 1602 year: 2012 ident: 4422_CR12 publication-title: Genome Res doi: 10.1101/gr.146506.112 – ident: 4422_CR38 doi: 10.1098/rstb.2016.0471 – volume: 69 start-page: 3613 year: 2012 ident: 4422_CR39 publication-title: Cell Mol Life Sci doi: 10.1007/s00018-012-0990-9 – volume: 41 start-page: 21 year: 1985 ident: 4422_CR5 publication-title: Cell doi: 10.1016/0092-8674(85)90057-1 – volume: 13 start-page: 2129 year: 2003 ident: 4422_CR57 publication-title: Genome Res doi: 10.1101/gr.772403 – volume: 148 start-page: 335 year: 2012 ident: 4422_CR18 publication-title: Cell doi: 10.1016/j.cell.2011.11.058 – volume-title: Coalescent theory: an introduction year: 2009 ident: 4422_CR28 – volume: 22 start-page: 3820 year: 2002 ident: 4422_CR47 publication-title: Mol Cell Biol doi: 10.1128/MCB.22.11.3820-3831.2002 – volume: 19 start-page: 2172 year: 2009 ident: 4422_CR8 publication-title: Genome Res doi: 10.1101/gr.098921.109 – volume: 526 start-page: 68 year: 2015 ident: 4422_CR51 publication-title: Nature doi: 10.1038/nature15393 – volume: 13 start-page: 735 year: 1996 ident: 4422_CR66 publication-title: Mol Biol Evol doi: 10.1093/oxfordjournals.molbev.a025634 – volume: 30 start-page: 133 year: 2014 ident: 4422_CR17 publication-title: Trends Genet Elsevier Ltd doi: 10.1016/j.tig.2014.02.002 – volume: 489 start-page: 75 year: 2012 ident: 4422_CR30 publication-title: Nat Publ Group – volume: 46 start-page: 220 year: 2014 ident: 4422_CR36 publication-title: Nat Publ Group – volume: 17 start-page: 1217 year: 1989 ident: 4422_CR61 publication-title: Ann Stat doi: 10.1214/aos/1176347265 – volume: 5 start-page: 3157 year: 1978 ident: 4422_CR29 publication-title: Nucleic Acids Res doi: 10.1093/nar/5.9.3157 – volume: 47 start-page: 126 year: 2015 ident: 4422_CR34 publication-title: Nat Genet doi: 10.1038/ng.3186 – volume: 409 start-page: 860 year: 2001 ident: 4422_CR2 publication-title: Nature doi: 10.1038/35057062 – volume: 9 start-page: 3 year: 1999 ident: 4422_CR62 publication-title: Stat Comput doi: 10.1023/A:1008800423698 – volume: 15 start-page: 265 year: 1981 ident: 4422_CR1 publication-title: Annu Rev Genet doi: 10.1146/annurev.ge.15.120181.001405 – volume: 105 start-page: 437 year: 1983 ident: 4422_CR59 publication-title: Genetics doi: 10.1093/genetics/105.2.437 – volume: 20 start-page: 543 year: 2008 ident: 4422_CR41 publication-title: Plant Cell doi: 10.1105/tpc.107.057190 – ident: 4422_CR15 doi: 10.1093/database/bau062 – volume: 17 start-page: 787 year: 2007 ident: 4422_CR31 publication-title: Genome Res doi: 10.1101/gr.5573107 – volume: 489 start-page: 57 year: 2012 ident: 4422_CR7 publication-title: Nature doi: 10.1038/nature11247 – volume: 95 start-page: 421 year: 2014 ident: 4422_CR35 publication-title: Hum Genet doi: 10.1016/j.ajhg.2014.09.006 – volume: 39 start-page: 197 year: 2005 ident: 4422_CR32 publication-title: Annu Rev Genet doi: 10.1146/annurev.genet.39.073003.112420 – volume: 44 start-page: D336 year: 2016 ident: 4422_CR58 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkv1194 |
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With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much... With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has... Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much... Background: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much... Abstract Background With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of... |
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| SubjectTerms | Animal Genetics and Genomics Biomedical and Life Sciences Comparative and evolutionary genomics Functional elements Genetic research Genetic variation Life Sciences Microarrays Microbial Genetics and Genomics Non-coding DNA Plant Genetics and Genomics Population genetics Proteomics Purifying selection Regulatory regions Research Article Selection efficacy Testing |
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| Title | Patterns of variation in cis-regulatory regions: examining evidence of purifying selection |
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