Why do we need to find and quantify distinctive features of a lineage?

Lineage-specific genes, or LSG's have received a great deal of attention in genomic studies of evolution. However, the challenge involved in assembling and annotating genomes has meant that getting accurate numbers and definitive lists has proved difficult. Nonetheless, it has been shown that "Many, but not all, lineage-specific genes can be explained by homology detection failure." Several well-known examples of lineage-specific genes have been the focus of detailed study. For instance, the loss of several functionally related genes in the yeast baker's yeast Saccharomyces cerevisiae has been linked to the loss of corresponding phenotypes. Conclusively establishing the reasons for lineage-specific genes is also troublesome. LSG's can be inferred due to loss, rapid sequence divergence, duplication of genes, or other evolutionary events. Ruling out various possibilities and disentangling the cause and effect is not always possible.

Apart from LSG's, other lineage-specific changes have been noted in cis-regulatory elements, changes in interaction partners, etc. What is the contribution of these different lineage-specific changes? Which changes have had a large role in phenotypic evolution? Are these changes correlated, and if so, in what ways? These kinds of questions regarding the relevance and implications of lineage-specific changes (LSCs) can be answered when the changes can be quantified with confidence by ruling out various bioinformatics artifacts. Once we have answers to these questions, we may begin to understand the evolution of genetic changes from a different perspective. 

Lineage-specific accumulation of repeats in genomes has also been studied, although mostly in non-genic regions. For instance, in a comparison of plant genomes, Patil et al. identified large differences in the repeat content of closely related species. Do similar changes occur in protein repeats? How rampant are such changes genome-wide? These are intriguing questions, especially when it is known that some genes have rapid changes in protein repeat content. Among the various genes that are worthy of study (GWoS), immune genes occupy the prime place. Hence, it is no wonder that Teekas et al. do a comprehensive study of protein repeat evolution in immune genes. In their article titled "Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes," they screen the annotated genomes of vertebrates for orthologs that contain protein repeats. Having identified orthologous repeats in orthologous genes, they quantify the expansion or contraction of repeats. Since these sorts of changes in repeat length seem to have a phylogenetic signal, they use PIC (Phylogenetically Independent Contrasts) to identify changes that are most distinctive in specific lineages. What if any of these changes have functional consequences will have to be seen. This approach developed by Teekas et al. opens the door for large scales identification of candidate proteins that may have "tuning knobs" of evolution. On the other hand, if these changes in repeat length have no consequence whatsoever, they reveal the regions of immune genes that are plastic to such changes.

Kantara, Dhanta Kathe: the legend of the forest

It is very rare that a Kannada movie that does not fit into a traditional genre becomes a huge hit, not just in Karnataka but across India. This is even more remarkable when the movie is not a high-budget star-studded enterprise. A folk story about the legend of the enchanted forest does have great appeal when combined with great visuals of the forest and the traditional "Bhoota Kola" dance. Although never actually stated, the movie is about the Western Ghats of India. If any forest in the world is enchanted, the Western Ghats would be the first place one would think of. As a biodiversity hotspot, the forests of the Western Ghats hold many marvelous treasures that remain hidden from humankind. 

We sequenced the genome of the Mesua Ferrea tree last year to investigate the demographic history of several forest trees. This year, we follow that up with the genome of the Wild Jack (Ayani) or Artocarpus hirsutus. Generating the genomes of forest plants by itself will not bring out the magic and lore hidden in their base pairs. Rather, interesting insights that could help us understand the adaptation of these trees to their unique habitat and how this has been achieved through changes in the genome would be of great value not only for commercial exploitation but also to sustain the forests and their diversity. In the pre-print, Patil et al. present the newly generated genome of the Wild Jack and compare its genome with that of two other species of the genus Artocarpus. By doing such comparative genomic analysis, various changes to gene sequences, as well as the complement of genes, are identified. Interestingly, it is found that the repeat content has changed drastically in the closely related commonly cultivated species Artocarpus heterophyllus (Jackfruit). Subsequently, the effect of these repeats on demographic inference is also investigated and builds upon previous work on Populus and human genomes. Nonetheless, the role of habitat is found to be more pronounced than that of repeats or the region of the genome used for the analysis. What other secrets does the enchanted forest hold? Will we ever be able to explore this forest further and what impact this will have on the forest itself are questions for tomorrow. 

