MAMMALIA: The Evolution of Brain-Derived Neurotrophic Factor (BDNF) Reveals Insight into Brain Disorder Vulnerability

# MAMMALIA: The Evolution of Brain-Derived Neurotrophic Factor (BDNF) Reveals Insight into Brain Disorder Vulnerability Alexander G Lucaci1*, Michael J Notaras2*^, Sergei L Kosakovsky Pond1, Maarten van den Buuse3,4,5^ 1 Institute for Genomics and Evolutionary Medicine, Science & Education Research Center, Temple University, Philadelphia, Pennsylvania, USA. 2 Center for Neurogenetics, Brain & Mind Research Institute, Weill Medical College, Cornell University, New York, New York, USA. 3 School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia. 4 College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, Australia. 5 Department of Pharmacology, University of Melbourne, Melbourne, VIC, Australia. *Michael J Notaras & Alexander G Lucaci Contributed equally and share first authorship. ^ Shared corresponding authorship between Michael J Notaras & Maarten ven den Buuse, email mjn2004@med.cornell.edu or m.vandenbuuse@latrobe.edu.au. `Updated on 4.13.2021` ## Abstract ## Introduction ## Methods ### *Data Retrieval* Query NCBI via https://www.ncbi.nlm.nih.gov/kis/ortholog/627/?scope=7776 We filtered by Mammals 152 Species were returned. We downloaded all sequences per gene. (Each gene may have several transcripts). This results in 658 transcripts and 654 proteins downloaded. Full description of the downloads can be found in ```data/BDNF_orthologs.csv ``` ### *Data processing* ```scripts/codons.py ``` was used to get coding sequences from the full transcript and protein file. This results in 625 sequences. (Error report: ) ```analyis/BDNF_codons.fasta``` We renamed the FASTA IDs in this file t omake it easier for downstream processing. ```scripts/rename_codon_msa_for_hyphy.py``` The resulting file used for alignment and all other downstream results is ```BDNF_codons_renamed.fasta``` ### Alignment MACSEv2 with default parameters. ### Phylogenetic Tree Construction IQTREE with default parameters ### Evidence for Recombination ### Phylogentic Tree Visualization ## Results ### Figure 1 -- Phylogenetic Tree 625 transcripts, 152 species ![](https://i.imgur.com/BMSD9La.png) ### Description of Recombinants ### Main -- Alignment free analysis -- BUSTEDS BUSTED with synyonymous rate variation found evidence (LRT, p-value = 0.000 ≤ .05) of gene-wide episodic diversifying selection in the selected test branches of your phylogeny 625 Sequences 488 Sites w3 = 8.07, 1.18% of sites ![](https://i.imgur.com/wMaSbZ1.png) ### Main -- Alignment free analysis -- pool FEL/MEME/PRIME FEL ![](https://i.imgur.com/O1OWWMA.png) FEL Positive sites correspond to 165, 214 for p < 0.05, both show up in MEME. MEME | # | Human-Gene Location | Site (our Alignment) | α | β- | p- | β+ | p+ | LRT | p-value | # branches under selection | MEME LogL | FEL LogL | |---:|:------------|-------:|-----------:|---------------------:|----------------:|---------------------:|----------------:|------:|----------:|-----------------------------:|------------:|-----------:| | 1 | 2 | 32 | 1.22 | 0.21 | 0.93 | 65.5 | 0.07 | 7.62 | 0.01 | 0 | -33.77 | -28 | | 2 | 3 | 33 | 0 | 0 | 0.86 | 83.34 | 0.14 | 6.56 | 0.02 | 1 | -39.38 | -35.89 | | 3 | 4 | 34 | 0.19 | 0.19 | 0.91 | 166.59 | 0.09 | 10.37 | 0 | 0 | -37.89 | -32.74 | | 4 | 7 | 37 | 0 | 0 | 0.85 | 103.7 | 0.15 | 11.86 | 0 | 1 | -46.72 | -40.9 | | 5 | 10 | 40 | 0.65 | 0.65 | 0.91 | 170.86 | 0.09 | 5.49 | 0.03 | 0 | -44.67 | -42.02 | | 6 | 11 | 41 | 0.33 | 0.33 | 0.84 | 25.75 | 0.16 | 7.33 | 0.01 | 0 | -46.65 | -44.53 | | 7 | 20 | 50 | 0 | 0 | 0.83 | 26.75 | 0.17 | 5.67 | 0.03 | 1 | -38.02 | -35.22 | | 8 | 29 | 59 | 0.81 | 0.12 | 0.94 | 45.55 | 0.06 | 5.04 | 0.04 | 0 | -31.11 | -28.82 | | 9 | 34 | 64 | 0.87 | 0.45 | 0.81 | 13.56 | 0.19 | 5.22 | 0.03 | 1 | -64.79 | -62.42 | | 10 | 35 | 65 | 0.09 | 0.06 | 0.78 | 11.24 | 0.22 | 7.45 | 0.01 | 1 | -51.43 | -48.45 | | 11 | 36 | 66 | 0.94 | 0 | 0.76 | 10.95 | 0.24 | 6.47 | 0.02 | 2 | -61.95 | -58.59 | | 12 | 37 | 67 | 0 | 0 | 0.76 | 12 | 0.24 | 9.05 | 0 | 2 | -55.58 | -52.32 | | 13 | 38 | 68 | 0.63 | 0.63 | 0.91 | 27.49 | 0.09 | 6.04 | 0.02 | 1 | -54.24 | -51.96 | | 14 | 46 | 82 | 0.47 | 0 | 0.83 | 10.12 | 0.17 | 4.31 | 0.05 | 4 | -48.62 | -46.15 | | 15 | 48 | 84 | 0 | 0 | 0.88 | 67.16 | 0.12 | 10.48 | 0 | 5 | -64.08 | -58.84 | | 16 | 49 | 85 | 1.34 | 0.28 | 0.93 | 30.63 | 0.07 | 5.96 | 0.02 | 2 | -59.78 | -55.36 | | 17 | 54 | 90 | 1.41 | 0 | 0.93 | 38.8 | 0.07 | 13.52 | 0 | 2 | -60.73 | -50.31 | | 18 | 56 | 92 | 0.29 | 0.03 | 0.92 | 78.78 | 0.08 | 6.07 | 0.02 | 2 | -50.41 | -47.01 | | 19 | 57 | 93 | 1.35 | 0 | 0.93 | 55.4 | 0.07 | 6.86 | 0.01 | 1 | -50.76 | -44.72 | | 20 | 61 | 98 | 0 | 0 | 0.95 | 82.37 | 0.05 | 12.31 | 0 | 0 | -37.21 | -31.49 | | 21 | - | 109 | 0.36 | 0.16 | 0.94 | 2222.29 | 0.06 | 7.89 | 0.01 | 0 | -37.21 | -32.46 | | 22 | - | 112 | 0.42 | 0.15 | 0.92 | 52.7 | 0.08 | 7.05 | 0.01 | 0 | -34.23 | -30.8 | | 23 | 65 | 115 | 1.66 | 0.85 | 0.96 | 104.79 | 0.04 | 8.63 | 0.01 | 1 | -70.82 | -65.64 | | 24 | 67 | 117 | 1.29 | 0 | 0.93 | 75.83 | 0.07 | 7.07 | 0.01 | 1 | -47.75 | -42 | | 25 | 68 | 118 | 1.19 | 0 | 0.88 | 39.93 | 0.12 | 7.05 | 0.01 | 0 | -45.01 | -40.8 | | 26 | 70 | 120 | 0.64 | 0.64 | 0.96 | 198.13 | 0.04 | 8.31 | 0.01 | 0 | -48.58 | -44.68 | | 27 | - | 151 | 0 | 0 | 0.91 | 10000 | 0.09 | 15.37 | 0 | 0 | -70.9 | -62.89 | | 28 | - | 152 | 0 | 0 | 0.83 | 122.7 | 0.17 | 25.81 | 0 | 0 | -100.76 | -88.97 | | 29 | - | 153 | 1.61 | 0.52 | 0.95 | 6024.68 | 0.05 | 6.2 | 0.02 | 0 | -72.59 | -67.12 | | 30 | - | 154 | 1.38 | 0.71 | 0.95 | 386.75 | 0.05 | 7.55 | 0.01 | 0 | -79.67 | -75.88 | | 31 | - | 155 | 1.27 | 0 | 0.87 | 72.68 | 0.13 | 8.08 | 0.01 | 0 | -75.04 | -69.36 | | 32 | - | 156 | 0.79 | 0.35 | 0.92 | 3606.76 | 0.08 | 18.55 | 0 | 0 | -79.59 | -69 | | 33 | - | 158 | 1.03 | 0.29 | 0.89 | 411.31 | 0.11 | 26.61 | 0 | 0 | -114.14 | -95.18 | | 34 | - | 160 | 1.45 | 0 | 0.81 | 17.97 | 0.19 | 5.27 | 0.03 | 3 | -72.58 | -69.41 | | 35 | - | 161 | 0.3 | 0.3 | 0.91 | 1591.98 | 0.09 | 19.86 | 0 | 2 | -85.97 | -76.04 | | 36 | - | 162 | 0 | 0 | 0.86 | 151.13 | 0.14 | 15.92 | 0 | 2 | -88.82 | -80.99 | | 37 | - | 164 | 2.37 | 0.17 | 0.88 | 63.67 | 0.12 | 9.18 | 0 | 2 | -95.34 | -87.1 | | 38 | 75 | 165 | 0.14 | 0.09 | 0.79 | 163.94 | 0.21 | 54.1 | 0 | 29 | -357.65 | -270.93 | | 39 | - | 178 | 0 | 0 | 0.87 | 1122.11 | 0.13 | 13.39 | 0 | 2 | -34.6 | -29.13 | | 40 | 108 | 214 | 0.12 | 0.01 | 0 | 0.96 | 1 | 7.47 | 0.01 | 1 | -93.45 | -93.45 | | 41 | 321 | 459 | 0 | 0 | 0.99 | 32.23 | 0.01 | 11.92 | 0 | 1 | -20.26 | -14.75 | | 42 | 323 | 462 | 1.35 | 0 | 1 | 690.45 | 0 | 10.14 | 0 | 1 | -54.96 | -46.95 | | 43 | 324 | 467 | 0.16 | 0 | 1 | 977.07 | 0 | 18.56 | 0 | 1 | -25.57 | -15.45 | ### Main -- Describe interesting sites with SLAC? ### Main -- Alignment free analysis -- aBSREL ## Discussion ## References ## Supplementary Material

Syntax	Example	Reference
# Header	Header	基本排版
- Unordered List	Unordered List
1. Ordered List	Ordered List
- [ ] Todo List	Todo List
> Blockquote	Blockquote
Bold font	Bold font
Italics font	Italics font
~~Strikethrough~~	~~Strikethrough~~
19^th^	19^th
H~2~O	H₂O
++Inserted text++	Inserted text
==Marked text==	Marked text
[link text](https:// "title")	Link
![image alt](https:// "title")	Image
`Code`	`Code`	在筆記中貼入程式碼
```javascript var i = 0; ```	`var i = 0;`
:smile:		Emoji list
{%youtube youtube_id %}	Externals
$L^aT_eX$	L^aT_eX
:::info This is a alert area. :::	This is a alert area.