Akṣhar Brahma Yog: The Yog of the Eternal God/ Immutable Consciousness or Attaining the Supreme

Chapter 8: With 28 verses or shlokas, the eighth chapter is of intermediate length (i.e.,<5%) and is mostly a monologue by Lord Bhagavan Sri Krishna, except for the first two Shlokas.

Arjuna (Shloka 2): 2 shloka

Krishna, the Supreme Personality of Godhead (Shloka 3-28): 26 shlokas

Brief Summary: In this chapter, Arjuna asks several questions, which are subsequently answered by Lord Bhagavan Sri Krishna, the supreme personality of Godhead.

Arjuna's questions are:

1. What is brahman?
2. What is the self (adhyatma)?
3. What are fruitive activities (karma)?
4. What is this material manifestation (adhibhuta)? 
5. What are the demigods (Adhidaiva)? 
6. How does the Lord of sacrifice (adhiyajna) live in the body? and in which part does he live?
7. How can those engaged in devotional service know you at the time of death?

The lord's answers are as follows:

1. Brahman: The Supreme Indestructible Entity
2. Adhyatma: one’s own self
3. Karma: fruitive activities. i.e., actions that pertain to the material personality of living beings and their development
4. Adhibhūta: the constantly changing material manifestation 
5. Adhidaiva: the universal form of the lord, which includes all the demigods
6. Adhiyajna: I, the supreme lord represented as the super soul, in the heart of every embodied being
7. Those beings who quit their body remembering Lord Sri Krishna attains Moksha. However, those engaged in other contemplations at the time of their death attain that same consciousness. Hence, with practice, one should acquire the skill of remembering the Lord at all times.

Spiritual planets can also be attained by Yogic practices. The Vedic scholars practice celibacy, chant Omkara, and remain detached from all sensual engagements. Those yogis who constantly think of me with exclusive devotion can attain me easily. These great souls who have attained me never return to this world filled with misery as they are immune to rebirth. 

All the material planets, including the Bramha planet, are subject to misery and rebirth. Only upon attaining the Lord's abode is one freed from re-birth. The time calculations are different for different planets. For instance, one day on the Bramha planet equals four yugas rotating thousand times for a human. Hence, in one Bramha day, many living entities come into being and culminate at night, and the same cycle continues. 

If one leaves the body at the auspicious time given in the Vedic literature, even accidentally will escape from the cycle of birth and death. However, for the devotees, there are no such limitations. 

Devotional service is equivalent to:

1. Studying the Vedas
2. Performing sacrifices
3. Undergoing austerities
4. Giving charity
5. Pursuing philosophical or fruitive activities

Favorite Shlokas:

Shloka 1-2:

kiṁ tad brahma kim adhyātmaṁ kiṁ karma puruṣhottama

adhibhūtaṁ cha kiṁ proktam adhidaivaṁ kim uchyate

adhiyajñaḥ kathaṁ ko ’tra dehe ’smin madhusūdana

prayāṇa-kāle cha kathaṁ jñeyo ’si niyatātmabhiḥ

Shloka 5:

anta-kāle cha mām eva smaran muktvā kalevaram

yaḥ prayāti sa mad-bhāvaṁ yāti nāstyatra sanśhayaḥ

Jñāna Vijñāna Yog: Yog through the Realization of Divine Knowledge

Chapter 7: With 30 verses or shlokas, the seventh chapter is of intermediate length (i.e.,<5%) and includes a monologue by Lord Bhagavan Sri Krishna.

Krishna, the Supreme Personality of Godhead (Shloka 1-30): 30 shlokas

Brief Summary: In this chapter, the Supreme Personality of Godhead Shree Krishna fully reveals the knowledge and wisdom after knowing that nothing else remains to be known in this world.

Among a thousand --> hardly one/few strive(s) for perfection--> Among those who have perfection, hardly one person truly knows the lord. 

Two types of energy in the lord through which all living beings are manifested:

1. Material/inferior energy= sum of (Earth, water, fire, air, space, mind, intellect, and ego).
2. Superior/soul energy= consists of embodied souls that form the basis of life in this world.

Lord Sree Krishna, the Supreme Personality of the Godhead, is analogous to the thread which holds all the beads together. Hence, the lord is the source of the entire creation into whom everything dissolves. The lord is also

1. the taste of water
2. radiance of the sun and the moon
3. sacred syllable Om in Vedic mantras
4. sound in ether
5. ability in humans
6. pure fragrance of the earth
7. brilliance in fire
8. life-force in all beings
9. penance of the ascetics
10. eternal seed of all beings
11. the intellect of the intelligent
12. the splendor of the glorious
13. the strength (devoid of desire and passion) of the strong
14. sexual activity not conflicting with virtue or scriptural injunctions

Three material states of existence/modes of Maya: goodness (sattva), passion (rajas) & ignorance (tamas).

Only by surrendering to the lord can one overcome Maya. 

Four kinds of people that don't surrender to me:

1. Those ignorant of the knowledge.
2. Those who are lazy follow their lower nature though capable of knowing me.
3. Those with deluded intellect.
4. Those with a demonic nature.

Four kinds of pious people engage in my devotion:

1. The distressed.
2. The seekers after knowledge (inquisitive).
3. The seekers of worldly possessions.
4. Those who are situated in knowledge/ seek absolute truth. (Dearest to the Lord)

We tend to pray to different deities (demigods) to fulfill our material desires as per our nature. Even these desires are taken care of due to Lord Krishna's benediction. The different deities can be considered different parts of the Lord's body.  However, the results obtained by praying to demigods are transient. The ultimate goal can be achieved by surrendering to Krishna. 

Lord Krishna has absolute knowledge of the past, present, and future.  Those who strive for liberation from the cycles of birth and death by surrendering to me realize the divine and achieve Krishna consciousness.  

Favorite Shlokas:

Shloka 7:

mattaḥ parataraṁ nānyat kiñchid asti dhanañjaya

mayi sarvam idaṁ protaṁ sūtre maṇi-gaṇā iva

Shloka 17:

teṣhāṁ jñānī nitya-yukta eka-bhaktir viśhiṣhyate

priyo hi jñānino ’tyartham ahaṁ sa cha mama priyaḥ

The ecology of influenza - role of gene loss in natural disease reservoirs

The CDC defines a reservoir of an infectious agent "as the habitat in which the agent normally lives, grows, and multiplies." When the infectious agent spills over from such a reservoir species into other susceptible species, the pathogen experiences strong selective constraints in the new host. This new environment may then select for a more potent pathogen that can spread in the new host or even across other vertebrate species. The brilliant Robert G Webster describes a lifetime of knowledge he has accumulated on this spill-over process in his talk "Influenza: Lessons learned from Pandemic H1N1" at Columbia University. This talk, now more than a decade old, has some interesting discussion at the end that, in hindsight, now after the covid pandemic looks intriguing. 

The most interesting part of the talk for me is when he talks about birds. First, he mentions that shorebirds (Charadriiformes) such as the Ruddy Turnstone (Arenaria interpres), Semipalmated Sandpiper (Calidris pusilla), Sanderling (Calidris alba), European herring gull (Larus argentatus), laughing gull (Leucophaeus atricilla), and Red knot (Calidris canutus) and waterfowl (Anseriformes) species such as mallard or wild duck (Anas platyrhynchos) and pintail or northern pintail (Anas acuta) are some of the migratory birds that are monitored for influenza in North America. The second time he mentions birds is when he explains the difference between Ducks and Chicken and how the RIG-I gene is lost in chickens. RIG-I is an immune sensor that activates the production of interferon-Beta. A more detailed talk that focuses on the loss of this gene and how the discovery was made is explained by Katherine Magor of the University of Alberta in her talk titled "How ducks survive the flu; the secrets of the reservoir host." 

It has been more than a decade since the paper describing the lack of RIG-I in chicken and "Association of RIG-I with innate immunity of ducks to influenza" has been published. In this decade, it has been established that the "Loss of RIG-I leads to a functional replacement with MDA5 in the Chinese tree shrew". Although a paper (from fish immunologist Chris Secombes) looking at the "Origin and evolution of the RIG-I like RNA helicase gene family" claimed that "Unlike RIG-I, whose presence in chicken and some fish species is uncertain..", it did not conclusively establish the lack of RIG-I in chicken. Limitations in genome assembly quality and availability of large genomic datasets can be blamed for these uncertainties. Notably, the paper by Secombes also investigates the origin of RIG-I and related genes through gene fusion, domain duplication, and deletion and follows in the line of a previous paper titled "Evolution of MDA-5/RIG-I-dependent innate immunity: Independent evolution by domain grafting".

The birth and death of the genes from the terminal complement pathway are surprisingly similar to the history of the RIG-I-like RNA helicase gene family. Domain fusion events are involved in the birth of both gene families at the boundary of invertebrates and vertebrates, both RIG-I and C9 are lost in Galliform birds but are present in Anseriform birds and both are involved in the immune response. Finally, our manuscript dealing with the Birth and Death in the Terminal Complement Pathway is published.

 

Dhyān Yog: The Yog of Meditation also known as the Atma-Samyama Yoga

Chapter 6: With 47 verses or shlokas, the sixth chapter is of the same length as the first chapter. 

Arjuna (Shloka 33-34, 37-39): 5 shlokas

Krishna, the Supreme Personality of Godhead (Shloka 1-32, 35-36, 40-47): 42 shlokas

Brief Summary: In this chapter, the lord explains the Dhyan Yog aspect as a continuation of his answer to prince Arjuna in the previous chapter.

Sanyāsīs=yogis=who perform prescribed duties without desiring the results of their actions, is free from feelings of possessiveness, lives in seclusion, and engage the body, mind, and self in a relationship with the supreme.

Shloka 5-6: The mind can be your friend if you have conquered it, but it can also be your worst enemy if you have failed to conquer your mind. 

Free from Dualities: Cold and heat, Joy and sorrow, honor and dishonor, happiness and distress

For the satisfied yogi who is in KC, 

• Shloka 8: Dirt=stones=gold
• Shloka 9: Well-wishers=friends=foe=pious=sinners=affectionate=benefactors=envious=neutral =mediators. Notably, this shloka lacks a purport. 

Shloka 11-12 are very specific in detail regarding the pre-requisites for meditation. The specifics are:

1. Should be performed in a sacred/secluded place. A list of sacred places is mentioned in the purport and includes Prayag, Mathura, Brindavan, Rishikesh, and Haridwar.
2. Kusha/Kusa grass (Desmostachya bipinnata) should be covered with deerskin and a soft cloth to prepare a seat.
3. The seat should be at optimum height, i.e., neither too high nor too low.

Shloka 13-14: The sitting position requires the alignment of the body, neck, and head in a straight line. One should focus on the tip of the nose and meditate upon the divine within the heart.

Yoga is not a mere physical exercise, rather it is a means to attain the abode of the lord (AOL). The importance of proper sleep and a healthy diet are explained concerning becoming a perfect yogi. Discipline in the lifestyle can mitigate all material pains, one has to follow the correct schedule for habits of eating, sleeping, recreation, and work in day-to-day life.

The flickering nature of the mind can be controlled by the practice of yoga which can lead to the attainment of trance or "samadhi.". In the stage of samadhi, the person is engrossed in self and attains the highest form of happiness, and is unaffected by the miseries of the material world. 

Arjuna questions the knowledge imparted by Lord Krishna regarding yoga as impractical and unendurable. Characters of the mind described by the prince Arjuna:

• Restless
• Turbulent
• Strong
• Obstinate
• More difficult to control than the wind

Lord: practice & detachment. Possible for those who have learned to control the mind.

Arjuna further enquires what happens to the unsuccessful yogi who cannot reach his goal due to an unsteady mind. Would such a person miss out on both material enjoyment and spiritual success? 

The lord reassures Arjuna as follows:

• Those who strive for KC are never overcome by evil.
• Unsuccessful yogi attains the abode of the virtuous (AOV) upon death. After dwelling in AOV for many ages, such a yogi is reborn in the family of pious and prosperous people.
• Else, if a yogi has developed dispassion through long practice of yoga, such a yogi is reborn in the family endowed with divine wisdom.
• Following rebirth, the yogi strives for liberation with even greater earnestness by reawakening the wisdom of past lives. 

Shloka 46: yogi > tapasvī (ascetic) ; yogi > jñānī (a person of learning); yogi > karmī (ritualistic performer)

The results of spiritual practices are accumulated and passed to the next birth. Hence, even the unsuccessful yogi is making progress and eventually attains liberation. In the last shloka, lord Krishna highlighted the importance of surrendering oneself to the divine with utmost faith and love becoming the highest yogi.

Favorite Shlokas:

Shloka 5:

uddhared ātmanātmānaṁ nātmānam avasādayet

ātmaiva hyātmano bandhur ātmaiva ripur ātmanaḥ

Shloka 16:

nātyaśhnatastu yogo ’sti na chaikāntam anaśhnataḥ

na chāti-svapna-śhīlasya jāgrato naiva chārjuna

Karm Sanyās Yoga: The Yog of Renunciation

Chapter 5: With 29 verses or shlokas, the fifth chapter is one of the shorter chapters. 

Arjuna (Shloka 1): 1 shloka

Krishna, the Supreme Personality of Godhead (Shloka 2-29): 28 shlokas

Brief Summary: In this chapter, Lord Krishna responds to prince Arjun's question about whether the path of renunciation of action or working with devotion is better.

The Lord reassures the prince that both paths lead to the supreme goal. Yet, he notes that working with devotion is easier/better than the renunciation of action. Then the lord proceeds to explain that both renunciation of action and devotional action are the same. The Krishna conscious person is a pure soul who controls his mind and senses, being dear to everyone. 

Shloka 10 mentions the analogy of "Padma-patram iva āmbhasā" (which means like water on a lotus leaf) to reiterate that those who perform actions by abandoning all attachments are unaffected by sin just like a lotus leaf which remains untouched by water. The 13th shloka refers to the human body as a city of 9 gates in which the soul resides happily through self-control and detachment.

Shloka 5.18: For the truly learned, Brahmin=cow=elephant=dog=dog eater as the same consciousness resides in all.  

Krishna conscious person (KCP),

1. Has equanimity (i.e., neither rejoices upon success nor laments upon failure or unpleasantness) of mind. The famous poet Hari Vansh Rai Bachan is credited with saying "Man ka ho to acha, na ho to aur bi acha.".This means that if things happen according to your wishes it is good, it is even better if they don't. The sense of equanimity and the importance of surrendering to the divine is exemplified by this statement.
2. Knows the divinity within all beings.
3. Enjoys unlimited happiness.
4. Is free from fear, anger and material desires.
5. Is self-realised and self-disciplined
6. Conquer the cycle of birth and death in this very life.

Shlokas 27-28 emphasise the role of meditation for the liberation of the soul, with the help of breath control. Meditation can also be attained by concentrating between the eyebrows thereby liberating us from desires, fear and anger. 

Favourite Shlokas:

Shloka 10:

brahmaṇyādhāya karmāṇi saṅgaṁ tyaktvā karoti yaḥ

lipyate na sa pāpena padma-patram ivāmbhasā

Sholkas 27-28: 

sparśhān kṛitvā bahir bāhyānśh chakṣhuśh chaivāntare bhruvoḥ

prāṇāpānau samau kṛitvā nāsābhyantara-chāriṇau

yatendriya-mano-buddhir munir mokṣha-parāyaṇaḥ

vigatechchhā-bhaya-krodho yaḥ sadā mukta eva saḥ